YOUR TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA MALAYSIA DECEMBER 2020

Highlights from AASLD,

IDWeek, ASN, TCT
& HIV Glasgow 2020

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CONTENTS
MIMS DOCTOR - YOUR TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA CEO
Yasunobu Sakai

Country Vice President

(Marketing Platform & Medcomms)
Aundrey Yeoh

DECEMBER ISSUE Senior Editor

Saras Ramiya

Associate Editor
Malaysia Focus Pank Jit Sin
4 Diabetes burnout a stark reality of diabetes in Malaysia
Contributing Editors
Hong Kong: Christina Lau
6 NGO, pharma stakeholder launches campaign for prediabetes awareness and Malaysia: Rachel Soon
action Singapore: Elvira Manzano, Audrey Abella,
Roshini Claire Anthony, Pearl Toh,
Dr Margaret Shi, Natalia Reoutova
8 Medication use in lactation: Evaluating safety concerns Philippines: Stephen Padilla, Jairia Dela
Cruz, Elaine Soliven
10 Hexavalent, pneumococcal vaccine update included in national immunisation
Designers
schedule Razli Rahman, Tina Ng,
Peggy Tio, Sam Shum
12 Genetic screening in Asian oral cancer cells reveals new targets
Production
Raymond Choo, Ronald Chew Khoy Lun
14 New biologic enters fight against psoriasis
Circulation Executive
Pauline Hoe

Finance Manager
Jessie Seow

Advertising Coordinator
Raymond Choo

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16 1st COVID-19 vaccine coming soon
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20 HBV suppressed on long-term tenofovir alafenamide; switch from TDF
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20 24

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DOCTOR | DECEMBER ISSUE
 DEAR DOCTOR,
NOTE FROM THE TEAM I hope you enjoy reading articles in MIMS Doctor and find the knowledge
useful in your clinical practice. With more medical updates coming up in
2021, I look forward to bringing you updated content in MIMS Doctor.

Also, feel free to participate in the online CPD modules via MIMS eLearning
platform to obtain your CPD points from the comfort of your home or clinic.

Saras Ramiya I wish you a healthy, happy and prosperous new year!

DEAR DOCTOR,
It’s been a challenging year with many changes. As the COVID-19 vaccines
become available, I hope a little of the old normal becomes the new normal
again. I’d like to thank our readers for your continued readership and trust.

On a personal note, I’ve noticed that since the MCO began and strict
mask-wearing was enforced, I have not come down with a single case of
cold or cough. It may be premature to hazard a guess without any scientific
evidence, but perhaps this is due to the double whammy of increased Pank Jit Sin
hand hygiene and mask-wearing. Have you seen any change in patient
complaints? We would love to hear from you.

In the words of the great Spock, Live long and prosper!

DEAR DOCTOR,
Thank you for your continued support of MIMS Doctor and our associated
publications. We hope that our medical updates have proved useful or
encouraging to you in the face of the unprecedented challenges of 2020.

As the new year approaches with prospects of a working COVID-19 vaccine

and life returning to normal, we wish you continued good health and spirits.

Rachel Soon Stay safe, and may you have a happier 2021!

DEAR DOCTOR,
We stood up against this challenging 2020 all thanks to you, our dear
doctors and frontliners. Your determination and sacrifice in battling our
invisible enemy are highly appreciated and we are forever thankful for your
strength and braveness. May MIMS Doctor continue to be your literature
companion in your expedition towards a better healthcare community.

Happy new year and thanks for inspiring us in battling COVID-19!

Razli Rahman
CONTENTS
MIMS DOCTOR - YOUR TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA Philippines
Wilma Calderon, Gracia Cruz, Dr Ryan
Cua, Noriel Escueta, Ned Manalili, Marvin
Osea, Richard Rivera, Michelle Teodoro
Tel: (632) 886 0333
Email: enquiry.ph@mims.com

Singapore
DECEMBER ISSUE Melanie Chia, Jasmine Tan, Kerwin Tan,
Warren Tan, Janice Tan, Jackson Tu
Tel: (65) 6290 7462
Email: enquiry.sg@mims.com
25 TAF during pregnancy curbs HBV transmission from mother to child
Thailand
Nawiya Witayarithipakorn
Infectious Disease (IDWeek 2020) Virtual Conference, October 21-25 Tel: (662) 741 5354
Email: enquiry.th@mims.com
30 Asymptomatic COVID-19 individuals carry similar viral loads as symptomatic
patients Vietnam
Nguyen Thi Lan Huong,
Nguyen Thi My Dung
31 Face shield minimizes SARS-CoV-2 spread, hospital-acquired infections Tel: (848) 3829 7923
Email: enquiry.vn@mims.com

32 Chlorhexidine oral rinse improves COPD symptoms

33 Echinocandins boost the antifungal armamentarium MIMS Doctor is published 12 times a year
in Malaysia by MIMS Medica, a division of
MIMS. MIMS Doctor is a controlled circulation
38 Oral sulopenem shows promise for uncomplicated UTI publication to medical practitioners in
Asia. Editorial matter published herein has
been prepared by professional editorial
staff. Views expressed are not necessarily
those of MIMS. Although great effort has
been made in compiling and checking the
information given in this publication to
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31 38 negligence or otherwise howsoever, or for
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American Society of Nephrology (ASN) Kidney Week 2020, October 20-25 for patent ownership or patent legality of any
39 Icosapent ethyl shows consistent benefit in statin-treated patients medical product mentioned or featured, nor
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or originality of the product which, therein
40 More protein of no help to haemodialysis patients? infringes upon the intellectual property
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not mean that the publisher advocates
or rejects its use either generally or in any
42 Metformin may have CV benefits in CKD patients with MetS particular field or fields. The information
contained within should not be relied
upon solely for final treatment decisions.
Transcatheter Cardiovascular Therapeutics (TCT) Connect 2020,
October 14-18
46 Shorter DAPT okay in high bleeding risk patients post-PCI

48 NACMI registry IDs key traits, risks in patients with COVID-19 and ST-elevation

40 46

2
DOCTOR | DECEMBER ISSUE
CONTENTS
MIMS DOCTOR - YOUR TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA ©2020 MIMS. All rights reserved. No part
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DECEMBER ISSUE of the copyright owner. Permission
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HIV Glasgow 2020 Virtual Meeting, October 5-8 Entered as second-class mail at the Makati
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63 Humour

64 Calendar PP17111/07/2017(034752) ISSN 2410-7808

54 57

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3
DOCTOR | DECEMBER ISSUE
 MALAYSIA FOCUS

Diabetes burnout a stark reality of diabetes

in Malaysia
PANK JIT SIN

D
iabetes burnout, a state of
emotional or physical exhaus-
tion as a result of frustration
and being overwhelmed by the burden
of diabetes self-management, occurs
in 96 percent of diabetes sufferers in
Malaysia, a survey shows.

“Stress can affect

diabetes control,
therefore managing
the emotional and
psychological state is as
important as managing
glucose readings.”

According to the survey done on

158 respondents, most want to be problem among Malaysians living with includes a dietitian can assist people
empowered over their diet. The survey diabetes. This is partly due to the fact with diabetes learn how to eat well
by Abbott aimed to better understand that many lack knowledge on how with less stress and better manage
the challenges faced by those living dietary behaviour and slight chang- their diabetes. Chee is professor in the
with diabetes and to arrive at ways to es in their eating plan can negatively Department of Nutrition and Dietetics,
empower patients. Diabetes burnout impact diabetes management. She International Medical University.
has been shown to lead to poor adher- said: “Therefore, keeping blood glu-
ence, reduced self-care and poor glu- cose levels on target can prevent or Additionally, the survey showed
cose control among persons with dia- delay the onset of complications such that respondents wanted to be more
betes. More than 75 percent of survey as blindness, kidney disease, and empowered over their diet, ideally with
respondents said that maintaining a heart disease.” solutions that help reduce the stress
healthy weight and following a healthy of following a diabetes-specific diet.
diet were their two main stressors. The Echoing Norlaila’s view, Dr Winnie The two solutions respondents found
respondents reported that they faced Chee, Ph.D, said: “Stress can affect to be most useful were convenient and
most problems in the following areas: diabetes control, therefore managing affordable diabetes-friendly meals (88
72 percent reported having problems the emotional and psychological state percent) and diabetes-specific sup-
abiding by a diet suitable for people is as important as managing glucose plements to replace meals or snacks
with diabetes while 73 percent report- readings. People with diabetes are (91 percent). In such an instance, “di-
ed having problems keeping count of often burdened by many aspects of abetes-specific formulas are a sim-
calories or carbohydrates daily. self-care, particularly dietary choices. ple and convenient solution to help
Knowing the right foods to eat that will those living with diabetes adjust their
Commenting on the topic, Asso- not raise their blood sugar, is a formi- lifestyle," said Dr Nina Mazera Mohd
ciate Professor Dr Norlaila Mustafa, dable challenge for most individuals.” Said, medical director, Abbott Nutrition
consultant physician and endocrinolo- She added that diet control plays a Malaysia, adding that the company
gist, Hospital Canselor Tuanku Muhriz key role in managing diabetes and has over 3 decades of experience de-
Universiti Kebangsaan Malaysia, delaying complications, hence a mul- veloping nutrition formulas for persons
said poor glucose control is a major tidisciplinary healthcare team which with diabetes.

4
DOCTOR | DECEMBER ISSUE
 MALAYSIA FOCUS

NGO, pharma stakeholder launches

campaign for prediabetes awareness
and action
PANK JIT SIN by answering a simple questionnaire affects one-in-five Malaysians. [Avail-

D
regarding their physical wellbeing able at http://iku.moh.gov.my/im-
iabetes Malaysia, a non-profit, and lifestyle choices. Also, the web- ages/IKU/Document/REPORT/
non-governmental organization site contains articles that break down NHMS2019/Infographic_Booklet_
has partnered with Merck Ma- popular myths about prediabetes and NHMS_2019-English.pdf Accessed
laysia to launch a campaign aimed at explain the health complications asso- on 12 November] This number was
raising awareness of prediabetes and ciated with it. More information can be projected to be reached in 2045 ac-
to facilitate earlier action against it. found at letsmakeachange.my. cording to the International Diabetes
Federation (IDF) Atlas. As a nation,
Aptly named ‘Let’s Make A Malaysia arrived at the diabetes rate
Change,’ the campaign hopes that “As a nation, projection by more than 2 decades
through increased conversation about earlier. [Available at https://www.dia-
prediabetes, Malaysians can take
Malaysia arrived at betesatlas.org/data/en/country/120/
action on the condition earlier and the diabetes rate my.html Accessed on 12 November]
delay or prevent the onset of type 2 projection by more
diabetes. Driving the campaign will be than 2 decades The bulk of patients suffer from
a website dedicated to prediabetes. type 2 diabetes and they start out
Here, a diabetes risk calculator and
earlier.” with prediabetes, which is essential-
various information are available for ly having blood glucose levels that
better understanding of prediabetes are higher than normal, but not quite
and the consequences for those who According to the most recent Na- high enough to be considered dia-
are at risk. tional Health and Morbidity Survey betic. Interestingly, on top of increas-
(NHMS) 2019, noncommunicable ing the risk of developing full-blown
The risk calculator allows users diseases, especially diabetes, are on diabetes, prediabetes may also lead
to determine their risk of prediabetes the rise in Malaysia. Diabetes already to other potential health problems

6
DOCTOR | DECEMBER ISSUE
 MALAYSIA FOCUS

such as complications in the heart, thirsty, excessive urination and blurry

eyes and kidneys, which are hallmarks vision, could also manifest itself while “The best way to
of diabetes. [Available at https://www. still in the prediabetic stage.
cdc.gov/diabetes/library/features/
determine if someone
truth-about-prediabetes.html?CDC_ “Malaysia ranks very highly in Asia has prediabetes is
AA_refVal=https%3A%2F%2Fwww. in terms of number of patients suf- through a blood test
cdc.gov%2Ffeatures%2Fdiabetespre- fering from diabetes,” said Professor to determine their
vention%2Findex.html Accessed Dato’ Dr Ikram Shah Ismail, president
on 12 November] In fact, those with of Diabetes Malaysia. He added: “Here
glucose levels.”
prediabetes can experience exten- at Diabetes Malaysia, we fully under-
sive kidney damage, much like those stand how challenging it may be to live
with diagnosed diabetes. [Available with or care for someone with diabe- By the time of diagnosis, it was
at https://www.kidney.org/news/kid- tes. It is better to tackle the disease already too late, and they now take
neyCare/Summer10/PreDiabetes Ac- when it is still in the prediabetic stage, medication for the rest of their lives.
cessed on 12 November] particularly if it is detected early. De- He said: “I would encourage those
pending on the patient, diabetes may who are at high risk of diabetes to get
The latest data from IDF indicates not be preventable, but treating predi- themselves checked and if they have
that the prevalence of impaired glucose abetes offers an opportunity to at least prediabetes, to speak to their doctors
tolerance (IGT)—used to identify predi- delay it.” He advised at-risk persons to about what they can do to manage
abetes—is 15.5 percent and affects be aware and take charge of their con- their condition.”
3,398.9 million adults aged 20–79. dition before it gets worse.
Christoph Hamann, president and
Symptoms of prediabetes may not Dr Alexander Tan, consultant en- managing director of Merck Malaysia,
be obvious for the most part. A person docrinologist, said most of the pa- was also present at the launch of the
may be prediabetic without realizing it. tients he encountered with diabetes campaign.
The best way to determine if someone only started being proactive about
has prediabetes is through a blood their condition after they were diag-
test to determine their glucose levels. nosed, possibly because they were Scan
the QR code
not aware of their prediabetes state for more
That said, some of the symptoms or underestimated the seriousness of information.
for diabetes such as frequently feeling their condition.

7
DOCTOR | DECEMBER ISSUE
 MALAYSIA FOCUS

Medication use in lactation:

Evaluating safety concerns
RACHEL SOON / medication in breastfeeding such as
SHARMILA SATHIANATHAN Gomella’s Neonatology (Lange Med-
ical Books/McGraw-Hill Education).
Breastfeeding and medica- Quick references may be sought from
tion can often be a concern- drug information databases such as
ing combination for mothers, Lexicomp’s breastfeeding section for
due to the possible impacts of detailed descriptions on medications.
drug diffusion through mater-
nal milk. MIMS Doctor received According to the US Centers for
feedback from Sharmila Sath- Disease Control and Prevention (CDC)
ianathan, neonatal intensive and the American Academy of Pedi- HCPs may be able to alleviate their
care unit (NICU) pharmacist at atrics (AAP), necessary considerations anxiety as well as prevent nonadher-
Hospital Tengku Ampuan Rahi- include the mother’s medication use, ence to medication and/ or breast-
mah, Klang, on considerations effects of medication consumption on feeding discontinuation.
for medication safety in breast- breast milk production levels, amount
feeding mothers. The follow- of medication content in breast milk, What affects medication concen-
ing is an edited version of her the child’s age, amount of breast milk tration in breast milk?
commentary on the issue. consumed, amount of medication ab-
• Molecular size of medication.

A
sorbed orally by the child, and poten- Drugs with higher molecular weight
s a pharmacist, I receive fre- tial side effects from the medication. enter milk in lower concentrations.
quent enquiries from health- [Available at: https://www.cdc.gov/ • Degree of ionisation. Milk is more
care professionals (HCPs) and breastfeeding/breastfeeding-spe- acidic (pH 7.2) than mother’s plasma
(pH 7.4). Milk attracts weak organic
patients on the safety of medications cial-circumstances/vaccinations-med-
bases, which become ionised and
consumed during lactation. As many ications-drugs/prescription-medica- ‘trapped,’ hence causing their higher
are fearful of the effects of a medica- tion-use.html] concentration in milk.
tion towards a child, some choose • Maternal plasma concentration.
the easier option of stopping lacta- In general, HCPs should opt for Medications with higher volume of
distribution are less concentrated in
tion while consuming medications in drugs with a short half-life and the low-
maternal plasma and hence in milk.
general. This is not only wrong, but it est effective dose while breastfeeding. • Maternal plasma protein binding.
prevents a child from receiving optimal Drugs with higher protein-binding
nutrition from breast milk. An article by Neil Hotham and Eliz- properties circulate in lower free
abeth Hotham published in Australian molecule concentrations, and thus
diffuse into milk at lower concentra-
HCPs can refer to resources such Prescriber highlighted several medica-
tions.
as the Drugs and Lactation Database tions contraindicated to breastfeeding
(LactMed®)—part of the US National including amiodarone, antineoplastics, What affects adverse effect risk
Library of Medicine (NLM) Toxicology gold salts, iodine, lithium, radiophar- towards breastfeeding infants?
Data Network—which is a database maceuticals, and oral retinoids. Other • Timing of medication administration.
on the safety of medication consump- key points are summarized in Table • Toxicity; some medications require
tion during breastfeeding and is ref- 1 [Aust Prescr 2015;38(5):156–159; monitoring due to drug accumula-
erenced from scientific literature. The 2016;39(1):27 (published correction)] tion.
• Extent of oral bioavailability.
database provides information on safe
• Volume of breast milk taken by
levels (if any) of medication content To conclude, many medications infant.
in infant blood, adverse effects, alter- consumed by mothers are safe with • Relative Infant Dose (RID). An RID
native medication suggestions, and breastfeeding as the amount excret- <10 percent is generally safe.
monitoring parameters. ed into the breast milk is small. HCPs • Age of infant; children <2 months
old may be at higher risk of adverse
can refer to a wide range of resources
effects.
Besides that, one can refer to to ensure medication safety prior to
books on neonatal medicine that advising mothers. By sharing the ev- Table 1. Key points to consider in medication
provide information on safety of idence from literature with mothers, use during lactation.

8
DOCTOR | DECEMBER ISSUE
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E W Current evidence and the international

N advisory on the use of ibuprofen

n to access
The efficacy, safety and cost-effectiveness of ibuprofen are well
established. Ibuprofen is listed as an ‘Essential Medicine’ by the
World Health Organization. The recent outbreak of COVID-19 has

S ca
raised concerns about the potential harm associated with the use
of ibuprofen. This module provides updated information on the
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E W Rotavirus: An overview
N

n to access
Rotavirus is the leading cause of severe gastroenteritis in infants
and children aged younger than 5 years, and represents a growing
healthcare burden in developing countries. This online CPD video
provides healthcare professionals with the practical knowledge on

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Seasonal influenza : A comprehensive overview

n to access

Influenza or “the flu” is an acute respiratory infection typically

caused by influenza viruses that can occur in local outbreaks and
seasonal epidemics. The clinical presentation of influenza illness
varies from asymptomatic infection to severe. Vaccination is the
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most effective method for the prevention and control of influenza,

as well as in reducing the burden associated with influenza.

Managing haemorrhoids in primary care:

A focus on medical therapy
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At least two-thirds of Malaysian adults will experience

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patients are embarrassed to seek medical advice until their
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 MALAYSIA FOCUS

Hexavalent, pneumococcal vaccine

update included in national immunisation
schedule
RACHEL SOON / introduction of the hexavalent vaccine 2020, with immunisation schedules
SARAS RAMIYA into the NIP was made after careful adjusted for those already aged 5

T
consideration by the National Immuni- months and above.
he Malaysian National Immuni- sation Policy and Practice Committee,
sation Programme (NIP) will now and improves Malaysia’s public vacci- “Implementation [of the hexavalent
include a hexavalent combina- nation programme to align with those vaccine] will be conducted in stages,
tion DTaP-IPV-HiB-HepB vaccine and adopted by 49 other countries. which will start as early as November
a pneumococcal vaccine. 2020 depending on the availability of
“[With the updated schedule], this vaccine supply at MOH health fa-
Previously only available in private only four doses of [combination] vac- cilities,” said Director-General of Health
healthcare settings, the hexavalent cine are required for each child,” said Tan Sri Dato’ Seri Dr Noor Hisham Ab-
vaccine adds hepatitis B booster shots Jamiatul. “Meanwhile, a separate hep- dullah in a recent press statement.
to the previous pentavalent DTaP-IPV- atitis B vaccine should only be given
Hib (diphtheria, tetanus, polio, pertus- as one injection after birth. This means On the PCV10 vaccine, Noor Hish-
sis, and Haemophilus influenzae B) that the number of injections is re- am added that it would be available
combination. duced to five to prevent six diseases.” beginning 1 December 2020 and will
be included in the NIP for 2 years.
The newly added 10-valent The MOH published a new immu-
pneumococcal conjugate vaccine nisation schedule factoring both up- Commenting on the update, Dr
(PCV10) is indicated to prevent pneu- dates to the NIP. Under the previous Rozita Ab Rahman, senior principal
monia and invasive pneumococcal schedule, the DTaP-IPV-Hib vaccine assistant director, MOH Family Health
disease caused by Streptococcus was administered in four doses at 2, Development Division, added that the
pneumoniae (serotypes 1, 4, 5, 6B, 3, 5, and 18 months of age, while the replacement of the pentavalent com-
7F, 9V, 14, 18C, 19F, and 23F). PCV10 hepatitis B vaccine was administered bination with the hexavalent version
also induces antibody response to separately as three doses at birth, and would reduce the number of neces-
serotypes 6A and 19A. [Available at: at 1 and 6 months of age, making a sary health clinic visits for a child and
https://www.who.int/immunization/ total of seven injections to cover the their caretakers.
policy/position_papers/who_pp_ same six diseases.
pcv_2019_summary.pdf?ua=1] “The second advantage is from
The PCV10 is scheduled as three the point of view of the comfort of
According to Dr Jamiatul Aida Md doses to be given at ages 4, 6, and the baby itself. Injections are painful
Sani, senior principal assistant director, 15 months, and is available to chil- for babies, even for a moment. Less
MOH’s Disease Control Division, the dren born on and after 1 January injections means less episodes of
pain and crying,” said Rozita. “Thirdly,
healthcare personnel will have more
time during clinic appointments to
conduct assessments of the babies’
health and development, such as
their growth, and sensory and intellec-
tual development.”

Introduced in the 1950s by the

MOH to curb infectious diseases, the
NIP has undergone several updates
since its inception, such as the ad-
dition of hepatitis B in 1989, Hib and
MMR in 2002, and the pentavalent

10
DOCTOR | DECEMBER ISSUE
 MALAYSIA FOCUS

DTAP-IPV-Hib in 2008, following rec- children, said consultant paediatrician “In Malaysia, a vaccine goes
ommendations from the World Health and Immunise4Life chairman Datuk Dr through a strict and thorough regis-
Organization (WHO). Zulkifli Ismail. tration process by the Drug Control
Authority (DCA) under the MOH,”
The current full vaccination sched- "I have been giving this vaccine to said Norleen. “After the approval for
ule covers 13 diseases including tu- [infants] and children in private health registration is granted, only then can
berculosis, hepatitis B, diphtheria, facilities for many years," said Zulki- the vaccine be used and marketed in
tetanus, whooping cough (pertussis), fli, who welcomed the changes to Malaysia, including being introduced in
polio, Hib, measles, mumps, rubella, the NIP. He shared that in his experi- the NIP.”
Japanese encephalitis (JE), pneumo- ence, infants might cry for a while af-
coccal disease, and human papilloma ter receiving the injection, but this was Currently, two hexavalent vaccines
virus (HPV)-induced cancer. normal and could be alleviated with are registered in Malaysia and have
breastfeeding and persuasion. been in use in private healthcare fa-
All vaccines are initially adminis- cilities since 2006 and 2013. Most
tered within 2 years from birth, except "Other mild side effects include ir- adverse effects following immunisa-
for the HPV vaccine, which is admin- ritation, pain and redness at the injec- tion (AEFI) reported for the NIP’s new
istered to teenage girls at 13 years of tion site. Most babies do not show any hexavalent vaccine are mild and can
age. Booster doses for MMR, DTaP, reaction at all,” Zulkifli added. be resolved within a few days with or
and tetanus are also given during without treatment, she said.
school-attending ages. Adding to this, Norleen Mohamed
Ali, senior principal assistant director “The pattern of reported AEFI
Addressing vaccine safety of the Pharmacovigilance Section at [for this vaccine] are similar to other
concerns the National Pharmaceutical Regula- vaccines. Serious AEFI can still oc-
With regards to the potential for vac- tory Agency (NPRA), said that parents cur, but their frequency is rare,” said
cine hesitancy, especially towards a can be assured the hexavalent vac- Norleen. “Parents are encouraged
wider-ranging combination, healthcare cine is safe to use and has undergone to report AEFI experienced by their
professionals can assure parents and multiple clinical trial phases prior to [children], even if it is a mild reaction
caretakers that the vaccine has long commercial use to ensure its efficacy such as fever, swelling or itching at the
been safely administered to young and safety. injection site.”

Norleen added that the NPRA con-

stantly and actively monitors all vac-
cines in Malaysia, and that any AEFI
either mild or serious, can be reported
through healthcare providers or direct-
ly to the NPRA. NPRA reports can be
lodged through the NPRA’s website at
www.npra.gov.my by clicking on the
‘Consumer’ tab and selecting ‘Con-
SERF Online Reporting.’

Norleen stressed the safety of the

hexavalent vaccine added to the NIP,
saying, ‟The benefit of the vaccination
to prevent the disease is higher com-
The new National Immunisation Schedule for Children as issued by the MOH commencing No- pared to the risk of AEFI, which are
vember 2020. (Image credit: Immunise4Life) mostly mild and harmless.”

Eds: This article was written from a statement issued by Immunise4Life, a community education programme launched in
collaboration with the MOH, Malaysian Paediatric Association (MPA), and Malaysian Society of Infectious Diseases and
Chemotherapy (MSIDC). The programme aims to promote immunisation for all ages against vaccine-preventable diseases.
More information and resources for patient education are available at www.immunise4life.my.

11
DOCTOR | DECEMBER ISSUE
 MALAYSIA FOCUS

Genetic screening in Asian oral cancer

cells reveals new targets
PANK JIT SIN “Notably, we showed that about 5 author and senior group leader of

N
percent (45/918) of these genes are CRM’s Head and Neck Cancer Re-
ew genetic targets for im- highly tractable with approved drugs, search Team, the study marks a pio-
proved treatment of oral squa- or have drugs that are in late-stage neering attempt at employing CRIS-
mous cell carcinomas (OSCCs) of clinical testing, demonstrating that PR-Cas9 gene editing tools in oral
have been identified by Malaysian these screens could help to prioritize cancer research.
scientists using cutting-edge screen- drugs that could be repurposed for
ing technologies. OSCC treatment,” said the authors. “Using [CRISPR-Cas9], we were
able to sift through tens of thou-
Using the CRISPR-Cas9 gene ed- Results from the study showed sands of genes to identify the handful
iting tool, researchers from the Head that many previously identified OS- that cause oral cancer cells to grow.
and Neck Cancer Research Team at CC-related cancer genes were likely These handful of genes are now the
Cancer Research Malaysia (CRM) non-essential to the cancer’s surviv- top list for the development of target-
conducted genome-wide screens on ability, and thus might have limited ed treatment … that kills cancer cells
21 OSCC cell lines, 14 of which were therapeutic value. while sparing normal healthy cells,”
derived from tumours of Malaysian pa- said Cheong.
tients with OSCC. On the other hand, potentially im-
pactful new targets were identified, “Oral cancer is more common in
The team successfully identi- including the paralogous genes YAP1 Asia and is the most common cause of
fied 918 genes associated with the and WWTR1 of the Hippo signalling cancer-related deaths in men in India,”
improved survival of cancer cells in pathway.The team found that cell lines said Professor Datin Paduka Dr Teo
OSCC, including some already under where either of the two were impaired Soo Hwang, OBE, CRM chief scien-
investigation for OSCC or other can- created a detrimental loss-of-fitness tific officer. “As we move into an era of
cers (CDK6, PIK3CA, FGFR1), as well effect on the cancer cells. precision medicine, we have reached
as novel genes that have yet to be ex- a turning point where we can now
plored as potential therapeutic targets. “YAP1 or WWTR1 amplifications use powerful technologies to develop
[eLife 2020;9:e57761] occur in approximately 19 percent more effective cancer therapies.”
of head and neck squamous cell
carcinomas (YAP1: 5.5 percent, The study was conducted in col-
WWTR1: 14.3 percent), which puts laboration with cancer genomics ex-
[them] among the top five cancers perts Professor Dr Mathew Garnett
with the highest amplification of these and (formerly) Dr Ultan McDermott of
genes amongst 33 cancer types,” said the Wellcome Sanger Institute, UK.
the authors.
“With this gene editing technology,
The study also found that cancer- we were able to dissect the function
ous cells from patients with a history of cancer genes. Next, the team will
of betel quid chewing showed unique leverage on these findings to conduct
gene dependencies, such as in the high-throughput testing of hundreds of
nuclear factor-κB (NF-κB) signalling anti-cancer drugs,” said Garnett, who
pathway, that did not appear in cell also co-led the study.
lines derived from Caucasian or Asian
patients who were not known to chew “We are delighted that through
betel quid. the collaboration with CRM and the
Wellcome Sanger Institute, we may
Pioneering research among be able to amplify treatment op-
Asian populations tions for oral cancer, especially for
According to Professor Dr Cheong Asians [among whom] most cases
Professor Dr Cheong Sok Ching Sok Ching, corresponding study are diagnosed.”

12
DOCTOR | DECEMBER ISSUE
 INFLUENZA
can be detrimental to
the ELDERLY1,2

Individuals aged ≥ 65 years who contracted influenza are at an

increased risk of complications and hospitalisation1,2

Over 30% of elderly patients hospitalised for acute illnesses

such as influenza had worse functional status after discharge3

Influenza vaccination confers multiple benefits to elderly individuals:4

46% Pneumonia
45% Hospital
47%All-cause
prevention admission mortality*

Immunogenic against 4 key influenza strains5

Well-tolerated with a good safety profile5
0.5 ml dosing for all individuals aged 6 months and above5
Suitable for use during pregnancy5
May be used during breastfeeding5

Vaccinate now to keep the elderly protected from influenza

Abbreviated prescribing information
1. TRADE NAME OF THE MEDICINAL PRODUCT AND PRESENTATION: VaxigripTetra, Quadrivalent influenza vaccine. Active Ingredient: Split influenza virus (inactivated) with qualitative and quantitative composition of the vaccine updated every
year according to the recommendations of WHO. Pharmacotherapeutic class: Influenza, inactivated split virus. Dosage forms and strengths: VaxigripTetra vaccine 0.5ml prefilled syringe. 2. THERAPEUTIC INDICATION: Vaccine against seasonal
influenza. 3. DOSAGE AND INSTRUCTIONS FOR USE: Adults and children from 6 months receive one 0.5ml dose. For children less than 9 years of age who have not been vaccinated previously, a second dose should be given after at least 4 weeks.
Regarding passive protection, one 0.5 ml dose administered to a pregnant woman may protect infants from birth to almost 6 months of age; however, not all infants may be protected. Immunisation should be carried out by intramuscular or
subcutaneous injection. 4. CONTRAINDICATIONS: Hypersensitivity to the active substances, to any of the excipients and to residues that may be present in very small amounts such as eggs (ovalbumin or chicken proteins), neomycin, formaldehyde
or octoxynol-9. Vaccination shall be postponed in individuals with febrile illness or acute infection. 5. SPECIAL WARNINGS AND PRECAUTIONS: Special precautions in individuals with poor immune responses. False positive blood test results have
been observed in patients who had recently been vaccinated. 6. PREGNANCY AND LACTATION: VaxigripTetra can be used in all stages of pregnancy. Larger datasets on safety are available for the second and third trimester, compared with the first
trimester; however, data from worldwide use of inactivated influenza vaccines, including Vaxigrip do not indicate any adverse foetal and maternal outcomes attributable to the vaccine. VaxigripTetra may be used during breastfeeding.
7. UNDESIRABLE EFFECTS: Most frequently reported side effect in all population was injection site pain. In children less than 24 months of age, irritability was most frequently reported. In children from 24-35 months of age, malaise is most
frequently reported. Other common reported adverse reactions include headache, myalgia, malaise, fever, shivering. Local reactions include redness, swelling pain, bruising (ecchymosis), hardness (induration) around the area where the vaccine is
injected. Reactions usually subside within 1 to 3 days without treatment. Other side effects reported are allergic reaction, anaphylaxis, skin reactions, blood vessel inflammation, neuralgia, neuritis, convulsions, Guillain-Barré syndrome and
inflammation of brain & spinal cord typically due to acute viral infection. 8. INTERACTIONS: VaxigripTetra can be given the same time with other vaccines on separate limbs in which case the side effects may be intensified. The immunological
response may decrease in case of immunosuppressant treatment, such as corticosteroids, cytotoxic drugs or radiotherapy. 9. OVERDOSE: No cases of overdose have been reported 10. Revision Date: July 2020. 11. Full prescribing information available
on request from Sanofi Pasteur, vaccines division of sanofi-aventis (Malaysia) Sdn. Bhd., Unit TB-18-1, Level18, Tower B, Plaza 33, No.1, Jalan Kemajuan, Seksyen 13, 46200 Petaling Jaya, Selangor Darul Ehsan, Malaysia. Ref No.
MY/VAXQ/V03/0120

References:
1. World Health Organization. Influenza (seasonal). Available at https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal). Accessed on 4 February 2020. 2. European Centre for Disease Prevention and Control.
Factsheet about seasonal influenza. Available at https://ecdc.europa.eu/en/seasonal-influenza/facts/factsheet. Accessed on 4 February 2020. 3. Boyd CM, Landefeld CS, Counsell SR, et al. Recovery of activities of daily living in older
adults after hospitalization for acute medical illness. J Am Geriatr Soc. 2008;56(12):2171-9. 4. Lang P. Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence. Clin Interv Aging. 2012:7:55–64.
5. VaxigripTetra full prescribing information. Date of revision: July 2020.

SANOFI PASTEUR c/o sanofi-aventis (Malaysia) Sdn. Bhd. (334110-P)

Unit TB-18-1, Level 18, Tower B, Plaza 33, No.1 Jalan Kemajuan, Seksyen 13, 46200 Petaling Jaya, Selangor Darul Ehsan, Malaysia.
Tel: +603-7651 0800 Fax: +603-7651 0801/0802

© 2020 Sanofi. All rights reserved. For healthcare professionals only. MAT-MY-2000481 – 1.0 – 09/2020
 MALAYSIA FOCUS

New biologic enters fight against psoriasis

PEARL TOH

A
new monoclonal antibody
which targets interleukin-23 (IL-
23) is now available in Malaysia.
Guselkumab (TREMFYA™, Janssen
Pharmaceutical Companies of John-
son & Johnson) is a subcutaneously
injected agent that blocks the body’s
inflammatory pathway, namely, IL-23.

“Factors affecting the

L-R: Sophia Lim, Head of Marketing; Dr. Peter Ch’ng, Dr. Ch’ng Chin Chwen, and Seri Naga
treatment regimen include
Leong, Senior Product Manager.
severity of disease, the
type of psoriasis, general Factors affecting the treatment regi- on guselkumab also achieved PASI
health status of patient, men include severity of disease, the 100 response, which is 100 percent
type of psoriasis, general health status clearance of psoriasis, at week 48.
and burden of disease to [Lancet 2019;394:831–839] Further
of patient, and burden of disease to
the patient.” the patient. Treatment options cover trials are ongoing for guselkumab in
general areas such as topical agents, patients with psoriatic arthritis and
phototherapy, and finally, systemic Crohn’s disease.
The new drug regimen involves agents.
two loading or starter doses—the first
at the beginning of treatment and one Common topical agents are coal “... 84 percent of
more at the 4-week mark. Thereafter, tar, corticosteroids, salicylic acid, cal-
the patient is given one injection ev- cipotriol, dithranol, and calcineurin in-
patients administered
ery 8 weeks. Guselkumab provides a hibitors. Systemic agents include the with guselkumab were
“consistent maintenance of efficacy” standard immunosuppressants such found to have achieved
to patients, said Chin Keat Chyuan, as methotrexate, retinoids and cyclo- at least 90 percent
managing director of Johnson & John- sporine; the newer small molecules,
son Malaysia. and most recently, the biologics.
improvement ...”

In line with their efforts to increase Also present at the launch, Dr

awareness about psoriasis treatment, Peter Ch’ng Wee Beng, a consultant VOYAGE 1** demonstrated the
Chin announced the launch of their dermatologist, spoke about the trials guselkumab’s long-term efficacy in
patient awareness programme called that provided the evidence base for which 82 percent of patients receiving
‘PsO Much More’ to put the word guselkumab, namely the ECLIPSE* treatment continuously achieved at
out about guselkumab’s efficacy in study, a randomized, double-blinded, least 90 percent improvement in the
patients afflicted by the disfiguring comparator-controlled trial that proved PASI 90 response at 4 years. Addi-
disease. Chin added: “Patients with the safety and efficacy of the drug in tionally, the study revealed guselkum-
psoriasis can certainly look forward to adult patients with moderate-to-se- ab was well tolerated in patients with
effectively manage their disease with vere plaque psoriasis. The study, in- psoriasis. [Available at: https://doi.or
lasting efficacy, regain their self-es- volving 1,048 patients, showed that g/10.1080/09546634.2020.1782817
teem and lead quality lives.” 84 percent of patients administered Accessed on 10 November]
with guselkumab were found to have
Speaking at the launch, Dr Ch’ng achieved at least 90 percent improve- * ECLIPSE: Guselkumab versus secukinumab for
Chin Chwen, a consultant derma- ment in their baseline Psoriasis Area the treatment of moderate-to-severe psoriasis
** VOYAGE 1: A study of guselkumab in the
tologist, said psoriasis requires per- Severity Index (PASI 90) score at week treatment of participants with moderate-to-
sonalized treatment for each patient. 48. Additionally, 58 percent of patients severe plaque-type psoriasis

14
DOCTOR | DECEMBER ISSUE
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COVER STORY

16
DOCTOR || DECEMBER ISSUE
 COVER STORY

ELVIRA MANZANO be much more expensive and difficult.” nCoV-19. [Lancet 2020;doi:10.1016/
To smooth ruffled feathers, Pfizer S0140-6736(20)32466-1] Some 50

G
reat news. At least one vaccine said the vaccine can last in a specialty other vaccine candidates are in early
– or two – could be approved in freezer for up to 6 months. A “cool box” stages of testing, including one being
record time, raising hopes that will transport the vaccine, with dry ice conducted in Singapore.
the end of the COVID-19 pandemic around it, to keep the right tempera-
may be in sight in early 2021. ture. “It has actually a device within it Third wave of pandemic
that has a continuous GPS and tem- threatens nations
Drug makers Pfizer and Moderna perature monitor,” said Tanya Alcorn, WHO Director-General Tedros Ghe-
have announced promising interim re- vice president, Pfizer’s BioPharma breyesus said the world is at a “critical
sults for their respective vaccine candi- Global Supply Chain. juncture” and the next few months will
dates. Pfizer, which developed its vac- be tough, with many countries seeing
cine with German partner BioNTech, The Moderna vaccine, on the other an exponential increase in cases. Eu-
has filed emergency use authorization hand, “can be distributed in a standard rope, for example, briefly enjoyed sink-
(EUA) – a temporary approval to accel- fashion – health workers are used to it, ing infection rates during summer, but
erate the availability of medical prod- facilities are used to it – it’s more nor- are now surging again. It is likely to see
ucts during a public health emergency mal,” explained Kristensen. a third wave of the pandemic before a
– for its COVID-19 vaccine, close on vaccine can be introduced, warned
the heels of reports that the vaccine “We don’t need [ultracold condi- WHO special COVID-19 envoy David
was 95 percent effective in preventing tions] as the quality of our product has Nabarro. In the US, cases climbed to-
COVID-19 in a large, phase III trial. improved and [it] doesn’t need to be ward a third peak, trending upward in
The study findings have yet to be pub- highly frozen to avoid mRNA degrada- most states, many of which are setting
lished or peer-reviewed though. tion,” added Moderna spokesperson new case records.
Colleen Hussey.
Joining Pfizer as a front-runner in Alarms were also sounded in Aus-
the race to contain the raging pan- “It is great news [that] there may be tralia, Japan, and South Korea, with
demic, the Moderna vaccine was 94.5 two vaccines that are effective … that COVID-19 cases peaking again.
percent effective at protecting against means we can reach more people,”
COVID-19 in an interim analysis of the said Ms Christine Finley, immunization To avert unnecessary deaths, pre-
COVE study. programme manager at Vermont’s vent essential health services from
Health Department in Burlington, Ver- collapsing, and schools from shutting
Should the US FDA approve the mont, US. “We need to show the vac- again, the WHO urged leaders to take
vaccines, distribution presents a cines are safe and effective. And we immediate action. Frontline healthcare
daunting challenge, according to vac- need to build public trust.” workers and essential workers, as well
cine experts. as nursing home residents, are among
The more vaccines the better the first to get vaccine jabs in the initial
The Pfizer COVID-19 vaccine With some modicum of excitement and rollout.
needs to be stored at ultracold tem- hopes brought about by the possibility
perature – at minus 70 degrees Cel- of an approval of the first COVID-19 Given the size of the global popu-
sius to be exact, colder than winter in vaccine before Christmas, infectious lation plus the fact that each vaccine
Antarctica. The same is true for the disease experts said vaccine develop- requires two jabs at three weeks apart,
Moderna vaccine which needs to be ment is not a race. They said the more universal coverage will take a long
kept at minus 20 degrees Celsius, the vaccines are approved, the better, way. The approval of the first vaccine
temperature typical of a regular freez- because of the sheer number of peo- is now moving to the fore – a feat that
er. ple needing protection against SARS- should be celebrated – but is only one
CoV-2. step in the COVID-19 journey.
Ms Debra Kristensen, a veteran of
vaccine innovation and supply chains Ten other vaccine makers are now There are qualms about using an
at PATH, an international non-profit into phase III trials, including studies EUA for a vaccine that will be given
firm focused on public health, said it is in Australia, Britain, China, India, and to millions of people globally, but such
feasible to distribute the vaccines, just Russia. AstraZeneca and Oxford Uni- a criticism has been muted with hun-
like how the Ebola vaccine was suc- versity recently published favourable dreds of thousands of fallen bodies
cessfully distributed in a few African phase II/III data for its chimpanzee ad- hardest hit by one of history’s worst
countries. “But it’s definitely going to enovirus-vectored vaccine, ChAdOx1 pandemics.

17
DOCTOR || DECEMBER ISSUE
 COVER STORY

SARS-CoV-2 antibodies months after contracting COVID-19. Of

these patients, 75 percent showed me-

detectable up to 6 months after dium to high antibody titres (>300 units).

COVID-19 onset Furthermore, the researchers found

that neuralization activity correlated with
IgG titre level.
PEARL TOH response over a period of 5 months

S
after symptom onset. [Eur J Immunol “Although we observed a reduction
ARS-CoV-2 antibodies remained 2020;doi:10.1002/eji.202048970] in the levels of antibodies over time, the
detectable up to 6 months after results of our neutralising assays have
infection in COVID-19 patients, “The results of this 6 months shown a robust neutralisation activity for
reveals a study. cross-sectional study show a classic up to the seventh month post-infection
pattern with a rapid increase of antibody in a large proportion of previously vi-
“[The study] highlights a continued levels within the first three weeks after rus-positive screened subjects,” report-
level of circulating neutralising antibodies COVID-19 symptoms and, as expect- ed Veldhoen.
in most people with confirmed SARS- ed, a reduction to intermediate levels
CoV-2,” the researchers stated. thereafter,” explained lead investigator “[This finding] suggests that most
Dr Marc Veldhoen from Instituto de Me- people infected with SARS-CoV-2 will
In addition, the results also suggest dicina Molecular João Lobo Antunes in have circulating protective immunity
that age was not a confounding factor Lisbon, Portugal. for many months after COVID-19,” he
for the antibody levels produced, but dis- added.
ease severity was. Around half of the sera samples col-
lected within the first week after symp- The researchers also saw differences
In the cross-sectional study, over 300 tom onset showed robust IgG serocon- in immune response between men and
hospitalized patients with COVID-19 and version, despite the fact that antibody women in the acute phase of infection.
healthcare workers, 198 post-COVID-19 responses usually take time to mature.
volunteers, and 2,500 university staff These participants who had early sero- “In the early response phase, on
were monitored on their humoral immune conversion continued to maintain high average men produce more antibodies
levels of IgG in the subsequent week. than women, but levels equilibrate during
the resolution phase and are similar
Notably, 90 percent of previously between the sexes in the months after
infected participants harboured detect- SARS-CoV-2 infection,” said Veldhoen.
able antibodies at 40 days and up to 6
When stratifying the analysis by age,
there were no significant differences be-
tween age groups — indicating that age
did not represent a confounding factor
for antibody production. However, anti-
body levels were higher in patients with
more severe disease in the acute phase.

“Our work provides detailed informa-

tion for the assays used, facilitating fur-
ther and longitudinal analysis of protec-
tive immunity to SARS-CoV-2,” Veldhoen
pointed out.

“The next months will be critical to

evaluate the robustness of the immune
response to SARS-CoV-2 infection, and
to find clues for some open questions,
such as the duration of circulating anti-
bodies and the impact of reinfection.”

18
DOCTOR || DECEMBER ISSUE
 COVER STORY

Frontline workers buckle under pressure

of COVID-19
TRISTAN MANALAC In multivariable logistic regression “To our knowledge, this is the first

A
analysis, the presence of physical symp- multicentre study that has examined the
mid the novel coronavirus disease toms, such as lethargy, headaches, and prevalence of psychological outcomes
(COVID-19) pandemic, healthcare throat pain, emerged as a significant in- among healthcare workers during the
workers in Asia are suffering from dicator of depression (odds ratio [OR], evolution of the COVID-19 pandemic in
high rates of psychological distress as 5.673, 95 percent confidence interval the Asia-Pacific region,” the researchers
shown in a recent study. The rates vary [CI], 1.780–18.075; p=0.003) and In- said.
greatly across countries and seem inde- donesian (OR, 1.241, 95 percent CI,
pendent of the case burden. 1.010–1.526; p=0.04) among Malaysian “Therefore, as the pandemic reach-
healthcare workers. es its peak, it calls for urgent clinical and
From 29 April to 4 June 2020, 1,146 policy strategies for identifying healthcare
healthcare workers across five Asia-Pa- In addition, nonmedically trained workers at risk, [such as] those who are
cific countries (India, Indonesia, Malaysia, frontline workers, such as administrative not medically trained, those with physical
Vietnam, and Singapore) were enrolled personnel, were significantly more likely symptoms and prior medical conditions,”
in the study. A self-administered survey to have anxiety in the Indonesian sub- they added.
showed that lethargy and headaches group (OR, 4.908, 95 percent CI, 1.282–
were common physical symptoms, man- 18.789; p=0.02). “Passive psychoeducation through
ifesting in 36.2 percent and 33.5 percent educational pamphlets, emails, or web-
of participants, respectively. [BJPsych Among Singapore healthcare work- site can be relatively easy and inexpen-
Open 2020;6:e116] ers, having had medical conditions in the sive to implement and may serve as a
past was tied to anxiety (OR, 5.828, 95 readily available resource for those ex-
During the study period, Singapore percent CI, 1.397–24.308; p=0.016) and periencing psychological distress,” the
logged the highest number of daily cases, COVID-19-related PTSD (OR, 2.425, researchers said.
confirming 109.6 infections per day per 1 95 percent CI, 1.014–5.802; p=0.046).
million population. This was followed by Other predictors of PTSD in frontline
Malaysia, Indonesia, and India (1.9, 1.8, workers were being nonmedically trained
and 1.2 cases per day per 1 million pop- (OR, 2.729, 95 percent CI, 1.150–6.472;
ulation). Vietnam, at 0.03 confirmed in- p=0.023) and having physical symp-
fections per day per 1 million population, toms (OR, 6.692, 95 percent CI, 1.517–
had the lowest case rate. 29.521; p=0.012).

Despite this trend in case bur-

den, healthcare workers from Viet-
nam showed the highest prevalence of
COVID-19-related post-traumatic stress
disorder (PTSD), as defined by the Im-
pact of Events Scale-Revised (IES-R),
at 15.0 percent. Overall, 91 patients (7.9
percent) had PTSD related to the pan-
demic.

The overall prevalence of depression

was 4.5 percent, and anxiety was report-
ed in 5.2 percent of participants. The
overall mean scores for the respective
subdomains in the Depression Anxiety
Stress Scales (DASS-21) were 1.89 and
1.95.

19
DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Association for the Study of Liver Diseases (AASLD 2020) - The Liver Meeting Digital Experience

AASLD 2020
November 13-16

November 13-16

HBV suppressed on long-term tenofovir

alafenamide; switch from TDF improves safety
JAIRIA DELA CRUZ First, kidney function got better, and >38 U/L in women, and eGFRCG was

T
as demonstrated by improvements in ≥50 mL/min.
enofovir alafenamide (TAF) keeps estimated glomerular filtration rate by
chronic hepatitis B virus (HBV) in Cockcroft-Gault (eGFRCG) and markers Over 5 years of treatment, TAF nor-
check through 5 years of treat- of proximal tubular function. Second, malized ALT, and the rates were similar in
ment, with an added benefit of improving the early declines in bone mineral den- the three treatment groups (2018 AASLD
bone and kidney safety outcomes in pa- sity (BMD) seen during TDF treatment Criteria, 74–76 percent; Central Labora-
tients who have switched from tenofovir steadily increased after the switch, which tory, 84–88 percent). The same was true
disoproxil fumarate (TDF), according to according to Chan provided evidence for rates of HBeAg loss (37–39 percent)
data from two ongoing phase III studies. that TDF-induced bone loss could be and seroconversion (21–27 percent),
reversed. which remained low throughout. Fibrosis
remained stable, if not improved.
“TAF will be a better The analysis was based on the 5-year
results of two identically designed phase Chan and colleagues found no geno-
alternative to patients III studies: study 108, which comprised typic resistance to TAF at year 5 among
who may require TDF 425 HBeAg-negative patients, and study the 44 patients who qualified for se-
treatment, and TAF can 110, which involved 873 HBeAg-positive quencing. Eight patients with amino acid
be a first-line treatment patients. Initially, these patients had been changes from baseline are undergoing
randomized to take TAF 25 mg or TDF phenotypic testing with results pending.
for viral hepatitis B” 300 mg once daily for 2 or 3 years, fol-
lowed by open-label (OL) TAF until year
5. “The longer-term safety
More than 90 percent of patients
and efficacy data can
maintained virologic control (HBV DNA In total, 1,157 patients (89 percent)
<29 IU/mL) overall, with the rates not sig- entered the OL phase, but only 999 pa- provide confidence
nificantly different between patients who tients (77 percent) remained on treat- to clinicians to use
used TAF throughout and those initially ment at year 5, including 675 who stayed TAF as a long-term
treated with TDF but switched to TAF at on TAF and 136 and 288 who switched
therapy for their chronic
year 2 or 3 (93–96 percent), said pre- from TDF and started TAF at year 2
senting author Dr Henry Chan from The (TDF–TAF OL 3y) or at year 3 (TDF—TAF hepatitis B patients”
Chinese University of Hong Kong during OL 2y), respectively.
AASLD 2020.
The majority of the population were Among the treatment groups, grade
Long-term TAF treatment was safe men, Asian, and HBeAg-positive. Nearly 3/4 adverse events (AEs; 3–7 percent)
and well tolerated. Chan highlighted im- half had HBV genotype C. At baseline, and AEs leading to discontinuation (0–1
portant changes that occurred following mean HBV DNA at baseline was ≥7.0 percent) were infrequent. The chang-
the switch from TDF to TAF. log10 IU/mL, ALT was >60 U/L in men es in fasting lipids with TAF or following

20
DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Association for the Study of Liver Diseases (AASLD 2020) - The Liver Meeting Digital Experience
November 13-16

TDF-to-TAF switch were not likely to “TAF will be a better alternative to 1906; Antimicrob Agents Chemoth-
have any clinical impact for most pa- patients who may require TDF treatment, er 2015;59:3563-3569; J Hepatol
tients, Chan said. and TAF can be a first-line treatment for 2015;62:533-540]
viral hepatitis B,” he added.
Meanwhile, the eGFRCG decline was
minimal throughout, and hip and spine TAF is a novel tenofovir (TFV) prod-
BMD remained stable in the TAF group. rug, which has greater plasma stability
than TDF. It touts enhanced delivery of
“The longer-term safety and efficacy active drug (TFV-diphosphate) to he-
data can provide confidence to clinicians patocytes, with reduced circulat-
to use TAF as a long-term therapy for ing TFV levels relative to TDF.
their chronic hepatitis B patients,” Chan [Mol Pharm 2013;10:459-
said when contacted for comments by 466; Antimicrob Agents
MIMS Doctor. Chemother 2005;49:1898-

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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Association for the Study of Liver Diseases (AASLD 2020) - The Liver Meeting Digital Experience
November 13-16

Low liver fat

may be bad
for the heart

STEPHEN PADILLA divided participants into four phenotype p=0.495). [AASLD 2020, abstract 89]

T
groups defined by sex-specific median
he distribution of body fat contrib- values of VAT and LF: low VAT-low LF, After adjusting for confounding fac-
utes to the risk of coronary heart low VAT-high LF, high VAT-low AF, and tors, the strong association between
disease (CHD), with the risk of high VAT-high LF. high VAT-low LF and increased CHD
cardiovascular events further increasing risk persisted (adjusted OR, 1.65, 95
among individuals with low liver fat (LF) The associations of VAT-LF groups percent CI, 1.03–2.63), but the link be-
and high visceral adipose tissue (VAT) or with incident CHD (ischaemic heart dis- tween high VAT-high LF and CHD was
abdominal fat, results of a recent study ease or presence of aortocoronary by- reduced (adjusted OR, 1.00, 95 percent
have shown. pass graft) were assessed using logistic CI, 0.64–1.58; p=0.983).
regression analysis. The researchers
Such finding indicates that liver tri- also calculated odds ratios (ORs) and “These results indicate the impor-
glyceride regulation has a significant im- 95 percent confidence intervals (CIs) tance of proper liver triglyceride regula-
pact on cardiovascular health in individ- with low VAT-low LF as reference, with tion in the context of visceral adiposity,”
uals with frictional VAT and LF. an additional analysis adjusting for age Linge said, noting that a decrease in liver
and body mass index (BMI). fat alone might be insufficient to reduce
“Recent studies have shown differ- the cardiometabolic risk of patients with
ent fat deposits have variable impact Participants (mean age 62.6 years, nonalcoholic fatty liver disease.
on the development of cardiometabol- 51 percent female, BMI 26.6 kg/m2)
ic disease, said co-author Ms Jennifer were followed for a mean of 1.3 years, “In fact, it seems that a decrease in
Linge, lead scientist at AMRA Medical with a total of 176 CHD events recorded liver fat without a resolution of visceral
AB in Linköping, Sweden, who present- following imaging. Sex-specific median obesity may put the patient at a great-
ed the study at AASLD 2020. values for females and males were 2.3 er risk of developing heart disease. This
and 4.7 L for VAT and 2.2 percent and is what we want to investigate further,”
“Understanding patients’ individual 3.1 percent for LF, respectively. she added.
way of storing fat can be valuable in de-
veloping targeted prevention and treat- The combination of high VAT and Further research is warranted to
ment strategies,” she added. low LF showed the most robust asso- determine if a discordant VAT-LF phe-
ciation with an increased risk of incident notype is an expression of an inability
Linge and her team used magnet- CHD (OR, 2.33, 95 percent CI, 1.50– to handle ectopic fat deposition via the
ic resonance images scanned from 3.58; p<0.001). On the other hand, the liver associated with incident CHD, and
12,276 individuals in the UK Biobank combination of low VAT and high LF if decreased LF due to liver dysfunction
imaging study to measure VAT and liver did not correlate with higher CHD risk heightens CHD risk, according to the
proton density fat fraction. Then, they (OR, 0.81, 95 percent CI, 0.42–1.45; researchers.

20
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Association for the Study of Liver Diseases (AASLD 2020) - The Liver Meeting Digital Experience
November 13-16

Slight amino
acid tweak
weakens HBV

TRISTAN MANALAC normalized levels of ALT relative to their In terms of viral dynamics, both

T
wildtype counterparts (67.5 percent vs HBsAg (–0.25 vs –0.12 log IU/mL/year;
he substitution of isoleucine to leu- 40.0 percent; p=0.016). This was ac- p=0.029) and HBV DNA (–0.36 vs –0.12
cine at amino acid 97 (I97L) in the companied by a generally lower ALT level log copies/mL/year; p=0.030) levels
core region of the hepatitis B virus that was of borderline significance (23.1 dropped at a significantly faster rate in
(HBV) seems to reduce its potency, de- vs 30.1 IU/L; p=0.052). [AASLD 2020, I97L patients compared with their wild-
creasing the efficiency of both infection abstract 832] type counterparts.
and the synthesis of the virus’ covalently
closed circular (ccc) DNA, reports ex- Notably, HBsAg levels were also “Patients with chronic HB develop
perts at AASLD 2020. significantly suppressed in patients with liver cirrhosis and hepatocellular carci-
the I97L infection (1.3 vs 2.4 log IU/mL; noma along with the progress of hep-
Serum samples were collected from p=0.029), as were HBV DNA (2.4 vs 4.0 atitis. However, some of these patients
77 patients with chronic hepatitis B, who log copies/mL; p<0.0001). naturally stabilize without treatment and
were infected with HBV genotype C. The eventually achieve a favourable status
researchers excluded patients who also with low HBV DNA and normal ALT. In
had liver cirrhosis, as well as those who some cases, these patients also exhib-
“This I97L-associated
had undergone treatment with nucle- it loss of HBsAg,” the researchers said,
os(t)ide analogues and interferons. Only
low efficiency of noting that the exact mechanisms for this
those negative for the HB envelope anti- cccDNA synthesis remain unexplained.
gen and positive for its cognate antibody seems to be involved
were included. Through cell experiments, the re-
in the establishment of
searchers showed that the more favour-
Forty participants under investigation
stable hepatitis” able HB marker profile in I97L patients
carried the I97L polymorphism, while 37 was due to “the generation of immature
had the wildtype HBV. Both groups were virions with single-stranded genomes,”
comparable in terms of baseline demo- As a result, significantly more pa- which led to a weaker viral infection and
graphics, alanine aminotransferase (ALT) tients carrying the I97L HBV virus had cccDNA synthesis.
levels, platelet counts, and HBV DNA undetectable sAg levels relative to those
and HB surface antigen (HBsAg) con- with the wildtype infection (27.5 percent “This I97L-associated low efficien-
centrations. vs 8.1 percent; p=0.028). The same was cy of cccDNA synthesis seems to be
true when HBV DNA was used as mea- involved in the establishment of stable
Over an average observation period surement (35.0 percent vs 10.8 percent; hepatitis,” they explained. “Further study
of 7.2 years, significantly more patients p=0.012). on this mutation would be the hint for the
with the test polymorphism achieved FC mechanism.”

21
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Association for the Study of Liver Diseases (AASLD 2020) - The Liver Meeting Digital Experience
November 13-16

Novel fatty acid synthase inhibitor for

NASH makes good in early trial
JAIRIA DELA CRUZ

T
he small molecule fatty acid syn-
thase (FASN) inhibitor TVB-2640
scores a win in addressing the
three key drivers of nonalcoholic steato-
hepatitis (NASH)—namely liver fat, fibro-
sis, and inflammation—in the phase II
FASCINATE-1 trial presented at AASLD
2020.

“TVB-2640 is an orally bioavailable,

first-in-class FASN inhibitor. FASN is a
key enzyme in the de novo lipogenesis
(DNL) pathway that is responsible for the
synthesis of excess fat and activation of
fibrogenic and inflammatory mechanisms
in the liver of patients with NASH,” said
presenting author Dr Rohit Loomba from TVB‐2640 demonstrated a clear noted parallel improvements in serum
the University of California San Diego in dose‐dependent effect on liver fat. markers of fibrosis and inflammation. For
San Diego, California, US. Week-12 data showed a mean reduc- example, in the 50-mg group, TIMP1 de-
tion of 9.6 percent in the 25-mg group creased by 18 percent (26-ng/mL reduc-
“The potent liver fat reduction, mea- (n=30; p=0.053) and of 28.2 percent in tion; p<0.05 vs placebo) while adiponec-
sured by an advanced magnetic res- the 50-mg group (n=28; p=0.001) as op- tin increased by 24 percent (vs 8 percent
onance imaging (MRI) method called posed to a 4.5-percent increase in the with placebo).
MRI-derived proton density fat fraction placebo group (n=27). [AASLD 2020,
(PDFF), combined with the additional bio- abstract 67] “A novel marker of DNL, serum tripal-
markers, demonstrates that TVB-2640 is mitin, was reduced in TVB‐2640-treat-
positively impacting multiple pathological A PDFF response occurred in the ed patients compared with placebo,
mechanisms causing liver damage in majority of patients in the 50-mg group confirming inhibition of FASN,” Loomba
NASH patients,” Loomba continued. (61 percent vs 11 percent with placebo; added.
p=0.001) and in 23 percent of the 25-mg
He pointed out that MRI-PDFF re- group. The drug was well tolerated, with
sponse was an accurate and reliable most adverse events (AEs) being mild in
biomarker, which was indicative of histo- Patients who received TVB‐2640 also severity. None of the patients developed
logical response and had been shown to exhibited declines in alanine aminotrans- serious AEs. Treatment did not signifi-
predict NASH resolution. ferase (ALT) levels, with a 20.4-percent cantly alter plasma triglycerides, and nei-
reduction in the 50-mg group (p=0.001) ther did it induce biochemical or haema-
FASCINATE-1 randomized 99 pa- and an even larger decrease in the tologic toxicity.
tients to receive placebo or TVB‐2640 subgroup of patients with baseline ALT
at 25 or 50 mg once daily for 12 weeks. greater than the upper limit of normal. “The treatment response seen in
Most patients had type 2 diabetes, and TVB-2640-treated subjects in this study,
the mean liver fat content at baseline There was also a marked drop in along with the additional biomarkers, in-
according to PDFF was 16.7 percent. low-density lipoprotein (LDL) cholesterol creases our confidence to embark upon
All patients had evidence of liver fibrosis with the 50-mg regimen vs placebo. a larger phase II liver biopsy-based clini-
(magnetic resonance elastography [MRE] cal trial in NASH patients with stage 2–3
≥2.5 kPa or liver biopsy F1‐F3). Moreover, Loomba and his team fibrosis,” concluded Loomba.

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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Association for the Study of Liver Diseases (AASLD 2020) - The Liver Meeting Digital Experience
November 13-16

TAF during pregnancy curbs HBV

transmission from mother to child
PEARL TOH lin and HBV vaccination at birth, followed “There were no safety concerns for

A
by another two doses of vaccine at 1 and both mothers and infants with 28 weeks
ntiviral treatment with tenofo- 6 months each. [AASLD 2020, abstract of follow-ups,” the researchers reported.
vir alafenamide fumarate (TAF) 0020] Approximately 15 percent of pregnant
during pregnancy in highly virae- mothers experienced postpartum ALT
mic mothers effectively prevents mother- At delivery, HBV suppression was flares (mean ALT peak level of 140.2
to-child transmission (MTCT) of hepatitis observed in 85.9 percent of mothers, U/mL). There were no severe adverse
B virus (HBV) with no safety concerns, who had successfully achieved serum events (AEs) in both mothers and infants.
according to two studies presented HBV DNA levels <200,000 IU/mL (mean
during the AASLD 2020 Liver Meeting. HBV DNA levels, 4.09 log10 IU/mL), with Similar findings
a mean reduction of 3.69 log10 IU/mL in in separate study
While other antiviral agents have maternal serum HBV DNA from baseline. The safety and efficacy of TAF during
been shown to prevent perinatal MTCT pregnancy was further supported in an-
of HBV from highly viraemic mothers, At 24-28 weeks since birth, none of other multicentre, prospective study with
data on TAF is still lacking, the research- the infants who completed immunopro- similar design, enrolling 116 mothers.
ers pointed out. phylaxis regimens had hepatitis B s-an- [AASLD 2020, abstract 0160]
tigen and their HBV DNA levels were un-
detectable (<100 IU/mL) — showing that HBV DNA levels were suppressed to
“There were no safety TAF effectively prevented MTCT of HBV. <200,000 IU/mL in all mothers at deliv-
concerns for both ery, with none having HBeAg or HBsAg
Growth measures of infants such as loss. Importantly, none of the 117 infants
mothers and infants with height, weight, and head circumferences were positive for HBsAg at 7 months,
28 weeks of follow-ups” also matched the physical development including 46 (39.3 percent) infants who
requirement set out in national standards. were breastfed.

In a multicentre, single-arm, retro- No congenital defects or malforma- Again, TAF was well tolerated with no
spective cohort study, 71 hepatitis B tion were reported at birth among the treatment discontinuation due to AEs.
e-antigen (HBeAg)-positive mothers infants.
(mean age 30.3 years) with HBV DNA Nausea was the most common AE,
>200,000 IU/mL were treated with TAF In addition, breastfeeding did not in- occurring in 19 percent of the partici-
therapy in the third trimester of pregnan- crease the risk of HBV infection among pants. Premature rupture of membranes
cy. All infants (n=73) received immuno- the 66 percent of infants who were (12.9 percent) constitute the most fre-
prophylaxis of hepatitis B immunoglobu- breastfed. quent complication, while anaemia (30.2
percent) was the most common labo-
ratory abnormality. Elevated ALT levels
were seen in one, three, and nine moth-
ers at delivery, 3 and 6 months postpar-
tum, respectively.

There were no birth defects among

the infants. Similarly, physical and neuro-
logical development of the infants were
comparable with national standards at
birth and 7 months.

*ALT: Alanine aminotransferase

23
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DOCTOR || DECEMBER ISSUE
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 Sponsored Symposium Highlights

Combating the COVID-19

Crisis: Today and Beyond
At a Pfizer-sponsored webinar held in collaboration with the Malaysian Medical
Association, several distinguished speakers shared their insights into the current SARS-
COV-2 pandemic, better known as COVID-19. Topics discussed include current and
future therapeutic interventions from both local and global perspectives.
Faculty: Faculty:
Dr Yasmin Mohamed Gani Dr Suresh Kumar Chidambaram
Chairperson: Consultant Infectious Disease Physician, Consultant Infectious Diseases Physician
Datuk Dr Christopher Lee Kwok Choong Hospital Sungai Buloh, Malaysia Hospital Sungai Buloh, Malaysia
Head of National COVID-19 Mortality
Review Committee; Selangor Faculty: Faculty:
COVID-19 Taskforce Member Prof Matteo Bassetti Dr Amgad Gamil
Head of the Infectious Diseases Division Santa Senior Director, Emerging Markets
Maria Misericordia University Regional Medical Lead, Africa,
Hospital, Udine, Italy Middle East & Asia regions, Pfizer

Tackling the COVID-19 pandemic Transmission of COVID-19 occurs primarily via respiratory
As of July 2020, the COVID-19 pandemic has spread to droplets (ie, cough, sneezing, talking) and to a lesser extent,
almost every country around the world, accounting for over contact with contaminated surfaces. As the SARS-COV-2
12 million cases and 550,000 deaths.1 In Malaysia, there have virus is highly contagious, the risk of infection increases
been over 8,000 clinically confirmed cases of COVID-19 with proximity and length of interaction.6 Based on an
with 125 mortalities.2 While individuals of all ages are at risk epidemiological study, the likelihood of transmission is highest
of infection, the risk for serious disease is greater among during the first 5 days of illness and subsequently reduces
individuals aged over 60 years with multiple comorbidities after day 7 of symptom onset.7 Of note, viral RNA may be
and those living in confined spaces (eg, nursing homes).3 detected in upper respiratory specimens from asymptomatic
or presymptomatic patients with COVID-19; however,
evidence on the extent of asymptomatic transmission
Symptoms and transmission remains inconclusive.1 Thus, prevention is currently focused
Symptoms of COVID-19 often appear after a median of on social distancing measures, the use of face masks and
5–6 days and may vary based on the patient’s current good hygiene practices (eg, frequent handwashing).6
stage of disease (Figure 1).1,4 The initial infection stage
occurs following first exposure and inoculation of disease,
during which viral replication rate is the highest (ie, viral Screening for SARS-COV-2 infection
response phase).1,4 At this stage, patients often present As COVID-19 often manifests as pneumonia,
with nonspecific symptoms such as fever and dry cough4; radiological imaging (eg, chest x-ray, computed
however, some patients may experience new loss of tomography) plays a vital role in the diagnostic
taste and/or smell.5 As the disease progresses, localised process. 5 Common laboratory findings associated with
inflammation in the lung leads to viral pneumonia and the infection include lymphopaenia and elevated
hypoxia (ie, pulmonary phase), and patients often require levels of aminotransferase, C-reactive proteins (CRP),
hospitalisation for worsening respiratory failure. If patients D-dimer, ferritin and lactate dehydrogenase. 1 Results
progress to severe COVID-19, the disease manifests from diagnostic tests should be interpreted based on
as acute respiratory distress syndrome (ARDS) marked the accuracy of each test and the pretest probability
by systemic hyperinflammation (ie, host inflammatory (ie, estimated risk of disease). 8 Importantly, a single
response phase).5 negative test should not be used to rule out patients
with strongly suggestive symptoms. 8 One study found
that only 63% of nasal swab samples – collected from
Figure 1. The clinical stages of COVID-194 patients diagnosed with COVID-19 – returned positive
results (ie, 37% false negatives). 9 This has infection
Stage I Stage II Stage III
(Early infection) (Pulmonary phase) (Hyperinflammation phase) control implications as inaccurate diagnostic tests
IIA IIB may undermine pandemic control measures; false
Severity of illness

negative results allow infected individuals to transmit

Viral response phase the disease further into the community. 10
Host inflammatory response phase According to Malaysian guidelines on COVID-19, any
individual presenting with acute respiratory symptoms
and either (i) a history of international travel within 2 weeks
Time course
Mild constitutional
of symptom onset, or (ii) close contact with a confirmed
Clinical
symptoms
Fever >99.6°F
Shortness of breath
Hypoxia
ARDS
SIRS/Shock
or suspected COVID-19 case, is considered a patient
symptoms
Dry cough, diarrhoea,
headache
(Pa02/Fi02 ≤300 mmHg) Cardiac failure
under investigation (PUI) and should be screened for
Lymphopenia, increased Elevated inflammatory
SARS-COV-2 infection.11 At present, there are three
Clinical
signs
prothrombin time,
increased D-dimer and
Abnormal chest imaging
Transaminitis
markers (CRP, LDH, IL-6,
D-dimer, ferritin) troponin,
diagnostic tests for COVID-19: reverse transcription
Low-normal procalcitonin
LDH (mild) NT-proBNP elevation
polymerase chain reaction (RT-PCR), rapid antigen test
kits and rapid antibody test kits (Table 1)12; of these, RT-PCR
Image adapted from Siddiqi HK, Mehra MR. J Heart Lung Transplant 2020;39:405–407. is considered the gold standard for diagnosis.13
 Sponsored Symposium Highlights

Table 1. Diagnostic tests for COVID-1912 antiviral therapy (interferon [IFN] β-1b, lopinavir/ritonavir
RT-PCR RTK Antigen RTK Antibody
and ribavirin) significantly reduced the median time to
negative nasopharyngeal swab (7 vs 12 days; p=0.001)
Diagnostic Detects SARS- Detects SARS- Detects host compared with lopinavir/ritonavir alone in patients
method COV-2 RNA COV-2 antigens antibodies
in respiratory within the host against SARS- hospitalised for COVID-19; however, IFN β-1b should not
samples1 COV-2 be prescribed after day 7 of symptom onset owing to
Sampling Nasopharyngeal Nasopharyngeal Blood test its proinflammatory effects.17 Separately, an open-label
swab swab study found that famipiravir reduced viral clearance time
(4 vs 11 days) and improved day-14 CT scans (91.43% vs
Diagnostic Sample is positive A positive test A positive test
value if the specified Ct is indicative of indicates prior
62.22%), with fewer reported adverse events compared
value is reached14 infection13 infection with lopinavir/ritonavir.18

Advantages High specificity High sensitivity, Identifies Several in vitro studies have reported that remdesivir and
removes the rapid turnover infection chloroquine may have potential antiviral activity against
need for lower and larger testing even among SARS-COV-2.19 Preliminary results from an randomised
respiratory capacity13; asymptomatic
tract samples May be used to individuals15
controlled trial (RCT) found that remdesivir shortened
to diagnose rapidly diagnose recovery time (11 vs 15 days), improved recovery rates
infection1; infected (rate ratio, 1.32; 95% CI, 1.12–1.55) and reduced mortality
Accurately individuals in (hazard ratio [HR], 0.70; 95% confidence interval [CI],
identifies infected early disease15 0.47–1.04) compared with placebo.20 Hydroxychloroquine,
individuals to stop
an analogue of chloroquine with fewer drug interactions,
further spread14
Disadvantages Does not indicate Risk of false A negative
is postulated to have an immunomodulatory effect that
current stage of positives; should test does not may help control the cytokine storm in late-stage SARS-
disease14 be interpreted rule out current COV-2 infection.21 However, a comparative observational
alongside RT-PCR infection; study found no benefits with hydroxychloroquine on ICU
results13 The presence admission rates, all-cause mortality or ARDS compared
of antibodies
do not indicate
with standard care; notably, the use of hydroxychloroquine
immunity15 was associated with cardiovascular side effects (SEs) that
necessitated treatment discontinuation.22 Moreover, data
RT-PCR, reverse transcription polymerase chain reaction; RTK, rapid test kit; SARS-
COV-2, severe acute respiratory syndrome coronavirus 2; Ct, cycle threshold from the RECOVERY trial found that hydroxychloroquine
did not improve mortality (HR, 1.11; 95% CI, 0.98–1.26) or
Pending laboratory results, all PUIs should undergo home duration of hospitalisation compared with standard care.23
surveillance or isolation at designated quarantine centres
for 14 days.11 If infection with SARS-COV-2 is confirmed, Inflammatory markers (eg, interleukin [IL]-6, CRP, D-dimers
patients must be admitted into a designated treatment and ferritin) are highly predictive of respiratory failure
hospital and triaged to ascertain their current stage of in patients with COVID-19; it has been reported that
disease (Table 2).16 patients with elevated levels of IL-6 and CRP (>80 pg/mL
and 97 mg/L, respectively) were more likely to require
Table 2. Clinical staging of COVID-1916 mechanical ventilation compared with patients with lower
levels of both markers.24 In an open-label pilot prospective,
Severity Category Characteristics
multicentre study, tocilizumab (a recombinant humanised
Mild 1 Asymptomatic Wide viral response phase, IL-6 monoclonal antibody) improved laboratory markers
tapers off after day 7 of illness
2 Symptomatic,
and survival rates (HR, 2.2; 95% CI, 1.3–6.7) in patients
no pneumonia hospitalised for severe COVID-19.25 Separately, one study
found that tocilizumab improved clinical outcomes and
3 Symptomatic,
pneumonia mortality in patients with severe COVID-19. All patients
who received tocilizumab were discharged after initiating
Severe* 4 Symptomatic, Cytokine release syndrome (CRS)
pneumonia requiring Characterised by prominent
the agent for an average of 15.1 days.26
supplemental oxygen host inflammatory response
Warning signs: Persistent Corticosteroids may benefit COVID-19 patients with
or new-onset fever and cytokine-related lung injuries owing to their potent anti-
increasing oxygen demands inflammatory effects.1 An observational study in China found
with increased CRP, increased that methylprednisolone reduced the risk of mortality
ferritin and persistently low
ALC levels <1.0, high IL-6 levels (HR, 0.38; 95% CI, 0.20–0.72) in COVID-19 patients with ARDS.27
Separately, the RECOVERY trial found that dexamethasone
Comorbid group
COVID-19 infection triggers improved mortality in COVID-19 patients who required
worsening of comorbid either mechanical ventilation (risk ratio [RR], 0.65; 95%
5 Critically ill with conditions (eg, ESRF, poor CI, 0.51–0.82) or supplemental oxygen (RR, 0.80; 95%
multiorgan cardiac function) CI, 0.70–0.92); however, patients with mild disease did not
involvement
Viral pneumonia group benefit from dexamethasone (RR, 1.22; 95% CI, 0.93–1.61).28
Mostly among elderly patients Based on available evidence, corticosteroids should only be
Prolonged viral response used in critically ill patients with ARDS or worsening respiratory
phase without CRS-associated
warning signs
failure in the absence of bacterial/fungal superinfections.29

*progression from mild to severe disease usually occurs between day 5–10 of illness
and is predictable based on clinical warning signs16
The need for anticoagulation
Patients with COVID-19 are at an increased risk of
ESRF, end-stage renal failure; CRP, C-reactive protein; IL, interleukin; ALC, absolute
lymphocyte count
venous thromboembolism (VTE) owing to coagulation
abnormalities (eg, increased fibrinogen, D-dimers), which
suggest a hypercoagulable state.30 Current guidelines
Potential therapeutic options in COVID-19 recommend the use of prophylactic anticoagulation,
Antivirals may be used to manage the early stages of unless contraindicated, in all patients hospitalised for
COVID-19 – a period when the viral replication rate of COVID-19. Of note, up to one-third of patients admitted
SARS-COV-2 is highest.1 One study found that combination to the ICU for COVID-19 will experience VTE (including
 Sponsored Symposium Highlights

deep vein thrombosis and pulmonary embolism [PE]), Additionally, secondary bacterial infections (SBI) may
despite the use of prophylactic anticoagulation30; these occur during later stages of COVID-19.29 The prevalence
patients may require intermediate-dose anticoagulation of SBI ranges 1–10% among patients with COVID-19,29 and
(ie, enoxaparin 0.5 mg/kg 12 hourly) even though data it is likely a key contributor to mortality; one study found
on such practice remain scarce.16 Patients with confirmed that SBI was present in 50% of mortalities associated with
VTE, suspected PE or clotting of vascular devices should COVID-19.32 Thus, empiric antibiotic treatment may be
receive full-dose anticoagulation (ie, enoxaparin 1 mg/kg considered in critically ill patients with pneumonia due to
12 hourly).30 COVID-19 (based on clinical syndrome, as well as local
guidelines and antibiotic susceptibility patterns) in whom
Current Malaysian guidelines to manage bacterial infection cannot be excluded.29

COVID-19 The Pfizer Five-Point Plan33

At present, the management of COVID-19 is focused on
general supportive care and symptomatic treatment.11  Sharing tools and insight with the scientific community
Specific pharmacological interventions recommended by using an open-source platform to rapidly advance
the current Malaysian Ministry of Health (MOH) guidelines† potential COVID-19 therapies.
are summarised below (Table 3).16  Marshalling our people of leading experts to accelerate
the discovery and development process.
 Applying our drug development expertise to support
Table 3. Current MOH guidelines on managing COVID-1916 any promising therapies from smaller biotech companies.
Drug Class Recommendation  Offering our manufacturing capabilities to support the
rapid distribution of life-saving breakthroughs to all
Anti-inflammatory IV dexamethasone 4 mg BD or TDS (3–5 days)
IV methylprednisolone 1–2 mg/kg OD (3–5
patients with COVID-19.
days)  Improving future rapid response using a collaborative
IV tocilizumab 4–8 mg/kg as a single dose – framework with federal agencies (including the NIH,
preferred in late presentation NIAID and CDC) when future epidemics surface.
Antivirals Lopinavir/ritonavir 2 tabs BD, or
Atazanavir 300 mg OD & ritonavir 100 mg OD, Key takeaways
and favipravir (Day 1: 1600 mg BD, then 600  Patients with COVID-19 often present with mild
mg BD)
disease, characterised by nonspecific symptoms
If <7 days of illness:
SC IFN β 1a 44 mcg STAT then EOD, or (eg, fever, malaise, dry cough)4 or experience new
SC IFN β 1b 250 mcg STAT then EOD loss of taste and/or smell, as well as diarrhoea.4,5
(3–5 doses) if evidence of CRS is present  Transmission of SARS-COV-2 occurs primarily via
respiratory droplets and can be prevented by social
Anticoagulation SC enoxaparin 0.5 mg/kg 12 hourly
distancing measures, face masks and good hygiene
Other interventions Monitoring warning signs in patients with severe practices.6
COVID-19 and pneumonia  RT-PCR is currently considered the gold standard for
Self-proning and CRIB diagnosing COVID-19.13
Monitoring drug-drug interactions
 All individuals that fulfil the criteria for PUI should be
IV, intravenous; BD, twice daily; TDS, three times daily; OD, once daily; screened for COVID-19 and quarantined for further
SC, subcutaneous; STAT, immediately; EOD, every other day; CRIB, complete rest management.11
in bed; IFN, interferon
 Immunomodulatory agents, antivirals and anticoagulants
†
The information presented in this article is updated as of 01/08/2020
may be used to manage patients with COVID-19.16
 The use of empiric antibiotic treatment may be
Challenges in managing COVID-19 patients considered in critically ill patients with pneumonia
Emerging data suggest that COVID-19 is associated due to COVID-19, in whom SBI cannot be excluded.29
with cardiac, dermatologic, haematological, hepatic,  The Pfizer Five-Point Plan outlines a collaborative
neurological, renal and other complications.1 One case framework designed to tackle the ongoing
series reported that COVID-19 was associated with multiple COVID-19 pandemic.33
complications, including ARDS (36.6%), continuous renal SARS-COV-2, severe acute respiratory syndrome coronavirus 2; COVID-19,
replacement therapy (2.8%), septic shock (4.7%), and the coronavirus disease 2019; RECOVERY, Randomised Evaluation of COVid-19
thERapY
need for mechanical ventilation (18.9%).31
References: 1. National Institutes of Health. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Available at: https://www.covid19treatmentguidelines.
nih.gov/. Accessed 28 July 2020. 2. Situasi Terkini. Available at: http://covid-19.moh.gov.my/terkini. Accessed 3 August 2020.3. World Health Organisation. Media
Statement: Knowing the risks for COVID-19. Available at: https://www.who.int/indonesia/news/detail/08-03-2020-knowing-the-risk-for-covid-19. Accessed 22 July
2020. 4. Siddiqi HK, Mehra MR. J Heart Lung Transplant 2020;39:405–407. 5. Cascella M, et al. Features, Evaluation and Treatment Coronavirus (COVID-19), StatPearls
Publishing, 2020. 6. Centres for Disease Control and Transmission. How COVID-19 Spreads. Available at: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-
sick/how-covid-spreads.html. Accessed July 22, 2020. 7. Cheng HY et al. JAMA Intern Med 2020: e202020. 8. Watson J et al. BMJ 2020;369:m1808. 9. Wang W, et
al. JAMA 2020;323:1843–1844. 10. Woloshin S, et al. N Engl J Med 2020. doi: 10.1056/NEJMp2015897. 11. Kementerian Kesihatan Malaysia. Guidelines on COVID-19
Management in Malaysia. 5th Ed, 2020. 12. Kementerian Kesihatan Malaysia. InfoSihat COVID-19: RT-PCR vs RTK Antigen vs RTK Antibodi. Available at:https://www.
infosihat.gov.my/images/media_sihat/infografik/jpeg/RT-PCR vs Rapid Test-01.jpg. Accessed 21 July 2020. 13. Gani Y. Diagnosing COVID-19. Presented at: Combating
the COVID-19 Crisis: Today and Beyond; 20 June 2020; KL, Malaysia. 14. Tom MR, Mina MJ. Clin Infect Dis 2020:ciaa619. 15. Centres for Disease Control and Transmission.
Interim Guidelines for COVID-19 Antibody Testing. Available at: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html. Accessed
22 July 2020. 16. Kumar S. Managing COVID-19 in Malaysia. Presented at: Combating the COVID-19 Crisis: Today and Beyond; 20 June 2020; KL, Malaysia. 17. Hung IFN,
et al. Lancet 2020;395:1695–1704. 18. Cai Q, et al. Engineering (Beijing) 2020. doi: 10.1016/j.eng.2020.03.007. 19. Wang M, et al. Cell Res 2020;30:269–271. 20. Beigel
JH et al. N Engl J Med 2020. doi: 10.1056/NEJMoa2007764. 21. Yao X, et al. Clin Infect Dis 2020:ciaa237. 22. Mahévas M et al. BMJ 2020;369:m1844. 23. Randomised
Evaluation of COVID-19 Therapy. No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19. Available at: https://www.recoverytrial.net/
news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-
from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19. Accessed 23 July 2020. 24. Herold T, et al. J Allergy Clin Immunol 2020;146:128-136.
e4. 25. Sciascia S, et al. Clin Exp Rheumatol 2020;38:529–532. 26. Xu X, et al. PNAS 2020;117:10970–10975. 27. Wu C, et al. JAMA Intern Med 2020;180:934. 28. Horby P, et
al. medRxiv 2020. 29. Bassetti M, et al. Clin Microbiol Infect 2020;26:880–894. 30. UpToDate. Coronavirus disease 2019 (COVID-19): Hypercoagulability. Available at:https://
www.uptodate.com/contents/coronavirus-disease-2019-covid-19-hypercoagulability#H172461532. Accessed 23 July 2020. 31. Bassetti M. Challenges in Managing
COVID-19. Presented at: Combating the COVID-19 Crisis: Today and Beyond; 20 June 2020; KL, Malaysia. 32. Zhou F, et al. Lancet 2020;395:1054–1062. 33. Pfizer
Malaysia. Pfizer Outlines Five-Point Plan to Battle COVID-19. Available at:https://investors.pfizer.com/investor-news/press-release-details/2020/Pfizer-Outlines-Five-Point-
Plan-to-Battle-COVID-19/default.aspx. Accessed 22 Sep 2020.

For healthcare professionals only

Sponsored as a service to the medical profession by

Pfizer (Malaysia) Sdn Bhd 197801003134 (40131-T) Editorial development by MIMS Medica. The opinions expressed in this publication are not
necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage
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 CONFERENCE COVERAGE
Infectious Disease (IDWeek 2020) Virtual Conference • October 21-25

IDWeek 2020
October 21-25

Asymptomatic COVID-19 individuals carry

similar viral loads as symptomatic patients
PEARL TOH asymptomatic screening, he pointed out. RT-qPCR were spanning wide, the distri-

I
bution was similar between patients with
ndividuals who tested positive for In the cohort study,15,514 staff (mean symptoms and those without — indicat-
COVID-19 but are asymptomatic car- age 45 years, 76 percent female) and ing nasopharyngeal viral load was unre-
ry similar viral loads as symptomat- 16,966 residents (mean age 82 years, lated to symptom status at the time of
ic patients, according to a study on a 65 percent female) at nursing homes testing.
population in nursing homes presented and assisted living facilities underwent
at IDWeek 2020 — underscoring the screening by RT-PCR of nasopharyngeal “In a large cohort of individuals
importance of personal protective equip- swab samples. [IDWeek 2020, abstract screened for SARS-CoV-2 by RT-qP-
ment (PPE) to limit viral transmission. LB-11] CR, we found strikingly similar viral load
distributions in patients with or without
“Up to half of transmission comes Overall, 2,654 residents (15.5 per- symptoms at the time of testing during
from people without symptoms,” said cent) and 624 staff (4.1 percent) turned the local peak of pandemic,” observed
presenting author Dr Roby Bhattacha- out positive for SARS-CoV-2. Bhattacharyya.
ryya from Massachusetts General Hos-
pital in Boston, Massachusetts, US. Among the participants who tested Furthermore, this finding persisted
“Transmission of COVID-19 from people positive, a majority were asymptomatic across all prespecified subgroups exam-
without symptoms confounds public at the time of testing, including 70.8 per- ined, including age, sex, race, and eth-
health containment strategies.” cent of infected residents and 92.4 per- nicity.
cent of infected staff.
Given the wide spectrum of disease “Because the distributions of viral
presentation of COVID-19 — ranging “These findings highlight a role for loads in infected individuals irrespective
from asymptomatic to fatal cases — the testing individuals even though they are of symptomatology are very similar, exist-
investigators were keen to find out what asymptomatic, at least when incidence is ing testing modalities that have been vali-
causes the variability in COVID-19, and high,” said Bhattacharyya. dated for detection of SARS-CoV-2 RNA
whether viral load can explain some of in symptomatic patients should perform
the variability. When analysed by symptom status, similarly in individuals without symptoms
the prevalence of positivity was 12.7 at the time of testing,” Bhattacharyya
“Is nasopharyngeal viral load of percent and 3.7 percent for asymptom- suggested.
SARS-CoV-2 related to symptom status atic residents and staff, respectively,
at the time of testing?” Bhattacharyya compared with 53.1 percent and 18.2 Nonetheless, as there was no lon-
asked during his presentation. percent, respectively among those who gitudinal follow-up, he pointed out that
showed symptoms. whether viral load was related to disease
Answers to this question hold impli- severity in later trajectory of the disease
cations for transmission and the role of Although the range of Ct values of course could not be ascertained.

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 CONFERENCE COVERAGE
Infectious Disease (IDWeek 2020) Virtual Conference • October 21-25

Face shield minimizes SARS-CoV-2 spread,

hospital-acquired infections
JAIRIA DELA CRUZ These favourable results may be at- this period, 112 HCPs tested positive for

W
tributed to a reduction in viral transmis- SARS-CoV-2, with the infection starting
earing of face shields proves sion, according to presenting author Dr in the community then spreading staff-
golden as a preventive mea- Mayar Al Mohajer from the Baylor Col- to-staff, Al Mohajer said. There were
sure, reducing not only the lege of Medicine in Houston, Texas, US. also seven HAIs recorded, which cor-
number of SARS-CoV-2 infections but responded to 3.4 cases per 1,000 pa-
also that of hospital-acquired infections Al Mohajer pointed out that in their tient-days.
(HAIs) among healthcare personnel 500-bed hospital with more than 8,000
(HCPs), as shown in a study reported at HCPs, they had instituted several pre- In response, on July 6, the hospital
IDWeek 2020. ventive measures between April 1 and recommended that all HCPs wear a face
17. HCPs and patients alike masked up. shield upon entry to facility on the basis
At one hospital in Texas, US, the High-risk HCPs underwent surveillance that face shields “reduce the potential of
weekly positivity rate for SARS-CoV-2 testing every 2 weeks, while patients did autoinoculation by preventing the wear-
rose from 0 percent to 12.9 percent in on admission and prior to invasive pro- er from touching their face” and “protect
the preintervention period (April 17–July cedures. Cluster units were also tested the portals of viral entry.”
5), then fell sharply to 2.3 percent fol- weekly.
lowing the implementation of universal Previous studies have shown that
face shield wearing (July 6–26). [IDWeek Not long after, Texas began reopen- this measure effectively reduced imme-
2020, abstract LB-16] ing in three phases. By June 12, which diate viral exposure by 96 percent when
was the last phase, restaurants were op- exposed within 18 inches of a cough
HAI cases followed the same pat- erating at 75 percent capacity while col- source and blocked 68 percent of small
tern, increasing from 0 to 5 in the prein- leges and professional sports capacity particle aerosols, Al Mohajer noted.
tervention period and dropping back to 0 were increased to 50 percent, along with [JAMA 2020;324:1348-1349; J Occup
during the intervention period. other facilities that were open. During Environ Hyg 2014;11:509-518]

Indeed, the intervention resulted

in a significant decline in the predicted
proportion of HCPs contracting SARS-
CoV-2 (18.0 percent to 3.7 percent;
p<0.001) and HAIs (from 8.4 to 1.7 per
1,000 patient-days; p<0.001). “Similar
results were described in community
health workers in India after implemen-
tation of face shields,” he said. [JAMA
2020;324:1348-1349]

“Our findings support universal face

shield use as a part of a multifaceted
approach in areas of high SARS-CoV-2
community transmission,” according to
Al Mohajer.

Face shields are easy to manufac-

ture, which makes them widely avail-
able and cheap, he added. They can
be washed and disinfected and reused
indefinitely.

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 CONFERENCE COVERAGE
Infectious Disease (IDWeek 2020) Virtual Conference • October 21-25

Chlorhexidine oral rinse improves

COPD symptoms
STEPHEN PADILLA and sputum microbiota alpha diversity teobacteria and decreased the content

P
compared with placebo (Shannon di- of Bacteroidetes, TM7, SR1, and Fuso-
atients with chronic obstructive versity index change [standard error], bacteria. [Sci Rep 2020;105254]
pulmonary disease (COPD) seem –0.349 [0.091] and –0.622 [0.169], re-
to benefit from using chlorhexidine spectively; p=0.001 for both). “This shift was associated with a
oral rinses twice daily as shown by the significant decrease in saliva pH and
reduction in oral and sputum microbiota Over the study period, no significant buffering capacity, accompanied by an
alpha diversity and clinically significant change was observed in CRP, fibrinogen, increase in saliva lactate and glucose
improvements in COPD symptoms, ac- WBC count, or BCSS score between levels,” the authors said. “Lower saliva
cording to a study presented at IDWeek groups. and plasma nitrite concentrations were
2020. found after using chlorhexidine, followed
Moreover, chlorhexidine use was as- by a trend of increased systolic blood
On the other hand, “chlorhexidine sociated with a significant improvement pressure.”
use did not result in decreased oral in SGRQ score compared to placebo
or sputum microbiota biomass or de- (mean change, –4.7 vs 1.7; p=0.011; COPD is a progressive lung disease
creased systemic inflammation,” the re- minimal clinically significant difference in that has few available disease-modifying
searchers said. SGRQ score, –4). Adverse events report- therapies. Acute exacerbations of COPD
ed were few. tend to increase morbidity and mortality
A randomized, double-blind, pla- and coincide with sputum and oral mi-
cebo-controlled study was conducted In another study, mouthwash con- crobiota dysbiosis, according to the re-
for 8 weeks to examine the effects of taining chlorhexidine contributed to a searchers of the current study.
twice-daily chlorhexidine oral rinses on major shift in the salivary microbiome,
44 patients with COPD. Of the partici- which led to more acidic conditions and “Oral microbiota also serves as the
pants, 24 (mean age 67.6 years, 8.3 per- lower nitrite availability in healthy individu- source of lower airway microbiota. Ch-
cent female) were assigned to chlorhex- als. Chlorhexidine significantly increased lorhexidine oral rinses are known to alter
idine and 20 (mean age 68.3 years, 5.0 the abundance of Firmicutes and Pro- the oral microbiota,” they added.
percent female) to placebo.

The researchers obtained baseline

and post-treatment data to evaluate
oral and sputum microbiota biomass
and composition, systemic inflammation
(C-reactive protein [CRP], fibrinogen,
and white blood cell [WBC] count), and
respiratory symptoms (ie, breathless-
ness, cough, and sputum scale [BCSS],
St. George’s Respiratory Questionnaire
[SGRQ], and acute exacerbation of
COPD assessment).

Forty patients completed the study.

No significant differences were noted
in oral and sputum microbiota biomass
between the two treatment groups in the
primary analysis. [IDWeek 2020, abstract
634]

Use of chlorhexidine decreased oral

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 CONFERENCE COVERAGE
Infectious Disease (IDWeek 2020) Virtual Conference • October 21-25

Echinocandins boost the

antifungal armamentarium
ELVIRA MANZANO din class is micafungin, approved in

I
Singapore for the treatment of invasive
nvasive fungal infections, particularly candidiasis. It is also approved for use in
those caused by Candida species, are oesophageal candidiasis in patients for
common in hospitalized, immunocom- whom intravenous therapy is an appro-
promised, or critically ill patients and are priate prophylaxis for Candida infection,
associated with considerable morbidity in patients about to undergo allogenic
and mortality. hematopoietic stem cell transplantation,
or in those expected to have neutropenia
Risk factors for invasive candidiasis (absolute neutrophil count < 500 cells/
include prolonged use of broad-spec- μL) for 10 or more days in adults and
trum antibiotics, length of intensive care paediatric patients 4 months or older.
unit (ICU) stay, use of central venous
catheters, receipt of parenteral nutrition, Micafungin exerts its antifungal activ-
neutropenia, use of immunosuppressive ity by inhibiting the synthesis of 1,3-be-
agents, implantable prosthetic devices, ta-D-glucan, an essential component of
and renal replacement therapy. [J Infect fungal cell walls, causing osmotic insta-
Public Health 2014;7:6-19] bility and eventual cell death of the fun- tech company SCYNEXIS, who present-
gus. [Lancet 2003; 362 (9390):1142-51] ed results for the triterpenoid antifungal
Diagnosis and management of inva- agent ibrexafungerp. [IDWeek 2020, ab-
sive candidiasis can be challenging. The The efficacy of micafungin for inva- stract P773]
goal of treatment remains the timely and sive candidiasis has been proven in both
judicious use of safe and efficacious an- adult and paediatric patients [Core Evid “Echinocandins are the first-line treat-
tifungal therapy. 2014; 9:27–39], making it a valuable ad- ment for patients with C. auris infections
dition to the antifungal armamentarium. given the high degree of resistance to
A closer look at azoles and polyenes,” she added. How-
echinocandins Drug-resistant ‘superbugs’ ever, reports of antifungal resistance,
Echinocandins are a class of antifungal Multidrug resistance is uncommon, but even in newer agents such as the echi-
drugs that target the fungal cell wall. increasing reports have occurred in sev- nocandins, further escalate the complex-
They are widely used for invasive candi- eral Candida species, including Candida ity of candidaemia management.
diasis, owing to their wide activity spec- glabrata and recently, Candida auris (C.
trum, favourable toxicity profile, and con- auris). Echinocandin use at
venient dosing, said experts at the recent hospital admission and
IDWeek 2020. C. auris alone has emerged as an discharge
urgent threat. The US Centers for Dis- A pharmacoepidemiologic analysis of
Echinocandins exert antifungal ac- ease Control and Prevention considered echinocandin use at a large quaternary
tivity by inhibiting 1,3-beta-D-glucan this superbug “a serious global health care medical centre in the US showed
synthase. Current guidelines on the threat,’’ preying on hospital and nursing that a significant proportion of echino-
treatment of candidiasis recommend home patients and causing potentially candin courses were started upon hos-
echinocandins as first-line empirical fatal infections that are often unrespon- pital admission and continued after hos-
treatment, with fluconazole as an ac- sive to treatments. pital discharge. [IDWeek 2020, abstract
ceptable alternative in selected patients. P43]
[J Antimicrob Chemother 2018;73(sup- “Candida auris is associated with high
pl_1):i14-i25] mortality … it has the ability to spread Researchers pooled data on echi-
from person-to-person, surface-to-per- nocandin use and clinical microbiologic
Micafungin for invasive son, and could potentiate an outbreak in information from 2017–2019. Monthly
candidiasis healthcare settings,” said Dr Nekhi Azie, days of therapy (DOT) per 1,000 patient
One antifungal agent of the echinocan- VP, Clinical Development, at the US bio- days and the proportion of echinocan-

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 CONFERENCE COVERAGE
Infectious Disease (IDWeek 2020) Virtual Conference • October 21-25

“C. parapsilosis is an emerging drug

resistant pathogen of concern … there is
a need for ongoing antifungal resistance
surveillance among Candida species,”
said presenting author Assistant Profes-
sor Brenda Tesini from the University of
Rochester in Rochester, New York, US at
IDWeek 2020.

“Our data support the empiric use of

echinocandins for C. parapsilosis blood-
stream infections and underscore the
need for antifungal susceptibility testing
[AFST] prior to fluconazole treatment.”

Lower echinocandin
exposure in obese patients
Echinocandin dosing in obese critically
ill patients is a challenging scenario that
has not been fully explored. A systematic
review of studies from PubMed, Embase,
and Cochrane library on micafungin and
other echinocandin agents in obese pa-
din-treated patients with or without pos- tients (≥BMI 30) showed that there was a
itive Candida cultures were calculated. nocandin courses were continued until correlation between obesity and increas-
The relationship between echinocandin discharge. ing systemic clearance, and reduced ex-
use and hospital admission and dis- posure with micafungin.
charge dates were also evaluated. “Further studies evaluating potential
benefits of long-acting echinocandins, Some studies reported even lower
Echinocandin monthly DOT per with an emphasis on transition of care, systemic exposure with a BMI >40. [ID-
1,000 patient days averaged 26 and are warranted,” concluded Jinhee. Week 2020, abstract P1159]
DOT did not change considerably during
the entire period. Of the patients with Empiric use Caspofungin and anidulafungin ex-
microbiologic evidence of Candida, 842 of echinocandins posures were also reduced in obese pa-
or 51 percent were treated with echino- Meanwhile, a US surveillance study on tients.
candins. the antifungal susceptibility patterns
of C. parapsilosis showed that no re- “Adequate antifungal exposure is the
“Length of echinocandin therapy sistance was detected to caspofungin key to successful treatment, and there
was significantly longer in patients with (MIC50 0.25) or micafungin (MIC50 1.00), are several factors that can influence
positive Candida cultures (5.5 days) with one (<1 percent) isolate resistant exposure of echinocandin antifungal
vs those without positive cultures (3.9 to anidulafungin (MIC50 1.00). [IDWeek agents,” said presenting author Dr Yazed
days; p<0.001),” said presenting author 2020, abstract P146] Alsowaida, Pharmacy Resident, Brigham
Dr Jinhee Jo, a post-doctoral Infectious and Women’s Hospital, Brookline, Mas-
Diseases Fellow from the University of In contrast, 84 (6.3 percent) isolates sachusetts, US.
Houston in Houston, Texas, US. were resistant to fluconazole and anoth-
er 44 (3.3 percent) isolates had dose-de- “There is now consistent evidence
Of 1,659 echinocandin courses pendent susceptibility to fluconazole showing lower echinocandins expo-
evaluated, 549 courses (33 percent) (MIC50 1.00). Fluconazole resistance sure in obese patients. More studies are
were initiated within 2 days of hospital increased sharply from an average of 4 needed to determine the outcomes of
admission. Average time from hospital percent during 2008-2014 to a peak of fungal infections in obese patients, and
admission to echinocandin initiation was 14 percent in 2016 and declined to 6 probably the need for dose adjustment in
9 days. A total of 505 (24 percent) echi- percent in 2018. this population.”

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DOCTOR || DECEMBER ISSUE
 Sponsored Symposium Highlights

From clinical trials to real-world evidence:

Tofacitinib in the treatment of rheumatoid arthritis
Janus kinase inhibitors (JAKIs) have emerged as an effective class of therapy for rheumatoid
arthritis (RA).1 At the EULAR virtual symposium, a group of specialists discussed recent updates
on tofacitinib (Xeljanz®, Pfizer) – the first-in-class JAKI for the treatment of RA.

Axel Finckh, MD Joel Kremer, MD Paul Bird, MD, PhD

University of New South Wales
Geneva University Hospital, Albany Medical College,
Sydney, Australia
Geneva, Switzerland Albany, NY, USA

The first-in-class JAKI for RA Reaffirming the real-world safety data of tofacitinib
The introduction of JAKIs for the treatment of RA adds to the Herpes zoster infections are characteristic of tofacitinib therapy
armamentarium of DMARDs. Currently, three JAKIs are approved Pooled data for incidence rates (IRs) of serious infections (SI) in
for RA: tofacitinib, baricitinib and upadacitinib.2 Tofacitinib is the tofacitinib RA trials (phases II, III and IV) which used adalimumab
first JAKI to be approved for the treatment of moderate-to-severe as an active control reported that the risk of SI was typically higher
RA,3 and it is administered as a monotherapy or combination in patients ≥65 years across all active treatment arms (ie, tofacitinib
therapy with nonbiologic DMARDs – mainly methotrexate (MTX) 5 mg and 10 mg BID and adalimumab) compared with younger
– in patients with inadequate response, or intolerance to one or patients.10 Nevertheless, when patients were stratified by age, IRs
more csDMARD.4 were similar across the active treatment groups.10

Tofacitinib has been extensively studied in the ORAL programme In the real-world setting, a multi-database (Medicare, Optum,
in patients with moderate-to-severe RA who are responding MarketScan) study in the US analysed the risk of SI among patients
inadequately to MTX (ie, ORAL STANDARD, SCAN, STRATEGY), with RA receiving tofacitinib compared with seven other bDMARDs.
csDMARDs (ie, ORAL SOLO and SYNC), and biologics (ie, ORAL IRs of SI with tofacitinib were similar to those of adalimumab and
STEP).5 The integrated safety analysis from phase III studies certolizumab, but was lower than that of infliximab.11 Findings from
reported similar safety profiles between tofacitinib and bDMARDs.6 the study also reported that tofacitinib was associated with a two-
fold higher risk of herpes zoster than bDMARDs.11
The value of RWE in RA
No increased risk of VTE with tofacitinib compared with other
Randomised controlled trials (RCTs) have been the cornerstone
therapies
of evidence-based medicine.7 However, the highly controlled
Venous thromboembolic events (VTE) have been identified as an
environment in RCTs compromises the external validity and reduces
the generalisability of trial findings in real-world patients; therefore, important risk factor associated with the use of JAKI.12 A review
evidence gathered in real-life settings complements the data of RCT data for tofacitinib in RA, along with other diseases (ie,
gathered in RCTs by contributing to the overall risk-benefit profile psoriasis, psoriatic arthritis, and ulcerative colitis), showed no
of a drug.7 Key sources of real-world data include insurance claims significant increase in the risk of either deep vein thrombosis (DVT)
databases and disease registries.7 or pulmonary embolism (PE) compared with adalimumab or MTX
(Fig 1).13 However, a recent analysis of the ORAL Surveillance data
(A3921133), an ongoing study evaluating the effect of tofacitinib 5
Tofacitinib: A valuable treatment option for RA and 10 mg BID versus TNFi in patients with RA (ie, ≥50 years old
The OPAL dataset reflects the real-world treatment of RA in with ≥1 CV risk factor), revealed a significantly higher occurrence
Australian patients. Analysis of the disease activity outcomes from of PE – approximately 6-fold increase – with tofacitinib 10 mg BID
March 2015 to September 2018 showed similar remission rates compared with TNFi .14 It is important to note that the use of 10 mg
(based on DAS28-ESR, SDAI and CDAI) between tofacitinib tofacitinib BID is not approved for the treatment of RA in Malaysia.4
and bDMARDs over 18 months of treatment.8 Interestingly, more
patients were prescribed tofacitinib as monotherapy compared Real-world observations from the CORRONA registry revealed
with bDMARDs.8 similar rates of VTE in patients treated with tofacitinib compared
with those receiving bDMARDs (Fig 2), 15 while data collected from
Similar persistence between tofacitinib and bDMARDs was also MarketScan and Medicare showed nonsignificant differences, albeit
observed in other real-world studies. Analysis of a population- a numerically higher risk of VTE in patients taking tofacitinib versus
based cohort within the Swiss RA registry, SCQM, compared those treated with TNFi for RA.16
drug maintenance of three alternative treatment options
for RA, namely TNFi, biologics with other modes of action
(bDMARD-OMA), and tofacitinib. The overall drug maintenance
No indication of increased risk for MACE,
for tofacitinib was significantly higher than TNFi (HR, 1.29; malignancy and mortality
95% CI, 1.14–1.47; p<0.001), but similar with bDMARD-OMA. 9 Consistent with the safety data established in clinical trials, the
Interestingly, patients on TNFi were most likely to discontinue CORRONA registry reported similar rates of major cardiovascular
treatment because of ineffectiveness, while patients who were events (MACE),15 nonmelanoma skin cancer (NMSC), malignancies
on tofacitinib appeared to have increased discontinuation rates (excluding NMSC), and death in patients with RA receiving tofacitinib
due to intolerance. 9 compared with bDMARDs.17
 Sponsored Symposium Highlights

Fig 1. Incidence of VTE in tofacitinib RCTs in patients with RA13

6 DVT PE
Incidence rate 5
4
3
2
1 0.70
0.10 0.10 0.00 0.10 0.20 0.00 0.00
0
Tofacitinib Tofacitinib Adalimumab Methotraxate Tofacitinib Tofacitinib Adalimumab Methotraxate
5 mg BID 10 mg BID† 5 mg BID 10 mg BID†
n 1 1 0 2 2 3 0 0
PY 1849 2024 257 223 1849 2024 257 223
Excluding ORAL Surveillance trial data (A3921133). Incidence rates are events/100 patient-years (PY; 95% CI).
†
Tofacitinib 10 mg BID is not the approved dosage in Malaysia for the treatment of RA.
Figure adapted from Mease PJ, et al. 2017 ACR/ARHP Annual Meeting. Abstract 16L.13

Fig 2. Incidence of VTE, including DVT and PE, in patients with RA initiating tofacitinib or bDMARDs based on data from the
CORRONA registry15

1 VTE‡ DVT PE

0.8
Incidence rate

0.6
0.4
0.33
0.2 0.19 0.19 0.18
0.14
0.05
0
Tofacitinib bDMARDs Tofacitinib bDMARDs Tofacitinib bDMARDs
n 4 30 1 17 3 16
PY 2136.4 9879.3 2137.9 9892.0 2136.7 9891.8
Incidence rates (IRs) are events/100 patient-years (PY; 95% CI).
‡
VTE (DVT and PE combined) data did not have ≥80% power to detect a hazard ratio of ≤2.25 between cohorts, therefore propensity scores were not calculated; data presented are age- and gender
standardised IRs.
Figure adapted from Kramer J et al. 2019 ACR/ARP Annual Meeting. Abstract 2372.15

Key takeaways
● Tofacitinib as a monotherapy or combination therapy is effective in reducing the signs and symptoms of RA.4
● Based on published RCTs, tofacitinib as an add-on to MTX is at least as effective as adding TNFi to MTX for the treatment of moderate-
to-severe RA.18
● RWE to date has shown no indication of increased risk of SI, VTE, MACE, malignancies (excluding NMSC), NMSC and death with
tofacitinib compared with bDMARDs, apart from HZ infections.15,17

*Upadacitinib is currently not approved for use in Malaysia.

†
Tofacitinib 10 mg BID is not the approved dosage in Malaysia for the treatment of RA.
‡
Tofacitinib is not indicated for the treatment of psoriasis, psoriatic arthritis, and ulcerative colitis.
EULAR: European League Against Rheumatism; ORAL: The Oral Rheumatoid Arthritis Trial; CORRONA: Consortium of Rheumatology Researchers of North America; OPAL-QUMI: Optimising Patient outcomes
in Australian rheumatology – Quality Use of Medicines Initiative; SCQM: Swiss Clinical Quality Management in Rheumatic Diseases.

DMARD: Disease modifying antirheumatic drugs; TNFi: tumor necrosis factor inhibitor; csDMARD: conventional synthetic DMARD (eg, methotrexate hydroxychloroquine); bDMARD: biologic DMARD/biologics
(eg, TNFi: adalimumab, certolizumab, infliximab; OMA: abatacept, rituximab); CV: cardiovascular; DAS28-ESR: disease activity score-28 with erythrocyte sedimentation rate; CDAI: clinical disease activity index;
SDAI: simple disease activity index; HR: hazard ratio; CI: confidence interval; BID: twice daily.

References: 1. Dowty ME, et al. Pharmacol Res Perspect 2019;7:e00537. 2. Medicine Matter. JAK inhibitors in RA: A round-up of the phase 3 trials. Available at: https://rheumatology.medicinematters.com/
rheumatoid-arthritis-/jak-inhibitors/jak-inhibitors-in-ra/16584004. Published July 2020. Accessed 28 July 2020. 3. Medscape. FDA Approvals: Tofacitinib for Rheumatoid Arthritis. Available at: https://www.
medscape.org/viewarticle/775016. Published 29 November 2012. Accessed 5 August 2020. 4. Tofacitinib Citrate (Prescribing Information). Malaysia, Pfizer; 2020. 5. Kucharz EJ et al. Reumatologia 2018;56:203–
211. 6. Vieira MC, et al. Clin Ther 2016;38:2628–2641.e5. 7. Katkade VB et al. J Multidiscip Healthc 2018;11:295–304. 8. Bird P,et al. Clin Rheumatol 2020; 39:2545–2551. 9. Finckh A, et al. RMD Open 2020;6: e001174.
10. HCP Live. Serious infections more likely in older rheumatoid arthritis patients. Available at:https://www.hcplive.com/view/tocilizumab-not-meet-endpoint-covid-19-phase-3-trial. Published 7 June 2020.
Accessed 3 August 2020. 11. Pawar A, et al. Lancet Rheumatol 2020;2:e84-e98. 12. Jawad Bilal, et al. Risk of Thromboembolism with Janus Kinase Inhibitors: A Systematic Review and Meta-Analysis of Randomized
Placebo Controlled Trials. Presented at: 2019 ACR/ARP Annual Meeting; 8–13 November 2019; Atlanta, GA. Abstract 2393. 13. Mease PJ, et al. Incidence of Thromboembolic Events in the Tofacitinib Rheumatoid
Arthritis, Psoriasis, Psoriatic Arthritis and Ulcerative Colitis Development Programs Presented at: 2017 ACR/ARHP Annual Meeting; 3–8 November 2017 in San Diego, CA. Abstract 16L. 14. RheumNow. EMA Final
Recommendations on VTE Risk with Tofacitinib. Published 10 March 2020. Accessed 4 August 2020. Available at: https://rheumnow.com/content/ema-final-recommendations-vte-risk-tofacitinib. 15. Kremer J,
et al. Post-approval comparative safety study of tofacitinib and biologic dDMARDs: Five–year results from a US-based rheumatoid. Presented at: 2019 ACR/ARP Annual Meeting; 8–13 November 2019; Atlanta,
GA. Abstract 2372. 16. Desai RJ, et al. Arthritis Rheumatol 2019;71:892–900. 17. Kremer J, et al. Comparison of Malignancy and Mortality Rates Between Tofacitinib and Biologic DMARDs in Clinical Practice: Five-
Year Results from a US-Based Rheumatoid Arthritis Registry. Presented at: 2019 ACR/ARP Annual Meeting; 8–13 November 2019; Atlanta, GA. Abstract 2874. 18. Fleischmann R, et al. Lancet 2017;390:457–468.

For healthcare professionals only

Please refer to the abbreviated product information on the advertisement page.
Full prescribing information for tofacitinib (Xeljanz®) is available on request.

Pfizer (Malaysia) Sdn Bhd 197801003134 (40131-T) Editorial development by MIMS Medica. The opinions expressed in this publication are not
Level 10 & 11, Wisma Averis , Tower 2, Avenue 5, necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or
damage howsoever arising is hereby disclaimed. ©2020 MIMS Medica. All rights reserved. No
Bangsar South, No. 8, Jalan Kerinchi, 59200 Kuala Lumpur. part of this publication may be reproduced by any process in any language without the written
Tel : (03) 2281 6000 Fax : (03) 2281 6388 permission of the publisher. Enquiries: MIMS Medica Sdn Bhd (891450-U), 2nd Floor, West Wing,
www.pfizer.com.my Quattro West, No.4, Lorong Persiaran Barat, 46200 Petaling Jaya, Selangor, Malaysia.
Tel: (603) 7623 8000 Fax: (603) 7623 8188
Email: enquiry.my@mims.com Website: www.mims.com
PP-XEL-MYS-0384-09SEP2020 MY-PFI-468
 In the treatment of adults with
THE FIRST ORAL JAK INHIBITOR MODERATE TO SEVERE
APPROVED FOR RA*1,2 RHEUMATOID ARTHRITIS (RA)

A MARK OF
PROVEN
EFFICACY XELJANZ – provides proven, rapid,
and sustained efficacy
with AND without methotrexate.3-5,a

a
As measured by the primary endpoints of ACR20 at month 3 (ORAL Solo) and month 6
(ORAL Standard), ACR50 at month 6 (ORAL Strategy); supported by analyses at week 2
(ORAL Solo) and out to year 2.3-5

ACR=American College of Rheumatology; JAK=Janus kinase.

* First as per US FDA approval.

References: 1. U.S. Food and Drug Administration approves Pfizer’s XELJANZ® (tofacitinib citrate) for adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate [press release]. New York, NY: Pfizer Inc; November 7, 2012. http://press.pfizer.
com/press-release/multimedia-us-food-and-drug-administration-approves-pfizers-xeljanz-tofacitinib-citrat. Accessed July 23, 2020. 2. XELJANZ/XELJANZ XR [prescribing information]. New York, NY: Pfizer Inc; December 2017. 3. Fleischmann R, Kremer J, Cush J, et al; for the ORAL Solo Investigators. Placebo-controlled
trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;267(6):495-507. 4. van Vollenhoven RF, Fleischmann R, Cohen S, et al; for the ORAL Standard Investigators. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508-519. 5. Fleischmann R, Mysler E, Hall S,
et al; for the ORAL Strategy Investigators. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet. 2017;390(10093):457-468.

XELJANZ Abbreviated Package Insert

Formulation/Presentation: XELJANZ (tofacitinib) film-coated tablet, 5mg; packing of 56’s. Indications: Treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with
methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs). Not recommended to use in combination with biologic DMARDs or potent immunosuppressants, such as azathioprine and cyclosporine. Dosage: 5 mg administered twice daily. Dosage should be reduced to 5 mg once daily in
patients with moderate or severe renal impairment and in patients with moderate hepatic impairment. For patients undergoing hemodialysis, dose should be administered after the dialysis session on dialysis days. If a dose was taken before the dialysis procedure, supplemental doses are not recommended in patients after
dialysis. Not recommended to use in patients with severe hepatic impairment. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Special Warnings & Precautions: Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic
pathogens. Common serious infections reported: pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis and appendicitis. Patients should be evaluated and tested for latent or active tuberculosis prior to treatment. Tuberculosis and other mycobacterial infections, cryptococcus, histo plasmo sis,
esophageal candidiasis, multidermatomal herpes zoster, cytomegalovirus infection, BK virus infections and listeriosis. Monitor signs and symptoms of infection and TB. Should not be initiated in active infection. Event of interstitial lung disease reported. Malignancies. Viral reactivation, Hepatitis B reactivation; herpes
virus reactivation (eg: herpes zoster)-risk of herpes zoster appeared to be higher in Japanese and Korean patients treated with tofacitinib, screening for viral hepatitis. Lymphomas, non-melanoma skin cancers. Periodic skin examination is recommended for those at increased risk of skin cancer. Discontinue tofacitinib in
patients with symptom of thrombosis. Patients that may be at increased risk of thrombosis should be avoided. Gastrointestinal perforation. Reactions such as angioedema and urticaria that may reflect drug hypersensitivity have been observed. Laboratory parameters (lymphocyte, neutrophil, hemogloblin, lipids). Not
recommended to give concurrently with live vaccines. Caution in patients with history of chronic lung disease. Tofacitinib should not be used during pregnancy unless clearly necessary. Women of reproductive potential should be advised to use effective contraception during treatment and for at least 4 weeks after
the last dose. Women should not breast-feed while treated with tofacitinib and for at least 18 hours after the last dose of tofacitinib. Caution in elderly and diabetic. Adverse Reactions: Pneumonia, cellulitis, herpes zoster, urinary tract infection, diarrhea, nasopharyngitis, upper respiratory tract infections, headache,
hypertension, liver enzymes elevation, lipid elevations, serurm creatinine elevation, anemia, diverticulitis, dehydration, insomnia, paresthesia, dyspnea, cough, sinus congestion, interstitial lung disease, abdominal pain, dyspepsia, vomiting, gastritis, nausea, hepatic steatosis, rash, erythema, pruritus, musculoskeletal
pain, arthralgia, tendonitis, joint swelling, non-melanoma skin cancer, thrombosis, pyrexia, fatigue, peripheral edema. The most common types of malignancy were lung and breast cancer, followed by gastric, colorectal, renal cell, prostate cancer, lymphoma, malignant melanoma, pancreatic cancer
API-Xeljanz-0520

FULL PRESCRIBING INFORMATION IS AVAILABLE UPON REQUEST.

Pfizer (Malaysia) Sdn Bhd 197801003134 (40131-T)

Level 10 & 11, Wisma Averis , Tower 2, Avenue 5, Bangsar South, No. 8, Jalan Kerinchi, 59200 Kuala Lumpur.
Tel : (03) 2281 6000 Fax : (03) 2281 6388 www.pfizer.com.my PP-XEL-MYS-0342-24JUL2020

FOR HEALTHCARE PROFESSIONALS ONLY

 CONFERENCE COVERAGE
Infectious Disease (IDWeek 2020) Virtual Conference • October 21-25

Oral sulopenem shows promise said Dunne, who called for further investi-

for uncomplicated UTI

gation into the impact of ASB on treatment
outcomes in this setting.

AUDREY ABELLA According to Dunne, these results may Quinolone-resistant +

T
have been driven by the lower rates of mi- susceptible pathogens =
he SURE*-1 trial demonstrated the crobiologic failure (18 percent vs 27 per- sulopenem noninferiority
potential of a novel, broad-spectrum cent) and rescue antibiotic use (0 percent In the combined analysis which, according
penem antibiotic – sulopenem et- vs 8 percent) in the sulopenem vs the cip- to Dunne, is most reflective of what a prac-
zadroxil/probenecid – for women with un- rofloxacin arm. ticing clinician faces when seeing patients
complicated urinary tract infection (uUTI). with uUTI, ORRs for sulopenem and cipro-
“[It is important to] point out that … floxacin were similar at ToC (66 percent vs
“[Compared with ciprofloxacin,] su- 5 percent of women in this [cohort had] 68 percent), suggesting the noninferiority
lopenem was superior [in women] with a uropathogen that was resistant to all of the former to the latter. At EoT, ORR was
quinolone-resistant uropathogen and not four major classes of oral antibiotics,” a little better for sulopenem (65 percent vs
noninferior [in] patients with quinolone-sus- stressed Dunne. Yet, ORRs consistent- 56 percent; p=0.006), which could have
ceptible uropathogen,” said Dr Michael ly favoured sulopenem over ciprofloxacin been driven by the ORRs observed in the
Dunne from Iterum Therapeutics, Old Say- across all pathogen subsets (67 percent quinolone-resistant subset.
brook, Connecticut, US. “In a combined vs 36 percent; p<0.001 [β-lactam-resis-
analysis without regard to quinolone sus- tant], 58 percent vs 32 percent; p=0.012 Apart from the higher rate of microbi-
ceptibility, sulopenem was noninferior to [ESBL***-positive], 65 percent vs 36 per- ologic failure with sulopenem vs ciproflox-
ciprofloxacin.” cent; p<0.001 [TMP-SMX#-resistant], and acin at ToC (14 percent vs 10 percent),
77 percent vs 42 percent; p=0.002 [nitro- results in both arms were generally similar
A total of 1,671 women** (median age furantoin-resistant]). (11 percent vs 10 percent [clinical failure]
54 years) were randomized 1:1 to receive and 4 percent vs 5 percent [both clinical
sulopenem 500 mg/probenecid 500 mg The findings from this cohort provide and microbiologic failure]).
BID for 5 days and placebo ciprofloxacin substantial evidence reflecting the treat-
for 3 days, or ciprofloxacin 250 mg BID ment effect of sulopenem in patients with The slightly higher ASB rate with su-
for 3 days and placebo sulopenem for 5 uUTI, noted Dunne and colleagues. lopenem vs ciprofloxacin (14 percent vs 10
days. Of these, 1,071 had a uropathogen percent) might have been carried over from
identified on culture. From this cohort, two Quinolone-susceptible that observed in the quinolone-susceptible
independent subgroups were evaluated pathogens: sulopenem worse? population, noted Dunne.
based on organisms that were either resis- In this cohort, sulopenem was not nonin-
tant or susceptible to quinolones. Overall ferior to ciprofloxacin in terms of ORR at Overall, treatment-emergent adverse
response rates (ORRs; ie, both clinical and ToC (67 percent vs 79 percent). However, events (TEAEs) were higher with sulopen-
microbiologic success) were evaluated at ORRs were similar at EoT (65 percent for em vs ciprofloxacin (25 percent vs 14 per-
days 5 (end-of-treatment [EoT]) and 12 both). cent), the most common being diarrhoea
(test-of-cure [ToC]). [IDWeek 2020, ab- (12 percent vs 3 percent). However, most
stract LB-1] “[The difference suggests that] some- were mild and self-limiting. Serious TEAE
thing is occurring between EoT and ToC,” rates were similar (0.7 percent vs 0.2 per-
Quinolone-resistant Dunne pointed out. Indeed, there was a cent).
pathogens: sulopenem beats higher rate of asymptomatic bacteriuria
ciprofloxacin (ASB) with sulopenem vs ciprofloxacin (13 Sulopenem is being developed for
Sulopenem was superior to ciprofloxacin in percent vs 4 percent), which could have multidrug-resistant infections. If approved,
terms of ORRs, both at EoT (65 percent vs contributed to the lower microbiologic suc- sulopenem will be the first oral penem anti-
30 percent) and ToC (63 percent vs 36 per- cess rate with the former vs the latter (78 biotic for uUTI, noted the researchers.
cent; p<0.001 for both). Independent eval- percent vs 89 percent).
uation of clinical and microbiologic success * SURE: SUlopenem for Resistant Enterobacteriaceae
** Inclusion criteria: At least two signs/symptoms of
rate at ToC also reflected the superiority of “ASB occurred more commonly with uUTI (ie, urinary frequency, urinary urgency, pain or
sulopenem to ciprofloxacin (83 percent vs sulopenem than ciprofloxacin … and that burning on micturition, suprapubic pain), positive
urinalysis, evidence of pyuria
63 percent [clinical] and 74 percent vs 50 really accounted for the biggest difference *** ESBL: Extended-spectrum β-lactamase
percent [microbiologic]; p<0.001 for both). in the outcome in this group of patients,” # TMP-SMX: Trimethoprim/sulfamethoxazole

27
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Society of Nephrology (ASN) Kidney Week 2020 • October 20-25

ASN Kidney
Week 2020
October 20-25

Icosapent ethyl shows consistent benefit

in statin-treated patients
AUDREY ABELLA n=4,455), and ≥90 mL/min/1.73 m2 (G1; 0.66, respectively). “[However,] the study

T
n=1,902). [ASN Kidney Week 2020, ab- was not specifically powered to identify
he REDUCE-IT* RENAL study, a stract FR-OR18] differences within these categories,” said
substudy of the REDUCE-IT trial, Majithia.
reflected the consistent benefit of Looking at the primary endpoint by
icosapent ethyl (IPE) in statin-treated pa- baseline eGFR, the IPE benefit seen in Regarding the key secondary end-
tients with established** cardiovascular the overall population (hazard ratio [HR], point, there was again a consistent, sig-
disease (CVD) or diabetes, regardless of 0.75) appears to be sustained in each nificant benefit across all eGFR catego-
eGFR*** status. eGFR category (HRs, 0.71, 0.80, and ries with IPE vs placebo (HRs, 0.71, 0.77,
0.70 for G3, G2, and G1, respectively). and 0.70 for G3, G2, and G1, respective-
“In REDUCE-IT RENAL, both pri- ly), which mirrored that seen in the overall
mary# and secondary## endpoint event “[W]e observed early, consistent, and cohort (HR, 0.74). As in the primary end-
rates increased with decreasing eGFR. sustained separation in primary endpoint point, ischaemic CV event rates with IPE
[Nonetheless,] relative risk reductions event rates,” said Majithia. were higher in the G3 (17 percent) vs the
(RRRs) were similar with IPE vs placebo G2 and G1 arms (10 percent and 8 per-
… across a broad range of eGFR cate- Notably, CV event rates with IPE cent, respectively). ARR was also higher
gories,” said Dr Arjun Majithia from the were higher in the G3 vs the G2 and G1 in the G3 arm (6 percent vs 3 percent
Brigham and Women’s Hospital, Boston, arms (22 percent vs 17 percent [G2] and [both G2 and G1]); RRRs were similar
Massachusetts, US, who presented the 13 percent [G1]). Absolute risk reduc- across all categories (29, 23, and 30 per-
findings. tion (ARR) was greater in the G3 arm cent, respectively). The corresponding p
(7 percent vs 4 percent and 5 percent), values for G3, G2, and G1 were 0.001,
“Chronic kidney disease is associat- but RRRs were similar across all eGFR 0.002, and 0.02, respectively.
ed with adverse outcomes amongst pa- categories (29, 20, and 30 percent for
tients with established CVD or diabetes,” G3, G2, and G1, respectively). RRR in Post hoc analysis of the secondary
he noted. The findings thus underline the G3 was highly statistically significant endpoint also revealed consistent ben-
potential benefit of IPE in this setting, as (p=0.0002); p values for G2 and G1 were efits with IPE including patients with the
“several widely available CV medications 0.001 and 0.003, respectively. lowest eGFR category of 15–30, Majithia
for the treatment of CVD [in] patients with noted.
low eGFR may be ineffective.” In a post hoc analysis further stratify-
* REDUCE-IT: REDUction of Cardiovascular Events
ing patients according to eGFR catego- with icosapent ethyl – Intervention Trial
Data on the >8,000 REDUCE-IT pa- ries corresponding to CKD stage, there ** Stable coronary disease, peripheral artery disease,
or cerebrovascular disease
tients receiving either IPE 4 g daily or were consistent CV event reductions in *** eGFR: Estimated glomerular filtration rate
placebo were stratified into three eGFR IPE vs placebo recipients with eGFRs of # Composite of CV death, nonfatal MI, nonfatal
stroke, coronary revascularization, and unstable
categories: <60 mL/min/1.73 m2 (G3; ≥15 to <30, ≥30 to <45, and ≥45 to <60 angina
n=1,816), 60–90 mL/min/1.73 m2 (G2; mL/min/1.73 m2 (HRs, 0.59, 0.83, and ## Composite of CV death, MI, and stroke

30
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Society of Nephrology (ASN) Kidney Week 2020 • October 20-25

More protein of no help to group or the intensive ONS group. Pa-

haemodialysis patients?
tients following standard nutrition pro-
tocol received ONS during the first 120
days of dialysis and thereafter, continued
PEARL TOH Medical Center in Boston, Massachu- ONS only if they had poor nutritional sta-

A
setts, US. tus (serum albumin levels ≤3.5 g/dL). On
dding nutritional supplements, the other hand, those in the intensive
particularly protein, to diet of pa- “I think it’s really, really important to ONS group received supplements during
tients undergoing haemodialysis say that [the study] doesn’t tell us any- every haemodialysis session regardless
does not give an edge in survival com- thing about giving protein supplements of their serum albumin levels.
pared with standard nutritional supple- to people with low serum albumin,” said
ments, according to the HELPS-HD* Weiner, pointing out that this may still be The intensive group consumed ap-
study. a good practice based on data from ob- proximately twice as many supplements
servational studies. than the standard group, Weiner pointed
During a median follow-up of 2 years, out.
patients who received intensive oral nu- “So, this doesn’t speak to people
tritional supplements (ONS) were no with low serum albumin, it only speaks to “The most common things that were
more likely to survive than those follow- people with more normal serum albumin used were simple protein bars. Things
ing standard nutritional protocol (hazard levels,” he explained. that taste good that people would be
ratio [HR], 1.02, 95 percent confidence happy to eat,” explained Weiner. In gen-
interval [CI], 0.92–1.14). [ASN Kidney What’s in the supplements? eral, protein bars constituted half of the
Week 2020, abstract FR-OR55] As haemodialysis is a stressful process nutritional supplements, with the aim of
for the body, supplementing protein having 15–20 g of protein — thus high-
Death rates were similar at 35.8 per- during dialysis appears to help patients lighting protein as the main source of nu-
cent in the intensive ONS group com- with poor nutrition. However, whether trition.
pared with 36.5 percent in the standard this practice also benefits patients with
nutrition group. normal nutritional status is unclear — The supplements were made up of
until results from the HELPS-HD study food that were easily available in the su-
“The findings suggest that giving came to light. permarkets in order for them to be scal-
protein supplements at dialysis to hae- able in the real world if the results turned
modialysis patients with more normal In the cluster-randomized pragmat- out positive.
nutritional status does not lower the risk ic trial, 10,457 haemodialysis patients
of death in haemodialysis patients,” said (median age 63 years, 56 percent men) “[Nonetheless,] there’s no difference
lead author Dr Daniel Weiner of Tufts were assigned to the standard nutrition in mortality outcomes between an in-
tensive and ONS protocol,” concluded
Weiner, who cautioned that this does not
necessarily apply to patients with poor
nutritional status.

“No conclusion can be drawn regard-

ing patients with low albumin on the utili-
ty of ONS,” he stated.

Analyses are currently ongoing to

evaluate the role of factors such as base-
line albumin levels and key subgroups in
the association with mortality, as well as
other outcome such as hospitalization,
according to Weiner.

* HELPS-HD: Health Effects of oraL Protein Supple-

ments in HD

31
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Society of Nephrology (ASN) Kidney Week 2020 • October 20-25

Glomerular disease tied to increased CVD risk

ROSHINI CLAIRE ANTHONY cent CI, 2.12–2.82). This risk was highest

A
among patients with FSGS (SIR, 3.98,
dults with glomerular disease 95 percent CI, 3.19–4.91), followed by
have a more than twofold risk of membranous nephropathy (SIR, 3.03, 95
cardiovascular (CV) events com- percent CI, 2.23–4.03), minimal change
pared with the general population, with disease (SIR, 1.76, 95 percent CI, 1.03–
the risk varying by type of glomerular dis- 2.82), and IgA nephropathy (SIR, 1.38,
ease, according to a retrospective study 95 percent CI, 1.01–1.85).
presented at ASN Kidney Week 2020.
“Chronic kidney disease (CKD) is as-
The researchers identified 1,912 sociated with increased CV risk,” said
adults (median age 50.6 years, 59.5 Gunning. While proteinuria and reduced
percent male) with glomerular disease eGFR are strong, independent CV risk
from a centralized kidney pathology reg- factors, patients with glomerular disease
istry between 2000 and 2012 in British may have an additional risk due to ne-
Columbia, Canada. These included in- phrotic syndrome, systemic inflamma-
cidents of focal segmental glomerulo- tion, endothelial dysfunction, and im-
sclerosis (FSGS; n=540), IgA nephropa- munosuppressive therapies, she said.
thy (n=759), membranous nephropathy However, there is little data on CV risk in
(n=387), and minimal change disease 1.7–3.9) and FSGS (HR, 3.7, 95 per- the different types of glomerular disease.
(n=226). Patients with end-stage kidney cent CI, 2.6–5.3; p<0.01 for both), but
disease (ESKD) at biopsy were excluded. not minimal change disease (HR, 1.3, 95 “These results demonstrate that …
percent CI, 0.8–2.4; p=0.29), were asso- patients with glomerular disease are
A hospital discharge registry was ciated with a higher risk of CV events. at high risk of cardiovascular disease
used to assess the primary outcome (CVD), both before and after ESKD onset
which was a composite of major ad- Traditional CV risk factors were also … with 10-year risk exceeding 10 per-
verse CV events or revascularization significantly associated with an increased cent,” said Gunning.
procedure, including coronary artery, CV risk, as were proteinuria and esti-
cerebrovascular, and peripheral vascular mated glomerular filtration rate (eGFR). The CV risk for all glomerular disease
disease. Patients were followed up for a However, in the multivariable analysis, subtypes was higher than the general
median 6.8 years during which time 338 the significance was lost for multiple fac- population,” said Gunning and co-au-
CV events occurred. tors, including glomerular disease type, thors. This highlights the need for CVD
though proteinuria (HR, 1.3 per dou- prevention strategies in patients with glo-
The overall risk of CV events at 10 bling of g/d) and eGFR (HR, 0.8 per 15 merular disease.
years was 16 percent, with an event rate mL/min/1.73 m2) remained significant
of 24.7 per 1,000 person-years. This (p<0.01 for both). “Consideration of glomerular dis-
risk varied by glomerular disease type ease-specific factors can help improve
with the highest risk noted with FSGS This suggests that the increased CV CV risk prediction. Failure to take these
(27.0 percent), followed by membranous risk among these patients cannot be fully novel factors into account will lead to un-
nephropathy (19.4 percent), minimal explained by traditional CV risk factors, derestimation of CV risk and underutiliza-
change disease (13.2 percent), and IgA where some of the risk is accounted for tion of CV primary prevention strategies,”
nephropathy (7.7 percent), with event by proteinuria and eGFR, said lead au- Gunning noted.
rates of 46.1, 26.4, 16.4, and 12.2 per thor Heather Gunning from the University
1,000 person-years, respectively. [ASN of British Columbia in Vancouver, Cana- Research is ongoing to examine the
Kidney Week 2020, abstract SA-OR36] da. effect of long-term glomerular disease
activity and immunosuppressive treat-
Univariate analysis showed that Patients with glomerular disease also ment on CV risk. “This will allow better
compared with IgA nephropathy, mem- had a higher risk of CV events compared understanding of the impact of glomeru-
branous nephropathy (hazard ratio [HR], with the general population (standard- lar disease on CV risk and whether treat-
2.6, 95 percent confidence interval [CI], ized incidence ratio [SIR], 2.46, 95 per- ment may modify this,” she added.

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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
American Society of Nephrology (ASN) Kidney Week 2020 • October 20-25

Metformin may
have CV benefits
in CKD patients
with MetS

AUDREY ABELLA vs those on placebo (p=0.03). [ASN Kid- (p=0.74 and 0.44 for the right and left

M
ney Week 2020, abstract FR-OR20] internal carotid arteries, respectively).
etformin may improve vascular
function in chronic kidney dis- For the secondary outcome, met- Ramos and colleagues used a sam-
ease (CKD) patients with met- formin use compared with placebo led ple of 60 obese/overweight patients
abolic syndrome (MetS), according to to a significant reduction in LAR (p=0.04) (median age 66 years, 80 percent male)
a study presented at ASN Kidney Week and leptin (p=0.003), but not adiponectin with moderate CKD to determine wheth-
2020. (p=0.83), after 16 weeks of treatment. er metformin will improve subclinical CV
disease markers compared with place-
“[Patients with CKD] have unaccept- Insulin resistance is common in pa- bo. Participants were randomized 1:1 to
ably high cardiovascular (CV) mortality tients with CKD and is predictive of CV receive either metformin or placebo for
rate that is not entirely explained by tra- and all-cause mortality in nondiabetic 16 weeks.
ditional CV risk factors. Thus, there is a patients with end-stage renal disease.
current focus on non-traditional risk fac- [Clin J Am Soc Nephrol 2012;7:588- Taken together, the findings suggest
tors in CKD, such as insulin resistance, 594; J Am Soc Nephrol 2002;13:1894- that, apart from its antihyperglycaemic
systemic inflammation, oxidative stress, 1900] “[LAR is] a practical and accurate effect, metformin may also render CV
obesity, and endothelial dysfunction,” index of insulin resistance,” said Ramos, benefits in patients with MetS or predi-
said Dr Everly Ramos from the Vander- adding that a higher LAR ratio is associ- abetes, said Ramos.
bilt University Medical Center, Nashville, ated with higher insulin resistance. [Clin
Tennessee, US, who presented the find- J Am Soc Nephrol 2011;6:767-774] She added that preclinical evidence
ings. When these points are taken together, reflecting the anti-inflammatory effects
the reduced LAR observed in the study of metformin helps elucidate the role
“[Our findings show that] treatment may signal reduced insulin resistance of metformin in the prevention and/
with metformin improved brachial ar- and consequently, a reduced CV risk in or treatment of vascular injury, athero-
tery flow-mediated dilation (FMD) [and] this patient group, she added. sclerosis, and insulin resistance. [Dia-
reduced lectin-adiponectin ratio (LAR),” betes 2015;64:2028-2041; Diabetes
said Ramos. However, metformin use was not 2015;64:1907-1909]
associated with any benefit in the other
After 16 weeks of treatment, there subclinical markers of CV disease such Ramos called for longer and larger
was a significant increase in brachial ar- as aortic pulse wave velocity (p=0.84) trials to ascertain the vascular benefits of
tery FMD among patients on metformin and carotid intima media thickness metformin in this patient setting.

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DOCTOR || DECEMBER ISSUE
 Sponsored Symposium Highlights

Pneumococcal vaccination in at-risk adults:

Assessing targets and benefits
At the recent Pfizer webinar “Pneumococcal Vaccination in High-Risk Individuals: Are We Doing
It Right?”, Dr Petrick Periyasamy, head of the Hospital Canselor Tuanku Muhriz UKM Infectious
Diseases Unit, discussed the currently known epidemiology of adult pneumococcal disease (PD),
as well as the impact of vaccines on PD prevention in at-risk populations.

Dr Petrick Periyasamy
MD (USM), MMed (Int. Med) (UKM) 12% in the early 2000s, with higher mortality rates observed
Consultant in Internal Medicine and among those aged ≥65 years and those with comorbidities.8,9
Infectious Diseases
Hospital Canselor Tuanku Muhriz UKM Vaccine immunogenicity: Targeting key strains
Two vaccine types for PDs exist: plain polysaccharide vaccines
(PVs) and polysaccharide conjugate vaccines (CVs). PVs are
The burden of PD: An overview effective in selected populations but can be limited by poor
Streptococcus pneumoniae is the commonest isolated cause immunologic priming and immune memory induction, and
of community-acquired pneumonia (CAP) globally, underlying low impact on nasopharyngeal carriage.10,11 In CVs, linkage
an estimated 11.9–68.3% of adult PD cases in European between carrier proteins and polysaccharide antigens enables
countries and 29.2% in Asian countries.1,2 In Malaysia, two T-cell-assisted immunological improvements that mitigate most
hospital cohort studies have implicated S. pneumoniae as PV limitations.10
the commonest cause of CAP, based on urinary antigen and
real-time polymerase chain reaction (rt-PCR) testing (8.8% and The 13-valent pneumococcal conjugate vaccine (PCV)
21.7%, respectively).3 covers 13 S. pneumoniae serotypes versus the 23 strains of
the 23-valent pneumococcal polysaccharide vaccine (PPV).11
About 10–30% of pneumococcal pneumonia (PP) cases PPV23 covers almost all PCV13 serotypes except serotype 6A;
present with bacteraemia and are grouped as invasive this point is worth considering as 6A has repeatedly emerged
pneumococcal disease (IPD).1 Local population data on IPD as one of 10 most common pneumococcal isolates from
incidence is limited, although a 2015 study estimated 3.8–8.6 Malaysian paediatric hospital cohorts.11,12,13 In general, PCV13
per 100,000 cases per year in Malaysian children <5 years.4 may provide up to 88.2% coverage of local S. pneumoniae
strains based on recent serotype profiling.13
Risk groups for CAP and IPD
Age is a strong risk factor for CAP and IPD incidence and Can vaccines prevent adult CAP/IPD?
mortality in adults, with substantial increases seen in populations PPV efficacy in preventing PD among the general population is
≥50 years.5 Chronic illnesses (heart and lung conditions, debated; a systematic review of 25 studies from 1966 to 2012
diabetes, alcohol abuse, smoking) and immunocompromising found PPVs generally effective against all-cause pneumonia
conditions also add significant risk (Figure 1).6,7 A risk-stacking in low-income but not high-income countries, with insufficient
effect has been observed with PP and IPD, where each added evidence for routine use in preventing all-cause PD or mortality
comorbidity elevates rates of all-cause pneumonia, PP, and in adults.14 A subsequent 2017 review found PPV23 had a
IPD.7 pooled vaccine efficacy (VE) of up to 64% (95% confidence
interval, CI: 35±80%) by any serotype for PP prevention in the
In Malaysia, reported CAP mortality in small single-centre elderly, although review data was weighted by a 2010 study
cohorts of adults admitted to hospitals ranged from 9.2% to focusing on Japanese nursing home residents.15

Figure 1. Age-related IPD incidence in the US in healthy adults (≥18 years old) versus adults with (A) chronic illnesses and
(B) immunocompromising conditions, 1999–2000.6

A Healthy
Chronic heart disease
B Healthy
Solid cancer
800 Hematological cancer
300 Diabetes HIV/AIDS
Alcohol abuse
Chronic lung disease 700
250
Cases/100,000 persons

Cases/100,000 persons

600
200 500

150 400
300
100
200
50 100

0 0
18-34 35-49 50-64 65-79 ≥80 18-34 35-49 50-64 65-79 ≥80
Age, years Age, years
Incidence rates based on 1999–2000 data on (1) IPD cases in healthy adults (n=1,570) vs adults with ≥1 condition (n=2,765) in a population-based surveillance programme in 7 US
states (n=14.7–15.1 million); and (2) overall demographics of healthy adults (n=50,434) vs adults with ≥1 condition (n=9,597) polled in a national health survey. Combined data was
projected against the 1999-2000 estimated national US population (n=326 million).
Adapted from Kyaw M et al. The Influence of Chronic Illnesses on the Incidence of Invasive Pneumococcal Disease in Adults.6
 Sponsored Symposium Highlights

The CAPiTA trial—a randomized double-blind placebo- against which data the ACIP found routine PCV13 use in adults
controlled trial involving 84,496 adults aged ≥65 years— ≥65 years to have minimal additional impact.19
examined PCV13’s efficacy in preventing first-time vaccine-
type (VT) CAP and IPD over ~4 years post-vaccination (Figure Why aren’t more people vaccinated?
2).16 Over the study period, 139 VT-CAP and 35 VT-IPD first-time Known barriers to pneumococcal immunization include issues
episodes occurred, in which 45.6% VE (95% CI, 21.8–62.5; of disease or vaccine awareness, professional apathy, clashing
p<0.001) was observed for first-time VT-CAP prevention by priorities, and endemic challenges in healthcare delivery
PCV13 versus placebo, as well as 75% VE (95% CI, 41.4–90.8; systems.20 Nevertheless, it is important for physicians to discuss
p<0.001) in first-time VT-IPD prevention.16 pneumococcal vaccination with patients known to have one
or more risk factors for IPD.
In an assessment of 7,254 S. pneumoniae serotypes isolated
from US adults aged ≥18 years with suspected pneumonia
between 2009 and 2017, declines in penicillin and ceftriaxone
nonsusceptibility were observed (72.3% and 73.8%, Key takeaways
respectively), driven mainly by PCV13-type isolates.17 This • S. pneumoniae is the commonest isolated cause of
potential effect of vaccination on S. pneumoniae antimicrobial adult CAP in Europe and Asia.1,2
resistance was correlated with the impact of a US national • Age, chronic medical conditions, behavioural factors,
PCV13 immunization programme since 2010 for children and and immunocompromising conditions substantially
since 2014 for adults aged ≥65 years.17 increase risk of CAP and IPD incidence and severity.5-7
• Stacked risk factors magnify IPD risk, suggesting
potential benefits from targeted pneumococcal
Figure 2. Post-hoc analysis of cumulative episodes of
vaccinations for at-risk populations.7
first-time VT-CAP prevention (primary endpoint) and • Pneumococcal vaccine protection has been
first-time VT-IPD prevention (secondary endpoint).16 demonstrated more effectively for adult IPD prevention
than adult CAP, although PCV13 may confer some
A Vaccine-Type CAP B NB and NI CAP C Vaccine-Type IPD CAP protection among adults aged ≥65 years.16
Placebo • Regardless of prior pneumococcal vaccination status,
90 90 90
% VE, 45.6%; % VE, 45.0%; % VE, 75.0%;
if the use of PPV23 is considered appropriate, PCV13
80 95.2% CI,
21.8–62.5;
80 95.2% CI,
14.2–65.3;
80 95.0% CI,
41.4–90.8;
should be administered beforehand.18
Cumulative No. of Episodes

Cumulative No. of Episodes

Cumulative No. of Episodes

70
p<0.001
70
p<0.007
70
p<0.001 • PCV13 vaccination may play a role in reducing S.
Placebo pneumoniae resistance to antimicrobials.17
60 60 60
PCV13 ACIP, Advisory Committee on Immunization Practices; CAP, community-acquired
50 50 50 pneumonia; CAPiTA, Community-Acquired Pneumonia Immunization Trial in
Adults; CV, conjugate vaccine; IPD, invasive pneumococcal disease; MSIDC,
40 40 40 Malaysian Society of Infectious Diseases and Chemotherapy; PCV, pneumococcal
PCV13 conjugate vaccine; PD, pneumococcal disease; PP, pneumococcal pneumonia;
Placebo PPV, pneumococcal polysaccharide vaccine; PV, polysaccharide vaccine; VE,
30 30 30 vaccine efficacy; VT, vaccine-type.
20 20 20

10 10 10 PCV13
References: 1. Blasi F, et al. Clin Microbiol Infect 2012;18(Suppl 5):7-14. 2. Song J-H, et al. Int
0 0 0 J Antimicrob Agents 2008;31(2):107-114. 3. Mohamed Faisal AH, et al. International Med-
ical Journal Malaysia 2017;16(1):29-36. 4. Maimaiti N, et al. Malaysian Journal of Public
0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 Health Medicine 2015;15(1):25-29. 5. Centers for Disease Control and Prevention. Active
Years since Years since Years since Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus
Vaccination Vaccination Vaccination pneumoniae, 2010. Available at: https://www.cdc.gov/abcs/reports-findings/survreports/
spneu10.pdf. Accessed 5 October 2020. 6. Kyaw MH, et al. J Infect Dis 2005;192(3):377-
PCV13, n=42,240; placebo, n=42,256. Percentage VE values based on per-protocol
analysis data. 386. 7. Shea KM, et al. Open Forum Infect Dis 2014;1:ofu024. doi:10.1093/ofid/ofu024.
8. Hooi LN, et al. Med J Malaysia 2001;56(3):275-284. 9. Loh LC, et al. Respirology
NB, non-bacterial; NI, non-invasive
2004;9:379-386. 10. Harrison LH. Clin Microbiol Rev 2006;19:142-164. 11. Centers for
Adapted from Bonten et al. Polysaccharide Conjugate Vaccine against Pneumococcal Disease Control and Prevention. MMWR Recomm Rep 2010;59:1-18. 12. Rohani MDY,
Pneumonia in Adults.16 et al. Vaccine 2011;29:5688-5693. 13. Arushothy R, et al. Int J Infect Dis 2019;80:129-
133. 14. Moberley S, et al. Cochrane Database Syst Rev 2013;2013(1):CD000422. 15.
Guidelines for vaccine administration Falkenhorst G, et al. PLoS One 2017;12:e0169368. 16. Bonten MJM, et al. N Engl J Med
2015;372:1114-1125. 17. Suaya JA, et al. J Infect 2020;81(4):557-566. 18. Malaysian
In Malaysia, the 2014 Malaysian Society of Infectious Diseases Society of Infectious Diseases and Chemotherapy (MSIDC). Pneumococcal disease. In:
Guidelines for Adult Immunisation. 2nd ed. Kuala Lumpur, Malaysia: MSIDC; 2014:107-113.
and Chemotherapy (MSIDC) guidelines recommend vaccine- 19. Matanock A, et al. MMWR Morb Mortal Wkly Rep 2019;68:1069-1075. 20. Rehm SJ, et
naïve patients with Category A conditions (at highest risk of IPD, al. Postgrad Med 2012;124:71-79.
eg, asplenia or immunocompromised systems) receive PCV13
as an initial dose, followed by PPV23 after 6–12 months.18 A
second PPV23 dose is recommended for all Category A adult
patients 5–10 years after the first PPV23 dose.18 Those with For healthcare professionals only
previous PPV23 vaccinations should receive one PCV13 dose
at least 12 months after their most recent PPV23 dose.18 Sponsored as a service to the medical profession by

By the same guidelines, patients aged ≥60 years or those with Pfizer (Malaysia) Sdn Bhd 197801003134 (40131-T)
at least one Category B condition (at-risk for IPD, eg, chronic Level 10 & 11, Wisma Averis , Tower 2, Avenue 5,
Bangsar South, No. 8, Jalan Kerinchi, 59200 Kuala Lumpur.
cardiac/lung/liver diseases, diabetes, alcoholism, smoking) are Tel: (03) 2281 6000 Fax: (03) 2281 6388
recommended to receive one dose of PCV13.18 www.pfizer.com.my
PP-PRE-MYS-0190-30OCT2020

In the US, the 2019 CDC Advisory Committee on Immunization

Practices (ACIP) guidelines rescinded a recommendation
for routine PCV13 use in healthy and immunocompetent
adults aged ≥65 years, moving to shared clinical decision- Editorial development by MIMS Medica. The opinions expressed in this publication are not
necessarily those of the editor, publisher or sponsor. Any liability or obligation for loss or damage
making based on individual risk of PD and exposure to PCV13 howsoever arising is hereby disclaimed. ©2020 MIMS Medica. All rights reserved. No part of this
serotypes.19 However, this must be considered in the context of publication may be reproduced by any process in any language without the written permission of
the publisher. Enquiries: MIMS Medica Sdn Bhd (891450-U), 2nd Floor, West Wing, Quattro West,
the aforementioned 2010 childhood vaccination programme No. 4, Lorong Persiaran Barat, 46200 Petaling Jaya, Selangor, Malaysia. Tel: (603) 7623 8000 Fax:
(603) 7623 8188 Email: enquiry.my@mims.com
which caused sharp declines in paediatric and adult PD, Website: www.mims.com MY-PFI-472d
 CONFERENCE COVERAGE
Transcatheter Cardiovascular Therapeutics (TCT) Connect 2020 • October 14-18

TCT
Connect 2020
October 14-18

Shorter DAPT okay in high bleeding

risk patients post-PCI
PEARL TOH multinational studies which enrolled HBR

T
patients who had successfully under-
reatment with dual antiplatelet gone PCI using the everolimus-eluting
therapy (DAPT) after PCI* can be XIENCE 90 and 28 stents, respectively.
safely shortened to 1 or 3 months DAPT after PCI comprised aspirin plus a
without raising ischaemic risk in select P2Y12 inhibitor — 3 months for XIENCE
patients with high bleeding risk (HBR**), 90 and 1 month for XIENCE 28 — which
according to the XIENCE 90/28 trials was shorter than the conventional DAPT
presented at TCT 2020. duration. Patients who were event-free
subsequently switched to aspirin mono-
“DAPT is essential for the prevention therapy. [TCT 2020, LB session II]
of ischaemic events after PCI but inevita- Prof Roxana Mehran
bly increases the risk of bleeding, espe- These patients were propensity
cially in patients at HBR, which constitute score-matched and compared against For the powered secondary outcome
up to 40 percent of patients undergoing historical controls drawn from the of BARC type 2–5 bleeding, the rates
the procedure,” said lead investigator all-comer XIENCE V post-approval study were lower with shorter DAPT in both
Professor Roxana Mehran from Icahn (n=8,061). Patients had longer DAPT in XIENCE 90 (5.1 percent vs 7.0 percent;
School of Medicine at Mount Sinai, New XIENCE V, with 90.5 percent of them p= 0.0687 for superiority) and XIENCE
York, New York, US. being on DAPT at 6 months while 85.6 28 (4.9 percent vs 5.9 percent; p=0.19
percent were still on DAPT at 1 year. for superiority) compared with historical
One strategy to avoid bleeding is by rates in XIENCE V, although the differ-
shortening DAPT, Mehran said. “[While] In XIENCE 90, the primary outcome ence did not meet the superiority criteria.
recent trials on next-generation DES*** of all deaths or myocardial infarction
have shown an acceptable safety profile occurred at similar rates as historical However, further restricting the analy-
with a short course of DAPT, the optimal controls (5.4 percent vs 5.4 percent; sis to major bleeding (defined as BARC#
DAPT duration in HBR patients remains p=0.0063 for noninferiority). Similar re- type 3 to 5) showed that major bleeds
unknown.” sults were seen for XIENCE 28, where- were significantly less common with the
by the primary outcome occurred in 3.5 shorter DAPT in both XIENCE 90 (2.2
Positive outcomes percent of patients compared with 4.3 percent vs 6.3 percent) and XIENCE 28
Both XIENCE 90 (n=2047) and 28 percent of historical controls (p=0.0005 (2.2 percent vs 4.5 percent) than the his-
(n=1,605) were prospective, single-arm, for noninferiority). torical cohort — thus meeting the margin

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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
Transcatheter Cardiovascular Therapeutics (TCT) Connect 2020 • October 14-18

for superiority (p<0.0001 and p=0.0156, Not for everyone

respectively). During the presentation, Mehran high-
“[The current data] is only
lighted the extensive list of inclusion and
In addition, the rate of definite/prob- exclusion criteria in patient selection applicable to patients with
able stent thrombosis based on ARC for the study; the latter which involved HBR features, who do
criteria was 0.20 percent in XIENCE 90, STEMI, PCI with overlapping stents, plus not derive a benefit from
which according to Mehran, was signif- various criteria for target lesion.
prolonged DAPT”
icant in comparison against the perfor-
mance goal of 1.2 percent (p<0.0001). Noting the many exclusion crite-
For XIENCE 28, the rate was identical as ria, invited discussant Dr Ziad Ali from
that in historical control, at 0.3 percent. Columbia University Medical Center/ To this, patient selection was again
NewYork-Presbyterian Hospital in New brought to the fore. “[The current data] is
York, New York, US asked what’s left. only applicable to patients with HBR fea-
“The observed treatment tures, who do not derive a benefit from
“I think it’s not for everyone,” said prolonged DAPT and, in fact, shortened
effect applies only to Mehran, who pointed out these studies DAPT is safer,” said XIENCE V co-investi-
patients ‘free’ from adverse looked at more complex patients and gator Professor Marco Valgimigli of Bern
events and adherent to the lesions. “The observed treatment effect University Hospital, Bern, Switzerland.
DAPT regimen in the first 1 applies only to patients ‘free’ from ad-
verse events and adherent to the DAPT “Perhaps in clinical practice, we may
or 3 months post-PCI” regimen in the first 1 or 3 months post- want to use a bleeding risk score to
PCI.” properly risk stratify the patient or the re-
cently proposed HBR criteria,” he added.
Given that XIENCE V was conduct- Also noting that there are previous * PCI: Percutaneous coronary intervention
ed approximately one decade before studies which showed reduced isch- ** at least one risk factor of: age ≥ 75 years, chronic
use of oral anticoagulant, recent major bleeds,
the current XIENCE 90/28 studies, con- aemic events with prolonged DAPT, Ali history of stroke, chronic kidney disease, haemato-
founders related to changes in clinical asked how to reconcile these with the logical disorders, anaemia
*** DES: Drug-eluting stent
practice cannot be excluded, and this current findings. # BARC: The Bleeding Academic Research Consor-
Mehran cited as a study limitation. tium

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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
Transcatheter Cardiovascular Therapeutics (TCT) Connect 2020 • October 14-18

NACMI registry IDs key traits, risks

in patients with COVID-19 and ST-elevation
ROSHINI CLAIRE ANTHONY the MSC groups (median 3 days for

P
both; p<0.001 for both), as was length
atients with ST-elevation and of intensive care unit stay (median 4 vs
COVID-19 have different char- 2 days for COVID-19-positive vs PUI
acteristics than those without groups, respectively; p<0.001).
COVID-19, and may have a higher risk of
in-hospital mortality and stroke, accord- The incidence of in-hospital stroke
ing to initial results of the NACMI* registry was also higher among COVID-19-pos-
study presented at TCT Connect 2020. itive patients compared with the MSC
(3.4 percent vs 0.6 percent; p=0.039) or
The NACMI registry comprised adults PUI groups (2 percent; nonsignificant).
who tested positive or were under inves-
tigation for suspected COVID-19, with “COVID-19-positive patients with
ST-segment elevation or new-onset left ST-elevation represent a unique and
bundle branch block (LBBB) as per 12- high-risk patient population,” said Dr
lead ECG, and clinical signs of myocar- Timothy Henry from The Christ Hospital,
dial ischaemia. Cincinnati, Ohio, US.
(45 for both) vs the MSC group (50).
As of October 4, 2020, the data- I Five previous studies, comprising in
base included 594 patients from 64 nfiltrates on chest X-ray were more total 174 patients, have shown that pa-
sites, of whom 171 were confirmed common in the COVID-19-positive vs tients with COVID-19 who have ST-ele-
COVID-19-positive and 423 who tested PUI group (49 percent vs 17 percent), vation more frequently present in hos-
negative following investigation (PUI). as was dyspnoea (58 percent vs 38 per- pital, have more thrombotic lesions and
They were compared with a historical cent), while chest pain was less common more frequently without a culprit, and are
comparator group comprising a propen- (53 percent vs 78 percent; p<0.001 for at a higher mortality risk. Furthermore,
sity-matched cohort of patients from the all). there is considerable controversy re-
Midwest STEMI Consortium (MSC). garding the appropriate management of
Twenty-one percent of COVID-19- these patients, said Henry.
There were no significant differences positive patients did not undergo an-
in age or sex between the groups, though giography compared with 5 percent in The present analysis showed that
there were significant differences in eth- the PUI group (p<0.001) and 0 in the primary PCI is preferable and feasible
nicity. The COVID-19-positive group had MSC group. Primary PCI rates were 71, in COVID-19-positive patients with D2B
more patients with diabetes than the PUI 80, and 81 percent, respectively, while times similar to PUI or COVID-19-nega-
(44 percent vs 33 percent; p=0.015) and thrombolytics were given in 6, 2, and 3 tive patients. This supports the current
MSC groups (20 percent; p<0.001). [TCT percent, respectively. Door-to-balloon COVID-19-specific STEMI guidelines
Connect 2020, Late-Breaking Clinical (D2B) time was also comparable be- produced by SCAI/ACC/AHA***, he said.
Science Session I] tween groups (median 80, 78, and 86
minutes, respectively). Henry noted that the mortality rate
Pre-PCI** cardiac arrest incidence was only about 12–13 percent among
was comparable across groups (12, 17, In-hospital mortality was significantly those who underwent PCI but was high-
and 11 percent of the COVID-19-posi- higher among COVID-19-positive pa- er among patients who did not undergo
tive, PUI, and MSC groups, respectively). tients compared with PUI (32 percent vs angiography, though these are early re-
However, cardiogenic shock was more 12 percent) or the MSC cohort (6 per- sults and more research is warranted.
common in the COVID-19-positive vs cent; p<0.001 for both).
* NACMI: North American COVID-19 ST-Segment
PUI group (20 percent vs 14 percent; Elevation Myocardial Infarction
p=0.074) or MSC group (5 percent; Duration of hospitalization was also ** PCI: Percutaneous coronary intervention
*** SCAI: Society for Cardiovascular Angiography & In-
p<0.001). Ejection fraction was lower in longer in the COVID-19-positive (medi- terventions; ACC: American College of Cardiology;
the COVID-19-positive and PUI groups an 6 days) compared with the PUI and AHA: American Heart Association

38
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
Transcatheter Cardiovascular Therapeutics (TCT) Connect 2020 • October 14-18

Crushed prasugrel offers no reperfusion

benefit prior to PCI
ELVIRA MANZANO percent vs 57.3 percent; p=0.55). There hospitalization and at 30 days. Definite

G
were also no differences between the stent thrombosis occurred in one patient
iving crushed prasugrel to pa- groups in partial (30–70 percent), mini- in the crushed group and two patients in
tients with ST-segment elevation mal (<30 percent), or >50 percent res- the integral group.
myocardial infarction (STEMI) en olution. [Circulation 2020;doi:10.1161/
route to the hospital for planned PCI* CIRCULATIONAHA.120.051532] In exploratory analysis, the coprimary
does not improve reperfusion rates com- “These findings hold in spite of the endpoint results were consistent across
pared with giving the tablets whole in the fact that crushed tablets of prasugrel multiple subgroups, although there was
COMPARE CRUSH trial. led to more potent platelet inhibition vs a trend toward greater benefit on TIMI 3
integral tablets,” said study author Dr flow in the crushed tablet group in pa-
The finding was a stark contrast to ob- Georgios Vlachojannis from the Univer- tients older than age 75 years (pfor interac-
servations that early dosing with crushed sity Medical Center Utrecht, the Neth- tion
=0 .04), and those presenting with an-
pills improved platelet inhibition over in- erlands during his presentation at TCT terior infarction (pfor interaction = 0.03), or with
tegral tablet ingestion. [J Am Coll Cardiol 2020. “Whether faster and more potent a history of prior PCI (pfor interaction <0.01).
2016; 3;67:1994-2004; https://clinicaltri- antiplatelet therapy can improve coro-
als.gov/ct2/show/NCT01992523] nary reperfusion in contemporary STEMI “Nevertheless, these results should
treatment regimen warrants further in- be regarded as hypothesis-generating,”
While COMPARE CRUSH did show vestigation.” the authors said. “Opioids use in the am-
an enhanced degree of platelet inhibition bulance was remarkably low in our study
in the group receiving crushed prasugrel, To crush or not: vs that in the ATLANTIC trial, which might
the benefits did not translate to reperfu- It doesn’t matter explain why we did not observe any sig-
sion effects. The study enrolled 727 patients (mean nificant interaction.”
age 62 years, 23 percent female) with
At pre-PCI angiography, patients suspected STEMI and symptom onset “What we know with COMPARE
treated with crushed prasugrel or whole within 6 hours. They were randomized to CRUSH, and this is important, is that we
prasugrel had similar rates of the copri- a 60 mg loading dose of crushed pras- tried to give the medication as soon as
mary endpoints of TIMI 3** flow in the ugrel or whole prasugrel in addition to possible and tried to give this in a for-
infarct-related artery (31 percent vs 32.7 500 mg of intravenous aspirin and 5,000 mulation which has the most favourable
percent; p=0.64) and complete ST-seg- units of intravenous heparin in the am- pharmacodynamics profile, and we still
ment resolution at 1 hour post-PCI (59.9 bulance. see it’s not doing the job,” Vlachojannis
said.
In terms of the pri-
mary safety endpoint of On questions whether treatment time
TIMI major and BARC may have played a role in teasing out the
type 3 or higher bleed- relatively modest differences that platelet
ing within 48 hours reactivity may have on clinical outcomes,
post treatment, there Vlachojannis said the short time intervals
was no difference ob- to medical contact have certainly influ-
served between the enced the outcomes.
crushed and integral
groups (0.4 percent vs The findings underscore the need for
0.7 percent). alternative strategies to achieve faster
and more potential platelet inhibition in
Death, MI, stroke, patients undergoing primary PCI, said
and urgent revascular- Vlachojannis.
ization rates were also
comparable between * PCI: primary percutaneous coronary intervention
groups during index ** TIMI 3: thrombolysis in myocardial infarction 3

39
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
Transcatheter Cardiovascular Therapeutics (TCT) Connect 2020 • October 14-18

VOYAGER PAD:
No mortality risk/benefit with paclitaxel-coated
devices in lower extremity revascularization
ROSHINI CLAIRE ANTHONY from the University of Colorado School of

T
Medicine, Aurora, Colorado, US, at TCT
he use of paclitaxel paclitaxel-coat- Connect 2020.
ed devices did not appear to af-
fect mortality risk in patients with Its success, however, is limited by
symptomatic peripheral artery disease restenosis, with paclitaxel-coated de-
(PAD) who underwent endovascular low- vices introduced to attenuate restenosis
er extremity revascularization, according risk and improve patency.
to subgroup analysis of the VOYAGER
PAD* trial. Previous research on mortality risk
associated with paclitaxel-coated device
In the trial, 6,564 patients with symp- use has been inconclusive, with some
tomatic lower extremity PAD who had studies suggesting an increased risk, [J
undergone revascularization were ran- Am Heart Assoc 2018;7:e011245; Circu-
domized 1:1 to receive rivaroxaban (2.5 lation 2020;141:1859-1869] and others
mg BID) or placebo, in addition to aspirin demonstrating no mortality risk. [Cathe-
(100 mg/day). tween the drug-coated and non-drug- ter Cardiovasc Interv 2020;doi:10.1002/
coated device groups (12.1 percent vs ccd.29152; Eur Heart J 2020;41:3732-
Previously published results showed 12.6 percent; HR, 0.95, 95 percent con- 3739]
a significantly reduced risk of the pri- fidence interval [CI], 0.83–1.09; p=0.49).
mary endpoint (acute limb ischaemia, The deaths were primarily due to cardio- “[In this analysis,] IPTW** success-
major amputation for vascular causes, vascular causes (54 and 62 percent of fully adjusted for known confounders
myocardial infarction, ischaemic stroke, deaths in the drug-coated and non-drug- and showed no mortality risk or benefit
and cardiovascular death) with rivarox- coated device groups, respectively). associated with drug-coated devices,
aban vs placebo (3-year incidence: 17.3 including in subgroups by device type,”
percent vs 19.9 percent; hazard ratio The findings were consistent regard- said Hess.
[HR], 0.85; p=0.0085). [N Engl J Med less of device type, namely comparisons
2020;382:1994-2004] between using drug-coated balloon and “This analysis from VOYAGER PAD
percutaneous transluminal angioplas- addresses many of the limitations of cur-
The present analysis assessed if the ty (HR, 0.99, 95 percent CI, 0.82–1.20) rently available data regarding mortality
primary outcome was consistent regard- or between drug-eluting stent and bare and paclitaxel and adds to the literature
less of use of paclitaxel-coated devices metal stent (HR, 1.04, 95 percent CI, examining the safety of drug-coated de-
and included 4,379 patients who under- 0.84–1.28). vices,” she continued.
went endovascular index lower extremity
revascularization. Of these, 31 percent The reduced risk of the primary end- “[In addition,] the benefit of rivarox-
were treated with a drug-coated device, point with rivaroxaban vs placebo also aban 2.5 mg twice daily with aspirin vs
of whom 78, 17, and 5 percent received did not differ with device type (HR, 0.87, aspirin alone on reducing ischaemic limb
drug-coated balloon, drug-coated stent, 95 percent CI, 0.65–1.15 for drug-coat- and cardiovascular outcomes after re-
and both, respectively. The patients were ed device and HR, 0.89, 95 percent CI, vascularization for symptomatic PAD is
followed up for a median 31 months. 0.74–1.07 for non-drug-coated device; consistent regardless of drug-coated de-
[TCT Connect 2020, Endovascular 1: pinteraction=0.88). vice use,” she said.
Late-Breaking Clinical Trials and Science]
* VOYAGER PAD: Efficacy and safety of rivaroxaban
“Endovascular revascularization is in reducing the risk of major thrombotic vascular
In weighted analysis comprising indicated for improvement of symptoms events in subjects with symptomatic peripheral
artery disease undergoing peripheral revasculariza-
4,316 patients, 394 deaths occurred. and limb salvage in symptomatic PAD,” tion procedures of the lower extremities
All-cause mortality was comparable be- said Associate Professor Connie Hess ** IPTW: Inverse Probability Treatment Weighting

40
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DOCTOR || DECEMBER ISSUE
 Sponsored Symposium Highlights

Confronting the everchanging epidemiology

of IMD: The value of meningococcal
vaccination in the paediatric population
At the Nimenrix Speaker Training Workshop webinar, Dr Amgad Gamil of Pfizer Inc.
discussed updates on the epidemiology of invasive meningococcal disease (IMD), while
simultaneously reviewing the latest immunogenicity and safety data of the MenACWY-TT
vaccine (Nimenrix®, Pfizer) in the paediatric population.

Dr Amgad Gamil Burden of IMD in Malaysia13–15

Senior Director of Emerging Markets Epidemiological data on the burden of IMD is understudied
Regional Medical Lead for Africa, in the Southeast Asia region.12 A single-centre, 5-year
Middle East & Asia regions retrospective study showed that N. meningitidis accounted
Pfizer Inc.
for about 4% of bacterial meningitis cases.13 Notably,
another single-centre, retrospective study that included
12 cases of laboratory-confirmed IMD (aged 10–64 years)
revealed a high mortality rate of 25%.14 Separately, a
IMD is a significant global public health prevalence study of N. meningitidis carriage among
concern1 asymptomatic military recruits aged 17–24 years showed
IMD is a major cause of meningitis and septicaemia a high carriage rate of 37%.15 The rate is slightly higher than
globally.2 A result of Neisseria meningitidis, IMD is known the carriage rate observed in the general population,6
for its rapid onset and poor outcomes, with the case but lower compared with other studies among military
fatality rate reaching up to 50% in untreated cases.3 recruits.15
Even with appropriate treatment, approximately 10% of
patients die within 24–48 hours of symptom onset, and Global practices and the impact of
up to 10–20% of IMD survivors suffer from severe life-long vaccination on IMD burden16–19
disabling complications, such as mental retardation and
neurological dysfunction.2 Additionally, IMD can result Vaccination is the most effective measure in preventing
in a substantial economic burden, with an estimated IMD.16,17 The introduction of a monovalent MenC conjugate
lifetime societal cost of USD319,896.74 (including a direct vaccine in England and Wales in 1999 led to a significant
healthcare cost of US$65,035.49) per IMD case.4 93% reduction in the incidence of serogroup C IMD across all
age groups.18 A similar trend was also observed when MenA
vaccination campaign was introduced in nine countries
Who is at risk of IMD?5 within the African meningitis belt in 2010. In this study, the
IMD can affect individuals of all ages, but the incidence of incidence of confirmed serogroup A IMD was reduced
IMD is the highest in children aged <1 year, with a second by more than 99% in the fully vaccinated population.19
peak occurring in adolescence.5 A meta-analysis showed Nevertheless, monovalent meningococcal conjugate
that the prevalence of meningococcal carriage increased vaccines (MCVs) are only effective in controlling disease
from 4.5% in infants to 23.7% in 19-year olds.6 Infants are due to a single serogroup and lack the broad coverage
particularly vulnerable to IMD because of their immature needed to reduce the overall incidence of IMD.16,17
immune system and the waning of protective maternal
antibodies after birth.7 Meanwhile, the higher risk for IMD Vaccination with MenACWY-TT protects
in adolescents and young adults may be attributed to
increased social mixing behaviours, such as living in close infants and young children against IMD
quarters and smoking.1,8 Other risk factors associated with caused by serogroups A, C, W-135 and Y23,24
increased risk for contracting IMD include close contact Recently, epidemics due to serogroups W-135 and Y
with a case, attending large gatherings (eg, Umrah and are becoming more common, 10,20–22 leading to the
Hajj), compromised immune system (eg, anatomical or development of tetravalent MCVs to protect against
functional asplenia), and travelling to endemic areas in serogroups A, C, W-135 and Y. A phase III, randomised
the meningitis belt of sub-Saharan Africa.5,9 controlled trial (RCT) showed that coadministration of
two or three primary doses of MenACWY-TT with routine
IMD epidemiology is unpredictable childhood vaccines induced protective antibody responses to
and varies substantially with time and serogroups A, C, W-135 and Y in infants aged 6–12 weeks.
Furthermore, a booster dose of MenACWY-TT administered
geographical location1 in the second year of life resulted in a robust memory
There are 12 recognised serogroups of N. meningitidis, response to the four serogroups.23 Similarly, another phase
six of which (A, B, C, W-135, X and Y) cause nearly III RCT showed that MenACWY-TT could protect children
all IMD cases. Furthermore, meningococci of these aged 2–10 years against IMD caused by serogroups A,
serogroups can cause both endemic disease and C, W-135 and Y.24 In both trials, immune responses to
outbreaks.2 Nonetheless, the epidemiology of IMD is serogroup C induced by MenACWY-TT were noninferior to
constantly evolving,10,11 underscoring the need for active that induced by monovalent MenC vaccines.23,24
surveillance and monitoring. For instance, serogroup A
was predominant in Africa and Europe from the start to MenACWY-TT can be coadministered with
mid-20th century. Since 1970s, nearly 90% of IMD has been
attributed to serogroups A, B and C globally. In recent routine paediatric vaccines23–25
years, there has been a noticeable increase in IMD MenACWY-TT has been shown to elicit immune responses
incidence due to subgroups W-135 and Y in numerous against the four aforementioned meningococcal
countries, particularly among adults and the elderly.10 serogroups, regardless of the primary vaccination
 Sponsored Symposium Highlights

schedules.25 Moreover, coadministration of MenACWY-TT Recommendations on meningococcal

with routine paediatric vaccines (eg, DTPa-HBV-IPV/ vaccination2,30
Hib, DTPa-IPV/Hib and PHiD-CV) during the first years The World Health Organisation recommends countries with
of life was immunogenic and well tolerated.23,25 These high or intermediate endemic rates of IMD and countries
trials support the potential use of MenACWY-TT in routine with frequent epidemics to introduce appropriate
paediatric vaccination programme to protect infants and large-scale meningococcal vaccination programmes.
young children against IMD caused by the A, C, W-135 Meanwhile, in countries where IMD occurs less frequently,
and Y meningococcal serogroups.16 meningococcal vaccination is recommended for defined
risk groups, such as children and young adults residing in
MenACWY-TT elicits a persistent immune closed communities.2 In response to this, the Malaysian
response for up to 10 years post-vaccination26,27 Society of Infectious Diseases and Chemotherapy
A single dose of MenACWY-TT can offer long-term protection recommends vaccinating target populations, including
against the A, C, W-135 and Y meningococcal serogroups. pilgrims attending the Hajj or Umrah, travellers to epidemics
Two phase IIIb studies demonstrated that functional regions and adults with high-risk medical conditions.30
antibody responses persisted for up to 10 years after primary
vaccination with a single dose MenACWY-TT among Key takeaways
children aged 1–10 years26 and adolescents aged 11–17 years.27
Similarly, long-term antibody persistence to a single ● IMD occurs most frequently in infants and adolescents.3
MenACWY-TT primary dose was also observed in individuals ● MenACWY-TT elicits a protective antibody response
aged 11–55 years.28 against all four meningococcal serogroups (A, C,
W-135 and Y), following vaccination in infants and
The safety and immunogenicity of MenACWY-TT children aged ≥6 weeks to ≤10 years.23,25
has been evaluated across all age groups16 ● MenACWY-TT can be administered concomitantly
MenACWY-TT is the only tetravalent MCV that can be with common routine paediatric vaccines.23–25
administered in individuals aged ≥6 weeks, with no upper
age limit.16,29 ● MenACWY-TT is the only tetravalent MCV that can
be administered in all age groups.16,29
Infants Toddlers Children ● MenACWY-TT induces persistent immune responses
6 weeks to <6 months 12–23 months 2–10 years
of up to 10 years post-primary series in infants,
● Two doses, with the first ● Immunogenicity is ● Immunogenicity is
dose given from 6 weeks of comparable with noninferior to MenACWY-PS children, adolescents and adults.26–28
age, with an interval of MenC-CRM and MenC-CRM
2 months between doses. ● Can be coadministered
● A booster dose is given at with MMR, MMRV, DTaP-
approximately 12 months HBV-IPV/Hib, PCV10 and References: 1. Martinón-Torres F. J Adolesc Heal 2016;59:S12–S20. 2. World Health Organisation.
of age PCV13 Wkly Epidemiol Rec 2011;86:521–539. 3. World Health Organisation. Meningococcal meningitis: Key
● Immunogenicity was non- facts. Available at: https://www.who.int/news-room/fact-sheets/detail/meningococcal-meningitis.
inferior to MenC-CRM and Accessed 23 November 2020. 4. Wang B, et al. Vaccine 2019;37:6885–6893. 5. Centres for Diseases
MenC-TT Control and Prevention. Meningococcal disease: Technical and clinical information. Available at:
https://www.cdc.gov/meningococcal/clinical-info.html. Accessed 22 September 2020. 6. Christensen
Adolescents Adults Elderly H, et al. Lancet Infect Dis 2010;10:853–861. 7. Stephens DS, et al. Lancet 2007 30;369:2196–2210.
11–17 years 18–55 years ≥56 years 8. Spyromitrou-Xioufi P, et al. Eur J Pediatr 2020;179:1017–1027. 9. Memish ZA, et al. J Infect Public
Health 2010;3:143–151. 10. Abio A, et al. Pathog Glob Health 2013;107:373–380. 11. Halperin SA, et al.
● Immunogenicity is ● Immunogenicity is ● Demonstrated Vaccine 2012;30 (Suppl 2):B26–B36. 12. Jafri RZ, et al. Popul Health Metr 2013;11:12. 13. Erleena Nur H,
noninferior to MenACWY-PS noninferior to MenACWY-PS immunogenicity against et al. Southeast Asian J Trop Med Public Heal 2008;39:73–77. 14. Raja N, et al. J Postgr Med 2006;52:23–
● Can be coadministered four meningococcal 29. 15. Rohani M, et al. Malays J Pathol 2007;29:91–94. 16. Presa J, et al. Infect Dis Ther 2019;8:307–333.
with HPV bivalent and serogroups 17. McCarthy PC, et al. Vaccines (Basel) 2018;6:12. 18. Gray SJ, et al. J Med Microbiol 2006;55:887–
recombinant vaccine in
individuals aged 9–25 years 896. 19. Trotter CL, et al. Lancet Infect Dis 2017;17:867–872. 20. Taha MK, et al. Lancet 2000;356:2159.
21. Decosas J, Koama JBT. Lancet Infect Dis 2002;2:763–765. 22. Rosenstein NE, et al. J Infect Dis
1999;180:1894–1901. 23. Merino Arribas JM, et al. Pediatr Infect Dis J 2017;36:e98–e107. 24. Knuf M,
CRM, cross-reacting material of diphtheria toxin; DTaP, diphtheria-tetanus-acellular et al. Eur J Pediatr 2013;172:601–612. 25. Dbaibo G, et al. Vaccine 2018;36:4102–4111. 26. Vesikari T,
pertussis; HAV, hepatitis A virus; HBV, hepatitis B virus; Hib: Haemophilus influenzae type et al. Hum Vaccin Immunother 2020;16:1280–1291. 27. Quiambao B, et al. Hum Vaccin Immunother
b; HPV, human papillomavirus; IPV, inactivated polio vaccine; MMR, measles–mumps– 2020;16:1272–1279. 28. Borja-Tabora CFC et al. BMC Infect Dis 2020;20:426. 29. Nimenrix® (Meningococcal
rubella; MMRV, measles–mumps–rubella–varicella; PCV10, 10-valent pneumococcal groups A, C, W-135 and Y conjugate vaccine) [full prescribing information]. 23 September 2020.
conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; 30. Malaysian Society of Infectious Diseases and Chemotherapy. Guidelines for adult immunisation,
PS, polysaccharide; TT, tetanus toxoid 2nd edition; 2014.

ABBREVIATED PRODUCT INFORMATION NIMENRIX1

CONTENTS: Meningococcal polysaccharide serogroups A, C, W-135 and Y conjugate vaccine. PRESENTATION: Vaccine (inj) [vial (white powder for inj) & pre-filled syringe (clear, colorless soln for inj)] 5 mcg/0.5
mL x 1's. DESCRIPTION: Each 0.5 mL of the reconstituted Nimenrix (1 dose) contains Neisseria meningitidis polysaccharide serogroups A, C, W-135 and Y 5 mcg (conjugated to tetanus toxoid carrier protein
44 mcg). It also contains the following excipients: Powder: Sucrose and trometamol. Solvent: Sodium chloride and water for injection. INDICATIONS/USES: Active immunisation of individuals from 6 weeks of
age against invasive meningococcal diseases caused by Neisseria meningitidis serogroups A, C, W-135 and Y. DOSAGE & ADMINISTRATION: Primary immunisation: Infants from 6 weeks to less than 6 months
of age: Two doses, each of 0.5ml, with the first dose given from 6 weeks of age, with an interval of 2 months between doses. Unvaccinated infants from 6 months to less than 12 months of age: One dose of
0.5ml given from 6 months of age. Children from 12 months of age: One dose of 0.5ml. Booster vaccination: After completion of the primary immunisation course in infants from 6 weeks to less than 6 months of
age, a booster dose should be given at 12 months of age. In previously vaccinated infants from 6 months to less than 12 months of age, a booster dose should be given at 12 months of age with a minimum
interval of at least 2 months after the primary dose. For children from 12 months of age, booster dose is not routinely administered, however may be given in some situations. Nimenrix may be given as a
booster dose to individuals who have previously received primary vaccination with Nimenrix or other conjugated or plain polysaccharide meningococcal vaccines. Nimenrix should be used in accordance
with available official recommendations. Administration: For IM injection only. The injection sites are the anterolateral aspect of the thigh in infants or the anterolateral aspect of the thigh or deltoid muscle in
individuals from 1 year of age. CONTRAINDICATIONS: Hypersensitivity to meningococcal polysaccharide serogroups A, C, W-135 and Y or to any of the excipients of Nimenrix. WARNING and PRECAUTIONS:
Nimenrix should under no circumstances be administered intravascularly, intradermally or subcutaneously. It is a good clinical practice to precede vaccination by a review of the medical history (especially
with regard to previous vaccination and possible occurrence of undesirable effects) and a clinical examination. As with all injectable vaccines, appropriate medical treatment and supervision should always
be readily available in case of a rare anaphylactic event following the administration of Nimenrix. As with other vaccines, vaccination with Nimenrix should be postponed in patients suffering from an acute
severe febrile illness. The presence of a minor infection e.g., cold, should not result in the deferral of vaccination. Syncope (fainting) can occur following or even before, any vaccination as a psychogenic
response to the needle injection. It is important that procedures are in place to avoid injury from faints. As with other vaccines administered IM, Nimenrix should be given with caution to individuals with
thrombocytopenia or any coagulation disorder since bleeding may occur following an IM administration to these subjects. Nimenrix will only confer protection against Neisseria meningitidis serogroups A, C,
W-135 and Y. The vaccine will not protect against other N. meningitidis serogroups. As with any vaccine, a protective immune response may not be elicited in all vaccines. It may be expected that in patients
receiving immunosuppressive treatment or patients with immunodeficiency, an adequate immune response may not be elicited. Persons with certain complement deficiencies and persons receiving treatment
that inhibit terminal complement activation (for example, eculizumab) are at increased risk for invasive disease caused by Meningococcal polysaccharide serogroups A,C,W-135 and Y even if they develop
antibodies following vaccination with Nimenrix. Safety and immunogenicity data are available for a limited number of individuals with increased susceptibility to meningococcal infection due to anatomic or
functional asplenia (such as sickle cell disease). A single-dose administered at 6 months was associated with lower human complement serum bactericidal assay (hSBA) titres to groups W-135 and Y compared
with three doses administered at 2, 4 and 6 months. If an individual aged 6 months and above is expected to be at immediate risk of invasive meningococcal disease due to the exposure to groups W-135
and Y, consideration may be given to administering a second primary dose after an interval of 2 months. Persistence of antibodies has been evaluated up to 5 years after vaccination. The persistence studies
have shown a waning of serum bactericidal antibody titres against MenA when using human complement in the assay (hSBA). In individuals expected to be at particular risk of exposure to MenA and received
a dose of Nimenrix more than approximately one year previously, consideration may be given to administering a booster dose. A booster dose might be considered in individuals remaining at high risk of
exposure to meningococcal disease cause by groups A,C,W-135 and Y. Currently, there is very limited information available on the safety of a booster dose of Nimenrix. Although Nimenrix contains tetanus
toxoid, this vaccine does not substitute for tetanus immunisation. If Nimenrix is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection
sites. Nimenrix should be used during pregnancy only when clearly needed, and the possible advantages outweigh the potential risks for the foetus. Nimenrix should only be used during breast-feeding when
the possible advantages outweigh the potential risks. ADVERSE REACTIONS: The safety profile presented as follows is based on a pooled analysis in more than 9,000 subjects from the age of 1 year on, who
have been vaccinated with 1 dose of Nimenrix in clinical studies. The very common and common adverse events are: Metabolism and Nutrition Disorders: Very Common: Loss of appetite. Psychiatric Disorder:
Very Common: Irritability. Nervous System Disorder: Very Common: Drowsiness, headache. Gastrointestinal Disorder: Common: Gastrointestinal symptoms (including diarrheoa, vomiting and nausea). General
Disorders and Administration Site Conditions: Very Common: Fever, swelling, pain and redness at injection site, fatigue. Common: Injection site haematoma. API-NIMENRIX-0920
Reference document: 1. Nimenrix Prescribing Information (Malaysia) dated 23 September 2020.

For healthcare professionals only

Sponsored as a service to the medical profession by

Pfizer (Malaysia) Sdn Bhd 197801003134 (40131-T) Editorial development by MIMS Medica. The opinions expressed in this publication are not
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 CONFERENCE COVERAGE
HIV Glasgow 2020 Virtual Meeting • October 5-8

HIV Glasgow
2020
October 5-8

BICSTaR: Starting or switching to B/F/TAF

beneficial for PLHIV
ROSHINI CLAIRE ANTHONY treatment-experienced patients (n=357) The only two serious DRAEs were

S
who switched to the regimen. [HIV in treatment-experienced patients (two
tarting or switching to the sin- Glasgow 2020, abstract P046] cases of depression). At 12 months, treat-
gle-tablet regimen of bictegravir/ ment-naïve (n=48) and treatment-experi-
emtricitabine/tenofovir alafenam- Effectiveness was consistent regard- enced (n=269) patients experienced a
ide (TAF) led to low HIV-1 RNA viral load less of age (≥50 or <50 years) in both median weight change of +2.5 and +0.9
in people living with HIV (PLHIV), accord- treatment-naïve (100 percent for both kg, respectively, while BMI changes were
ing to the BICSTaR study presented at age categories) and treatment-experi- +0.8 and +0.3 kg/m2, respectively. Nine-
HIV Glasgow 2020. enced patients (93 percent [≥50 years] teen and 5 percent of treatment-naïve
and 98 percent [<50 years]), or sex (100 and treatment-experienced patients, re-
The findings were based on analy- percent of both male and female treat- spectively, experienced a weight gain of
sis of 513 PLHIV (91 percent male, 89 ment-naïve patients and 96 and 97 per- >10 percent.
percent White) from Europe and Can- cent of male and female treatment-expe-
ada who had completed 12 months of rienced patients, respectively). There were no major resistance sub-
follow-up in the ongoing BICSTaR study. stitutions to the components of the bicte-
Most patients were treatment experi- gravir/emtricitabine/TAF regimen.
enced (ie, prior exposure to antiretroviral “Effectiveness was
therapy [ART]; n=429, median age 49 “[The results of the BICSTaR study
consistent regardless
years), while the remaining 84 patients show that] the use of bictegravir/em-
(median age 38 years) were treatment of age or sex” tricitabine/TAF in this real-world clinical
naïve. cohort was associated with a high level
of effectiveness and safety through 12
In the treatment-experienced cohort, Fourteen and 15 percent of treat- months, inclusive of male, female, and
71, 18, and 13 percent switched from ment-naïve and treatment-experienced older PLHIV,” said the researchers.
INSTI-, NNRTI-, and PI-*based regimens, patients experienced drug-related ad-
respectively, with 26 percent having prior verse events (DRAEs), the most frequent Successful switch from
exposure to tenofovir disoproxil fumarate being gastrointestinal and neuropsychi- PI-based regimen
(TDF). Eight percent had previously ex- atric AEs (5 and 4 percent, respectively). Another study also showed sustained
perienced virological failure. Ninety percent of participants remained virological suppression among most
on treatment; DRAE-related discontinu- PLHIV who switched from a PI-based
At 12 months, all treatment-naïve ations occurred in 3.6 and 7.2 percent regimen to bictegravir/emtricitabine/TAF.
patients who initiated bictegravir/emtric- of treatment-naïve and treatment-experi-
itabine/TAF (n=74) achieved a viral load enced patients, respectively. Participants were 577 patients with
of <50 copies/mL, as did 96 percent of virologically-suppressed HIV (HIV-1 RNA

44
54
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 CONFERENCE COVERAGE
HIV Glasgow 2020 Virtual Meeting • October 5-8

<50 copies/mL) who were on a boost-

ed PI-based regimen of atazanavir or
darunavir plus either emtricitabine/TDF There was no documented incidence Body weight changed by a median 2
or abacavir/lamivudine for ≥6 months of resistance to bictegravir/emtricitabine/ kg at weeks 48 and 72, and 2.2 kg at
pre-screening. They were randomized TAF or discontinuation due to lack of effi- week 96. Change in the total:HDL cho-
1:1 to either remain on their baseline PI cacy during the open-label phase. lesterol ratio was -0.1, -0.2, and -0.2
regimen or switch to bictegravir/emtric- at weeks 48, 72, and 96, respectively.
itabine/TAF. About 14 percent of patients on LDL-cholesterol changed by a medi-
bictegravir/emtricitabine/TAF experi- an -3, -4, and -7 mg/dL, respectively,
Following 48 weeks of the random- enced DRAEs which were mostly grade and estimated glomerular filtration rate
ized treatments, 516 patients (medi- 1, the most common being headache (2 changed by a median -4.2, -6.3, and
an age 48 years, 17 percent female, percent). AEs led to discontinuation in -3.4 mL/min.
26 percent Black) were enrolled in the six patients; four during the open-label
open-label extension study and received phase. “Long-term follow-up of … switch-
bictegravir/emtricitabine/TAF, 272 and ing to bictegravir/emtricitabine/TAF from
244 who were originally randomized to a boosted PI regimen demonstrates
bictegravir/emtricitabine/TAF and the PI “Switching to continued high rates of virologic sup-
regimen, respectively. Patients received bictegravir/ pression with no emergent resistance
bictegravir/emtricitabine/TAF for a medi- and was safe and well tolerated through
an 101 weeks.
emtricitabine/TAF from a maximum of 156 weeks,” noted the re-
a boosted PI regimen searchers.
Virological suppression (HIV-1 RNA demonstrates continued
<50 copies/mL) during the open-label high rates of virologic
phase was maintained in 97–100 per-
cent of patients at all timepoints over
suppression with no
156 weeks. [HIV Glasgow 2020, abstract emergent resistance” * INSTI: Integrase strand transfer inhibitor; NNRTI:
Non-nucleoside reverse transcriptase inhibitor; PI:
P036] Protease inhibitor

45
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
HIV Glasgow 2020 Virtual Meeting • October 5-8

Switching to B/F/TAF maintains high viral

suppression in elderly with HIV
PEARL TOH were on E/C/F/TAF (92 percent) at base- four AEs leading to premature discontin-

S
line. [HIV Glasgow 2020, abstract P038] uation of study drug: one due to a grade
witching to a single-tablet regi- 2 abdominal discomfort which was con-
men of bictegravir/emtricitabine/ At 72 weeks after switching, eighty sidered to be drug-related, another due
tenofovir alafenamide (B/F/TAF) participants (93 percent) continued to to alcohol withdrawal, one because of
maintains virologic suppression over 72 maintain high rates of virologic sup- benzodiazepine withdrawal, and the
weeks in older people living with HIV pression. The remaining six participants fourth was suicide. Grade 3–4 drug-re-
(PLWH), according to a study presented (7 percent) did not have virologic data lated AEs occurred in 2 percent of the
at HIV Glasgow 2020. within the study window, of which four participants, but there were no serious
were due to treatment discontinuation. AEs deemed to be drug-related.
“As the age of PLWH increases, Even so, the last available HIV-1 RNA
studies are needed to assess the safe- was <50 copies/mL for the four who For laboratory-related AEs, seven re-
ty and efficacy of antiretroviral therapy had discontinued due to adverse events ported were of grade 3 and one was of
[ART] in this population. Older individu- (AEs). grade 4, the latter being hyperkalaemia.
als are at increased risk of comorbidi- There were no discontinuations due to
ties and polypharmacy, so ensuring the After excluding those with no data bone, renal or hepatic AEs.
safety and tolerability of ART in older available, the rate of virologic suppres-
PLWH is critical,” said the researchers. sion was 100 percent at week 72 in “Through week 72, high rates of vi-
missing-data imputation analysis. The rologic suppression were maintained in
CD4 cell count changed by a median of PLWH who switched to B/F/TAF,” the
“Through week 72, 53 cells/mm3 (interquartile range, −49 to researchers concluded.
high rates of virologic 120) from baseline. No virologic failures
were reported after switching, nor was “The safety and efficacy data sup-
suppression were
there any emergent resistance. port the switch to B/F/TAF in virological-
maintained in PLWH who ly suppressed HIV-infected individuals
switched to B/F/TAF” In terms of safety profile, there were aged ≥65 years,” they added.

B/F/TAF is a single-tablet regimen

that has few drug-drug interactions and
a high barrier to resistance. Being in
small tablet size with no food restrictions
for dosing, this combination regimen
presents a convenient potential option,
in particular for the elderly PLWH, the
researchers pointed out.

The phase IIIb, international,

open-label study enrolled 86 PLWH
aged ≥65 years (median age 69 years,
13 percent female) who were virologi-
cally suppressed (defined as HIV-1 RNA
<50 copies/mL). They were originally
receiving either elvitegravir/cobicistat/
emtricitabine/tenofovir alafenamide
(E/C/F/TAF) or a tenofovir disoproxil fu-
marate (TDF)-based regimen and were
switched to B/F/TAF. Majority of them

46
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DOCTOR || DECEMBER ISSUE
 CONFERENCE COVERAGE
HIV Glasgow 2020 Virtual Meeting • October 5-8

HIV ups risk of death from COVID-19

ELVIRA MANZANO COVID-19. “We applied for access to differences were noted between the two

H
its very large database, which connects groups in terms of respiratory rate, oxy-
IV patients hospitalized for data from all patients hospitalized with gen need, or presence of chest infiltrates.
COVID-19 are at a higher risk for either known or suspected COVID-19.”
mortality than those hospitalized When stratified by age, the mortality
without HIV in a new study reported at “This is our first analysis in what will rate was higher in younger HIV-positive
HIV Glasgow 2020. be an ongoing process,” Geretti point- patients than those HIV-negative. “HIV
ed out. “What is important is that we patients younger than 70 years of age
This was the key finding from an anal- demonstrated that there is really a need had a twofold risk of mortality. These are
ysis of data from the ISARIC WHO Clini- to look more carefully into this population people who had diabetes with complica-
cal Characterisation Protocol (UK) study. with HIV.” tions and are likely obese.”

HIV-positive status was associat- Twofold risk if younger Mortality at day 28 was significantly
ed with a 63-percent increased risk of and obese higher in HIV-positive patients <50 years
death at day 28 in patients hospitalized Of 47,539 patients in the database, 115 of age (p=0.004) and those 50– 59 years
with COVID-19 from January 17 to June (0.24 percent) were HIV-positive. Of this, of age (p=0.05).
4, 2020 in the UK. This was particularly 103 (89.6 percent) had a history of an-
evident in HIV-positive patients younger tiretroviral treatment (ART). To validate their findings, Geretti and
than 70 years old, said lead investigator team plan to expand their data set to
Dr Anna Maria Geretti, professor of virol- The HIV patients were younger, with 100 more patients. “We need greater
ogy and infectious diseases, University of a median age of 55 vs 74 in those with- numbers … we hope the research com-
Liverpool in Liverpool, UK. [HIV Glasgow out HIV (p<0.001) on admission. HIV munity will be stimulated to take a clos-
2020, abstract O422] patients also had a higher prevalence er look at this information, and merge
of obesity, moderate-to-severe liver dis- other data … we need to tease out what
The cumulative incidence of mortality ease, higher lymphocyte counts, and factors are causing this increased risk of
at day 28 was 25.2 percent in HIV-posi- C-reactive protein, plus a host of sys- mortality in this group,” Geretti said. “As
tive patients vs 32.1 percent in HIV-neg- temic symptoms. No HIV patients seem to be at increased
ative patients (p=0.12). risk, HIV status should be factored into
the clinical management.”
Anxiety prompts investigation
Geretti and team investigated whether
HIV status is important in COVID-19 out-
comes. “This was because of the anxiety
manifested by our patients … we want-
ed to gather evidence-based information
that would guide them,” Geretti said.

ISARIC, she said, is a UK-wide con-

sortium of doctors and scientists com-
mitted to providing information about
What if HIV status is not known to
COVID-19 patients? “Run a test. That
would be good practice,” she recom-
mended.

47
57
DOCTOR || DECEMBER ISSUE
 Sponsored Interview

Influenza vaccination key to preventing

coinfection with COVID-19, reducing
burden on healthcare system
In an interview, Dr Eric Lee Kim Hor, a consultant paediatrician from Pantai Hospital Kuala Lumpur,
spoke on the importance of vaccination in the prevention of influenza among children, resulting in the
prevention of coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting
in coronavirus disease (COVID-19) as well as reduction of burden on the healthcare system.

Dr Eric Lee Kim Hor 2.Based on your study and other studies on
Consultant Paediatrician
influenza, how common is influenza among
Pantai Hospital Kuala Lumpur children in Malaysia?
According to the surveillance data submitted to the World Health
Organization (WHO), the number of specimens positive for influenza
1.What are the similarities and differences in Malaysia were highest in Q4 2019—as high as almost 50
specimens in week 51; early Q1 2020 also showed high numbers of
in characteristics of influenza and COVID-19
specimens positive for influenza.6 As of January 2020, the Selangor
among children? state education department reported 863 cases of influenza
The key influenza symptoms comprising fever, dry cough and A(H1N1) among schoolchildren from 278 schools in 10 locations.
shortness of breath are similar to COVID-19 symptoms.1 Other affected states included Penang, Perak, Pahang, Kedah, and
Sabah. In Johor, 138 students showed influenza-like illness (ILI).7
However, COVID-19 in children may have a varied clinical
presentation (Figure 1).2 Other documented symptoms included Earlier studies conducted in University Malaya (UM) from 1982 to
tachypnoea, nasal congestion, rhinorrhoea, wheezing, diarrhoea, 2008 on >10,000 respiratory samples from children aged ≤5 years
vomiting, headache, and fatigue.3 who were admitted with viral respiratory tract infections (RTI) found
26.4% of samples were positive for respiratory viruses. The most
common viruses were respiratory syncytial virus (RSV, 70.6%),
Figure 1. Clinical symptoms seen in children with parainfluenza (13.2%) and influenza (11.0%). Immunofluorescence
COVID-192 staining and viral cultures were the diagnostic methods used. The
study authors concluded that RTI were significant causes of morbidity
Study
ID Proportion (95% CI) in hospitalized children and were likely to be underdiagnosed before
Fever 2010.8
Jie et al., 61.54 (51.54, 71.53)
Yaoling et al., 25.22 (17.28, 33.15)
Liu et al., 40.00 (9.64, 70.36)
Ya-nan et al., 71.43 (37.96, 104.89)
Jiehao et al., 80.00 (55.21, 104.79) Surveillance and testing using the real time reverse transcriptase
Kai et al., 35.71 (10.61. 60.81)
Wei et al.,
Mengqi et al.,
20.00 (-15.06, 55.06)
40.00 (-2.94, 82.94)
polymerase chain reaction (PCR) test have revealed a clearer
Xuegong et al.,
Haiyan et al.,
64.52 (47.67, 81.36)
36.11 (20.42, 51.80) picture on the extensiveness of influenza in Malaysia.9
Qinxue et al., 33.33 (2.54, 64.13)
Yi et al., 70.00 (41.60, 98.40)
Fang et al., 52.00 (32.42, 71.58)
Subtotal (I-squared = 79.1%, p = 0.000)
In 2015–2017, >8,000 nasopharyngeal swab specimens were
Dry cough
Jie et al.,
Yaoling et al.,
56.04 (45.85, 66.24)
40.87 (31.88, 49.85)
collected from patients aged <18 years throughout Malaysia with
Liu et al.,
Ya-nan et al.,
10.00 (-8.59, 28.59)
71.43 (37.96, 104.89) acute respiratory infection (ARI); >4,000 were positive for respiratory
Jiehao et al., 60.00 (29.64, 90.36)
Kai et al.,
Wei et al.,
7.14 (-6.35, 20.63)
20.00 (-15.06, 55.06)
viruses. While the most common infections were due to enterovirus/
Mengqi et al.,
Xuegong et al.,
40.00 (-2.94, 82.94)
45.16 (27.64, 62.68) rhinovirus (24.4%), which cause the common cold, it was surprising
Haiyan et al., 19.44 (6.52, 32.37)
Qinxue et al.,
Yi et al.,
11.11 (-9.42, 31.64)
50.00 (19.01, 80.99)
to note that the second commonest infection was influenza (17.1%).
Fang et al.,
Subtotal (I-squared = 80.9%, p = 0.000)
44.00 (24.54, 63.46)
35.09 (23.62, 46.57) The number of influenza cases were significant, and the majority of
Diarrhoea and / or vomiting
Jie et al., 10.99 (4.56, 17.41)
patients were ≤6 years old (Figure 2).9
Yaoling et al., 2.61 (-0.30, 5.52)
Ya-nan et al., 57.14 (20.48, 93.80)
Xuegong et al., 9.68 (-0.73, 20.08)
Haiyan et al., 5.56 (-1.93, 13.04)
Qinxue et al., 22.22 (-4.94, 49.38)
Yi et al.,
Fang et al.,
30.00 (1.60, 58.40)
20.00 (4.32, 35.68) Figure 2. Type of virus infection in respective age
Subtotal (I-squared = 68.8%, p = 0.002) 11.30 (4.82, 17.79)
groups9
Sore throat
Ya-nan et al., 14.29 (-11.64, 40.21)
Jiehao et al., 40.00 (9.64, 70.36)
Wei et al.,
Xuegong et al.,
20.00 (-15.06, 55.06)
6.45 (-2.20, 15.10) Type of virus infection, against age group
Haiyan et al., 5.56 (-1.93, 13.04)
Qinxue et al.,
Yi et al.,
11.11 (-9.42, 31.64)
40.00 (9.64, 70.36) 700
Subtotal (I-squared = 38.3%, p = 0.136) 12.24 (4.02, 20.45)
600 Influenza
RSV
NOTE: Weights are from random effects analysis. 500 Coronavirus
Infection Cases

Parainfluenza
400 Enterovirus/ Rhinovirus

Although anosmia (loss of smell) has been noted as an early 300

symptom of COVID-19 infection, it’s not easy to screen young
children for loss of smell or taste hence, the difficulty in detecting 200
anosmia in young children.4 100

0
Interestingly, some children may mount an immune response to <1 1-3 4-6 7-9 10-12 13-15 16-18
SARS-CoV-2 while remaining asymptomatic or have a comparatively Age group
milder disease.5
 Sponsored Interview

Another retrospective study in collaboration with Pantai Premier 4.Why is influenza vaccination important
Pathology looked at >10,000 nasopharyngeal swab samples from 12
during the COVID-19 pandemic? How would
private laboratories in 2016–2019 throughout Malaysia. This study
included children aged ≤18 years with RTI. About 2,000 samples you advise your patients and their families
(25%) were positive for influenza, which mostly affected children to continue with their annual influenza
aged <6 years (Figure 3).10 Almost 40% of preschool children with vaccination?
ARI were hospitalized due to influenza as one of the main causes.10 Studies have shown influenza is one of the most common
viral coinfections among patients with COVID-19.2,3,15 Influenza
vaccination in young children are likely to have a significant impact
Figure 3. Influenza distribution by age10 on their morbidity and economic burden.9,10,14 Children aged <6
years are at the highest risk of influenza, so it is best to target
them for influenza vaccination,9,10 to prevent the double burden of
350 2500 influenza and COVID-19. Further, we do not really know about the
300 long-term complications of coinfections.
2000

Total screened, n
250
Influenza vaccination can boost children’s immunity because
1500
positive, n

200 influenza can cause their immunity to weaken and make them
150 1000
vulnerable for other infections, including COVID-19. It is important
to maintain children’s health as much as possible especially before
100
500 they return to school. One mother whose child was vaccinated
50 against the northern strain of influenza end of 2019, returned for the
0 0 southern strain vaccination before her child resumed school. As a
≤6 7m- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 doctor, I used to educate parents about the benefits of the influenza
m <1y
Age vaccination, but now more parents ask me when their children
can take the influenza vaccination and also remind me about their
Influenza A Influenza A/H1 Influenza A/H1-2009
Influenza A/H3 Influenza B Total positive (A+B)
children’s yearly influenza vaccination.
total screened
Vaccinating children against influenza would also reduce the risk of
children spreading influenza to their susceptible grandparents who
are at higher risk of having severe COVID-19 and may be staying in
the same household.
3.Please elaborate on influenza-related
burden of disease.
Some children with influenza have been shown to develop 5.What are the recommendations from the
complications such as pneumonia, dehydration, worsening of WHO’s Strategic Advisory Group of Experts
preexisting chronic medical conditions like heart disease or asthma; (SAGE) on influenza vaccination during the
encephalopathy, and sinusitis and ear infections. In rare severe
COVID-19 pandemic?
cases, these complications can lead to death.11
According to the SAGE interim recommendations, children are still
considered a priority group for influenza vaccination due to the risk
A study during the 2009 influenza A(H1N1) pandemic among of severe influenza especially among those aged 6 months to 2
children ≤12 years old found 103 (8.3%) of 1,244 children years. The recommendation is to continue vaccinating children with
admitted for influenza A(H1N1) had influenza-related neurological influenza vaccines.16
manifestations. Out of the 103 children, 69 (66.9%) had febrile
seizures; 16 (15.5%) had breakthrough seizures with underlying
epilepsy; 14 (13.6%) had influenza-associated encephalopathy; 6.Data from the southern hemisphere
and 4 (3.9%) had acute necrotizing encephalopathy of childhood indicated there was a reduction in influenza
(ANEC). Four children died while three had permanent neurological
cases during the lockdown period. Have you
sequelae.12
observed this trend in your practice? Why
Researchers in UM looking at children admitted due to influenza was there a reduction in influenza cases?
found that 36.4% had underlying medical problems such as asthma. During the 4 months of movement control order or lockdown, social
More younger children (<12 months old) had severe disease. isolation and social distancing was widely practiced, and children
Influenza had a considerable impact because healthy children as were at home. The number of influenza cases had reduced. Parents
well as those with underlying medical conditions were among those who brought their children for vaccination after the lockdown period
hospitalized.13 had ended, informed that their child did not have any ILI during the
lockdown period.
Influenza has a greater impact on young children, their family and
the healthcare system than other respiratory viruses which cause The lockdown actually helped to reduce the number of influenza
ILI.14 Firstly, influenza lasted an average of 9.54 days compared to cases. This together with the heightened parental awareness of
8.50 days caused by ILI (p=0.005). Medications were used more the importance of influenza immunisation following the severe
frequently to treat fever and cough due to influenza. Absenteeism outbreak in Q4 2019 and Q1 2020 which caused a shortage of
from school/ day care or work was longer with influenza. Parents influenza vaccines and antiviral medication, resulted in more
also took their child to the GP or emergency department more often. parents bringing their children for influenza vaccination. This
It is a significant economic burden on the family which falls back to increase in the number of people vaccinated may have also
the community.14 contributed to the lower number of influenza cases in end Q1 2020.
 Sponsored Interview

7.What is the impact of patients with

influenza seeking treatment and adding to
the already burdened healthcare system, Key takeaways
which is trying to manage the COVID-19 • Fever, dry cough and shortness of breath are similar
symptoms in children with influenza or COVID-19.
pandemic? How does influenza vaccination
• Influenza is common among children but
assist the healthcare system in this underdiagnosed prior to the availability of PCR testing.
situation? • Children, especially those aged <12 months, are at
Influenza is one of the main causes for ARI in children <6 years risk of morbidity and mortality resulting in economic
old with 39% hospitalized cases. Public health authorities should implications to their family and the community.
consider introducing influenza vaccination to preschool children <6 • Influenza vaccination during this COVID-19 pandemic
years old or those in primary one to reduce child morbidity and the can prevent morbidity among children and economic
economic burden to family and community.10 burden.
• Children are a priority group for influenza vaccination
As a personal experience from the influenza outbreak in Q1 2020, due to the risk of severe influenza.
my paediatric patients were admitted to the adult wards due to • The number of influenza cases reduced during the
shortage of beds. Thus, if we can prevent influenza infection among lockdown period due to social distancing.
children by vaccinating them, the reduced bed occupancy would • Influenza vaccination for children can prevent influenza
free the beds for other cases in a pandemic situation. and the related complications while boosting their
immunity during this COVID-19 pandemic.
Influenza vaccination also results in fewer cases of ILI, which in • Influenza vaccination can lead to reduced burden on
turn, reduces the number of people tested for COVID-19 due to the healthcare system during this COVID-19 pandemic.
overlapping symptoms, and prevents the shortage of COVID-19
test kits and unnecessary use/ wastage of personal protective
equipment (PPE).

References: 1. Song X, et al. JAMA Netw Open 2020;3:e2020495. 2. Zheng B, et al. Pediatric Pulmonology 2020;1–10. 3. Zimmermann P, Curtis N. The Pediatric infectious Disease
Journal 2020;39:469–477. 4. Hall A, et al. Arch Dis Child 2020 August 4. doi:10.1136/archdischild-2020-319971. 5. Swann OV, et al. BMJ 2020;370:m3249. 6. World Health Organization.
Influenza Laboratory Surveillance Information. Available at: http://apps.who.int/flumart/Default?ReportNo=7 Accessed 25 October 2020. 7. The Star. Influenza: Selangor still has highest
number of cases among schoolchildren. Available at: https://www.thestar.com.my/news/nation/2020/01/20/influenza-selangor-still-has-highest-number-of-cases-among-schoolchildren
Accessed 26 October 2020. 8. Khor CS, et al. BMC Pediatrics 2012;12:32. 9. Low YL, et al. Epidemiology of Respiratory Infection in Paediatrics: 3 Years Retrospective Study in Malaysia.
Presented at: 37th Annual European Society for Paediatric Infectious Diseases (ESPID) Meeting; 6–11 May 2019; Ljubljana, Slovenia. 10. Low YL, et al. Epidemiological Studies of
Influenza Infection Among Children in Malaysia. Presented at: OPTIONS X for the Control of Influenza; 28 August–1 September 2019; Singapore. 11. Centers for Disease Control and
Prevention (US). Flu & Young Children. Available at: https://www.cdc.gov/flu/highrisk/children.htm Accessed 26 October 2020. 12. Muhammad Ismail HI, et al. Brain Dev 2015;37:120–
129. 13. Sam IC, et al. Int J Infect Dis 2010;14 Suppl 3:e36–e40. 14. Willis GA, et al. Influenza Other Respir Viruses 2019;13:18–27. 15. Lansbury L, et al. J Infect 2020;81:266–275.
16. World Health Organization. WHO SAGE Seasonal Influenza Vaccination Recommendations during the COVID-19 Pandemic. Interim guidance. Available at: https://www.who.int/
immunization/policy/position_papers/Interim_SAGE_influenza_vaccination_recommendations.pdf?ua=1 Accessed 17 November 2020.

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 HUMOUR
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ourpoor
poorhealth
healthon
onthe
the
environment.
environment.When
WhenI Iwas
wasyoung,
young,wewedidn’t
didn’thave
haveany
any “If
“Ifthere’s
there’snothing
nothingelse
elsewe
weneed
needto
tofix,
fix,
environment
environmentand
andpeople
peoplegot
gotsick
sickjust
justthe
thesame!”
same!” I’m
I’mgoing
goingfor
forlunch!”
lunch!”

64
64
63
DOCTOR | ||DECEMBER
DOCTOR DECEMBERISSUE
ISSUE
 CALENDAR

JANUARY 2021 JANUARY 2021 FEBRUARY 2021

15-17
FRIDAY–SUNDAY
21-24
THURSDAY–SUNDAY
4-6
THURSDAY–SATURDAY

American Society of Clinical Crohn’s & Colitis Congress – 30th Annual Conference of the
Oncology Gastrointestinal Connecting Virtually Asian Pacific Association for
(ASCO GI) Cancers Symposium Website: www.crohnscolitiscongress.org the Study of the Liver (APASL) –
– Virtual Virtual
Email: meetings@asco.org Tel: 65 6346 4402
Website: meetings.asco.org/gi/statement- Email: secretariat@apasl2021bangkok.org
2021-gastrointestinal-cancers-symposium Website: www.apasl2021bangkok.org

FEBRUARY 2021 FEBRUARY–MARCH 2021 MARCH 2021

11-13
THURSDAY–SATURDAY
26-1
FRIDAY–MONDAY
12-13
FRIDAY–SATURDAY

ASCO Genitourinary (GU) American Academy of Allergy, Highlights of American Society

Cancers Symposium – Virtual Asthma & Immunology (AAAAI) of Hematology (Highlights of
Email: meetings@asco.org Annual Meeting – Virtual ASH) in APAC – Virtual
Website: meetings.asco.org/gu/statement- Tel: 414 272 6071 Tel: 866 828 1231
2021-genitourinary-cancers-symposium Website: www.aaaai.org/ Fax: 202 776 0545
Announcements/2021AM Website: www.hematology.org/meetings/
highlights/asia

APRIL 2021 APRIL 2021 APRIL 2021

2-4
FRIDAY–SUNDAY
4-6
SUNDAY–TUESDAY
8-10
THURSDAY–SATURDAY

National Heart Association of Asia-Oceania Conference on ENDO KL 2022

Malaysia Congress 2021 (NHAM Obesity and Malaysian Association Website: http://endokl2022.org/
Congress 2021) for the Study of Obesity Scientific Postponed to 6-8 October 2022
Location: Kuala Lumpur Convention Centre Conference (AOCO-MASO 2021)
Info: NHAM Congress Secretariat Location: Hotel Istana, Kuala Lumpur
Tel: 03 7931 2131 Info: Conference Secretariat
Website: www.nham-conference.com Tel: 03 9769 2471
Email: maso.obesity@gmail.com
Website: www.aocomaso2021.com

64
DOCTOR | DECEMBER ISSUE