Rheumatoid arthritis

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Review

‘Should we stop or continue

conventional synthetic (including
glucocorticoids) and targeted DMARDs
before surgery in patients with
inflammatory rheumatic diseases?’
Susan M Goodman ,1 Michael D George2

To cite: Goodman SM, George ABSTRACT

MD. ‘Should we stop or continue Total hip and total knee arthroplasty) remain important
Key messages
conventional synthetic
interventions to treat symptomatic knee and hip damage ► Arthroplasty use remains prevalent for patients
(including glucocorticoids) and
in patients with rheumatoid arthritis, with little change
targeted DMARDs before with rheumatoid arthritis (RA), and the majority
surgery in patients with in utilisation rates despite the increasingly widespread
use of potent conventional synthetic disease-modifying
are receiving biologic and conventional DMARDs
inflammatory rheumatic
anti-rheumatic drugs (csDMARDs) and targeted DMARDs and glucocorticoids at the time of surgery.
diseases?’. RMD Open 2020;6:
e001214. doi:10.1136/ including Janus kinase inhibitors and biologics. The ► Risk of surgical site infection including
rmdopen-2020-001214 majority of patients are receiving these prosthetic joint infection is multifactorial for
immunosuppressing medications and glucocorticoids at patients with RA and includes active RA,
► Prepublication history and
supplemental material for this
the time they present for arthroplasty. There is minimal smoking, comorbidities, glucocorticoids and
paper are available online. To randomised controlled trial data addressing the use of immunosuppressive therapy.
view these files, please visit DMARDs in the perioperative period, yet patients and ► Flares of RA are frequent after arthroplasty, and
the journal online (http://dx.doi. their physicians face these decisions daily. This paper
org/10.1136/rmdopen-2020-
the link to medication management is not
reviews what is known regarding perioperative established; patients tend to prioritise avoiding
001214).
management of targeted and csDMARDs and
infections over risking flares.
Received 20 April 2020 glucocorticoids.
► Current studies of the interval between a biologic
Revised 3 June 2020
Accepted 5 June 2020 infusion and surgery have not demonstrated
a differential infection risk for patients receiving
INTRODUCTION recent versus remote infusions.
The standard of care for patients with rheuma-
toid arthritis (RA) is to gain control of the dis- other csDMARDs and 32% were receiving glu-
© Author(s) (or their
ease by escalating or changing disease- cocorticoids at the time of joint replacement
employer(s)) 2020. Re-use modifying anti-rheumatic drug (DMARD) ther- surgery.3 While use of both conventional and
permitted under CC BY-NC. No apy until remission or low disease activity is targeted DMARDs has increased, and the rates
commercial re-use. See rights achieved. Currently, most patients with RA are of upper extremity and small joint surgery have
and permissions. Published receiving one or more conventional synthetic decreased, the rates of total hip (THA) and total
by BMJ.
1
DMARDs (csDMARDs) or a combination knee arthroplasty (TKA) have not.2 4 In one
Department of Medicine,
including a targeted therapy to achieve this recent study using propensity matching and
Hospital for Special Surgery,
Weill Cornell Medicine, New goal.1 The treatment of RA has changed sub- adjusting for disease activity, tumour necrosis
York, USA stantially over the past decades. In 1986–1989, factor inhibitor (TNFi) use was not associated
2
Department of Biostatistics, 1% of patients with RA used methotrexate as the with decreased rates of THA or TKA.5 There-
Epidemiology and Informatics, first-line csDMARD and approximately 2.5% of fore, patients with RA continue to undergo
Hospital of the University of
patients with RA were on a combination of two THA and TKA, despite high utilisation of tar-
Pennsylvania, Philadelphia,
Pennsylvania, USA csDMARDs.2 By 2006–2011, 70% of patients geted and csDMARDs and glucocorticoids,
were on methotrexate, and 22.5% of patients which most patients are taking at the time of
Correspondence to were on combinations of two to three surgery. A careful thorough medical evaluation
Susan M Goodman, Department csDMARDs or a csDMARD and a targeted is also essential in these patients but will not
of Medicine, Hospital for Special
Surgery, Weill Cornell Medicine,
DMARD.2 3 By 2013–2016, 50% of patients be addressed in this paper.6 This paper
New York 10021, USA; Good with RA undergoing arthroplasty were on tar- provides an overview of the current data sup-
mans@hss.edu geted DMARDs, 80% were on methotrexate or porting perioperative management of targeted

Goodman SM, George MD. RMD Open 2020;6:e001214. doi:10.1136/rmdopen-2020-001214 1

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and csDMARDs and glucocorticoids and the current Multiple other factors contribute to infection risk, such
recommendations for perioperative medication manage- as age, comorbidities (eg, obesity, smoking, diabetes) and
ment. The majority of the data presented comes the volume of surgeries performed by the hospital and
from studies of patients with RA undergoing joint surgeon (figure 1).16 Risks for infection are additive. For
replacement. instance, there is a fourfold increase in the risk of PJI with
a body mass index (BMI)>40 kg/m2 (OR 4.13, 95% CI 1.3
to 12.88; p=0.01). If the patient with a BMI>40 kg/m2 is
also an active smoker, the risk is higher (OR 7.52, 95% CI
RISK OF INFECTION
1.69 to 33.4, p=0.04). Staphylococcus aureus colonisation is
Medication management at the time of surgery seeks to
increased in patients with RA on biologics (OR 1.80, 95%
balance the risk of infection attributed to targeted and
CI 1.007 to 3.22, p=0.04) and S. aureus colonisation
csDMARDs against the risk of flares of inflammatory
increases the risk of PJI (OR 2.36, 95% CI 1.13 to 4.88,
disease.7 8 Patients with RA have an increased risk of
p=0.02).17 If the colonised patient is also a smoker with
infection in general, and this risk is increased in patients
a BMI≥30 kg/m2, the risk increases further (OR 12.76–-
treated with certain immunosuppressants, including
66.16, p=0.017).18 While medication management
glucocorticoids, and in patients with severe or active
around the time of surgery is of particular interest
disease.7 9–11 Risk associated with disease activity is espe-
because of the potential for intervention, it is important
cially relevant since most patients have active disease at
to remember that infection risk in patients with RA is
the time of arthroplasty, with a mean Disease Activity
multifactorial.
Score-28 (DAS28) Erythrocyte Sedimentation Rate of
3.7, indicating moderate disease activity, despite
a mean disease duration of almost 15 years.3 The major- POSTOPERATIVE FLARES
ity of prosthetic joint infections (PJI) occur during the Flares are common after THA and TKA; 63% of patients
first 1–2 years after surgery, with an overall incidence of with RA report a flare within 6 weeks of surgery, and
1.55%, and are attributed to infections introduced at the a third were rated as severe by those with flares.3 19
time of surgery or as a result of delayed wound healing; Patients who reported flares had higher disease activity
the incidence of late infections is significantly lower at than those without and a similar pattern as patients who
0.46%.12 Patients with RA have a 50–80% greater risk of had not undergone surgery, and patients in both surgi-
PJI than patients with osteoarthritis, and also have cal and non-surgical groups self-manage their flares
greater risk beyond the early period.9 13 14 For the pur- and rarely consult their rheumatologist.20–22 Patients
poses of perioperative management, however, early describe flare events as severe and disabling, and flares
infections are most relevant since delayed infections are associated with radiographic progression.21 23 How-
are more commonly related to subsequent episodes of ever, using a measure commonly used to assess THA
sepsis or bacteremia and are not expected to be influ- and TKA outcomes, the Hip Disability (HOOS) and
enced by perioperative medication management Knee Injury OA Outcomes Scores (KOOS), flares in
decisions.15 the post-operative period were not an independent

Figure 1 Risk factors for postoperative infection. DMARDs, disease-modifying anti-rheumatic drugs; S. aureus, Staphylococcus
Aaureus.

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risk factor for pain and function measured at 1 year did not significantly increase PJI risk (SHR=1.61
after surgery.24 Baseline DAS28 predicted 1-year (0.70–3.69)).30 Moreover, a meta-analysis demonstrated
HOOS/KOOS pain and function; each 1 unit increase that postoperative infection risk was not decreased in
in DAS28 worsened 1-year pain by 2.41 (SE=1.05, those patients stopping TNFi prior to orthopaedic
p=0.02) and 1-year function by 4.96 (SE=1.17, surgery.32 Less data exist for other surgery types, many of
p=0.0001), suggesting that active sustained disease is which may be associated with higher risks of complications.
a greater problem than flares.24 In addition while One study of patients with inflammatory bowel disease
numerically more flarers used targeted DMARDs, stop- undergoing abdominal surgery found an increased rate of
ping them did not predict flares, and continuing meth- infectious complications (although not serious infections)
otrexate in this cohort was not protective.3 in patients receiving a TNFi,33 but a similar study found that
Optimisation prior to surgery should include control- use of biologics use was not associated with wound compli-
ling RA disease activity when possible. Moreover, when cations and that the timing of biologics before surgery was
a patient panel comprised patients with RA and juvenile not associated with outcomes.34 Whether data in patients
arthritis were convened to advise the American College undergoing abdominal surgery to treat an inflammatory
of Rheumatology (ACR) and the American Association gastrointestinal condition are applicable to patients with
of Hip and Knee Surgeons (AAHKS) in the formulation RA is uncertain. A recent study using administrative data
of a guideline for perioperative medication manage- evaluated patients with RA undergoing hip fracture repair,
ment, they were unanimous in their opinion that any abdominopelvic surgery, or cardiac surgery and found no
potential increase in infection risk was worse than increase in the risk of 30-day readmission, hospitalised infec-
a flare of their disease.24 25 Taken together, these data tion, pneumonia or wound complications in patients receiv-
suggest that flares in the postoperative period may not ing a TNFi or in patients receiving a non-TNFi targeted
be linked to medication management and that patients DMARD compared with patients receiving methotrexate
prioritise the risk of infection over flares after arthro- without one of these therapies.35 Similar to what has been
plasty. Table 1 summarises the medications in current seen in studies of arthroplasty, the timing of infliximab
use in rheumatology practice and recommendations infusions prior to surgery was not associated with adverse
included in the ACR/AAHKS Guideline.26 outcomes.35
While it remains uncertain whether interruption of
a TNFi before surgery can improve postoperative out-
TNF INHIBITORS comes, the ACR/AAHKS guideline for patients under-
Patients receiving TNFi have an increased risk of going elective TKA and THA achieved consensus
infection,11 and studies have demonstrated that patients between the surgeons, rheumatologists and infectious
undergoing TKA or THA who receive TNFi were at an disease specialists, recommending that all biologics be
increased risk of infection compared to those with no withheld for a short duration with surgery planned for
TNFi exposure.11 27 Using pooled data in a meta-analysis the end of the dosing cycle. This recommendation
representing 3681 patients with and 4310 without a recent assumes that high doses of medications suppress the
exposure to TNFis at the time of surgery, the TNFi exposed immune system more than lower doses and that the dos-
group had higher risk of developing a surgical site infection ing interval better reflects the duration of immunosup-
compared with patients not exposed to TNFi (OR 2.47, 95% pression that the blood half-life. Medications can be
CI 1.66 to 3.68. p<0.0001).28 However, the included studies restarted at approximately 14 days after surgery when
compared those whose disease was severe enough to treat the wound has healed, sutures and staples are out, there
with a TNFi compared with those who were likely to have is no swelling or drainage and there are no clinical signs
milder disease, and disease activity and severity are also risk of infection.26
factors for infection.7 29 30 Administrative data sets contain
billing data for TNFi infusions that permits the time
between the TNFi dose and surgery to be accurately deter- OTHER TARGETED DMARDS
mined and compared, so equivalent groups could be ana- Less data exist to inform management of other tar-
lyzed. There was no increase in infection within 30 days of geted DMARDs. An administrative claims study examin-
surgery in patients who received infliximab <4 weeks prior ing 1958 patients with RA receiving abatacept infusions
to surgery compared to 8–12 weeks (propensity adjusted OR before arthroplasty found no difference in postopera-
0.90, 95% CI 0.60 to 1.34). Similarly, there was no increase tive infection in patients who received abatacept
in the rate of PJI in patients receiving infliximab infusions 4–8 weeks (one dosing interval) versus <4 weeks before
<4 weeks versus 8–12 weeks (3.1 vs 2.9 per 100 person-years, surgery (OR 0.93 (0.65–1.34) for 30-day hospitalised
HR 0.98, 95% CI 0.52 to 1.87) (figure 2).31 Using the Danish infection, HR 1.29 (0.62–2.69) for PJI within
arthroplasty registry and linking to the DANBIO rheumatol- 1 year).36 A previous registry described low infection
ogy register that contains information about RA disease and risk for abatacept treated patients and no relationship
severity and biologics use, patients with RA had an increased between time from infusion to surgery.37 An additional
risk of PJI (confounder adjusted sub-HR (SHR)=1.46 study using the same data sources examined a cohort
(1.13–1.88)).30 However, treatment with biologic DMARDs of 9911 patients with a prescription or infusion of

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Table 1 Medications included in the American College of Rheumatology/American Association of Hip and Knee Surgeons
Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing
Elective Total Hip or Total Knee Arthroplasty*
DMARDs: CONTINUE these medications through surgery Dosing interval Continue/Withhold
Methotrexate Weekly Continue
Sulfasalazine One or two times per Continue
day
Hydroxychloroquine One or two times per Continue
day
Leflunomide (Arava) Daily Continue
Doxycycline Daily Continue
BIOLOGICS: STOP these medications prior to surgery and
schedule surgery at the end of the dosing cycle. RESUME
medications at minimum 14 days after surgery in the
absence of wound healing problems, surgical site infection Schedule Surgery (relative to
or systemic infection. Dosing interval last biologic dose administered)
Adalimumab (Humira) 40 mg Every 2 weeks Week 3
Etanercept (Enbrel) 50 mg or 25 mg Weekly or two times per Week 2
week
Golimumab (Simponi) 50 mg Every 4 weeks (SQ) or Week 5
Every 8 weeks Week 9
(intravenous)
Infliximab (Remicade) 3 mg/kg Every 4, 6 or 8 weeks Week 5, 7 or 9
Abatacept (Orencia) weight-based 500 mg; intravenous Monthly (intravenous) or Week 5
1000 mg; SQ 125 mg Weekly (SQ) Week 2
Rituximab (Rituxan) 1000 mg 2 Doses 2 weeks apart Month 7
every 4–6 months
Tocilizumab (Actemra) intravenous 4 mg/kg; Every week (SQ) or every Week 3
SQ 162 mg 4 weeks (intravenous) Week 5
Anakinra (Kineret) SQ 100 mg Daily Day 2
Secukinumab (Cosentyx) 150 mg Every 4 weeks Week 5
Ustekinumab (Stelara) 45 mg Every 12 weeks Week 13
Belimumab (Benlysta) 10 mg/kg Every 4 weeks Week 5
Tofacitinib (Xeljanz) 5 mg: STOP this medication 7 days prior to Daily or two times per 7 days after last dose
surgery. day
SEVERE SLE-SPECIFIC MEDICATIONS: CONTINUE these
medications in the perioperative period. Dosing interval Continue/Withhold
Mycophenolate Two times per day Continue
Azathioprine Daily or two times per Continue
day
Cyclosporine Two times per day Continue
Tacrolimus Two times per day Continue
(intravenous and PO)
NOT-SEVERE SLE: DISCONTINUE these medications in the
perioperative period Dosing interval Continue/Withhold
Mycophenolate Two times per day Withhold
Azathioprine Daily or two times per Withhold
day
Cyclosporine Two times per day Withhold
Tacrolimus Two times per day Continue
(intravenous and PO)
Dosing intervals obtained from prescribing information provided online by pharmaceutical companies.
*Reprinted with permission from Goodman SM, Springer B, Guyatt G, et al. American College of Rheumatology/American Association of Hip and
Knee Surgeons Guideline for the Perioperative Management of Anti-rheumatic Medication in Patients with Rheumatic Diseases Undergoing
Elective Total Hip or Total Knee Arthroplasty. Arthritis Rheumatol. 2017 Aug 69(8);1538–51.
DMARDs, disease-modifying anti-rheumatic drugs; PO, per os; SLE, systemic lupus erythematosus; SQ, subcutaneous.

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abatacept, adalimumab, etanercept, infliximab, rituxi-
mab or tocilizumab who underwent THA or TKA and
found no difference in hospitalised infection, PJI or
readmission between the biologics (figure 3).38
Although the study cohort contained few rituximab-
and tocilizumab-treated patients, registries have pro-
vided additional data. Data from patients treated with
tocilizumab who underwent surgery were collected
from a routine care registry. The mean interval
between surgery and the last tocilizumab infusion was
4.94±1.74 weeks, with few complications reported.39
However, surgeons may not be aware of the direct
effect of tocilizumab on the C reactive protein and
blunting of the temperature curve, requiring greater
vigilance in diagnosing infection postoperatively.40
Figure 2 Kaplan-Meier curves comparing incidence of A total of 201 patients in a rituximab registry under-
prosthetic joint infection in patients with RA undergoing total went surgery, 58% were orthopaedic procedures and 9
hip or knee arthroplasty based on the time between the last patients (6.7%) had complications. There was no sig-
infliximab infusion and surgery (infliximab stop time)31 nificant difference in the median interval between the
(Reproduced with permission). RA, rheumatoid arthritis. rituximab infusion and surgery for patients with

Figure 3 Associations between the type of biologic a patient was receiving and risks of postoperative outcomes from inverse
probability weighted models31 (Reproduced with permission).

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complications (6.43 months (IQR 4.46–7.6 months)) Other immunosuppressants such as azathioprine,
and without (6.49 months (IQR 3.91–8.74 months)) mycophenolate, cyclosporine and tacrolimus are used
(p=0.99). Included cases were few, and no information more commonly in autoimmune rheumatic diseases
regarding immunoglobulin levels was available.41 As other than RA (such as systemic lupus erythematosus).
low immunoglobulin levels increase infection risk, mea- These therapies may be associated with greater infection
suring immunoglobulin levels prior to surgery and risk than methotrexate, but there are very little data on
replacing when low may be more relevant in mitigating how these treatments might affect postoperative infection
infection risk than extending the interval between sur- risk. One Medicare study of 3339 solid organ transplant
gery and the rituximab infusion.42 For non-surgical patients undergoing arthroplasty who were frequently
patients with RA in the National Databank for Rheu- treated with one or more of these therapies had
matic Diseases, there was no difference in the risk of a greater risk of pneumonia, sepsis and periprosthetic
serious infections in 7210 patients receiving TNFis com- infection compared to controls (2.4% vs 1.0%), but the
pared with 1676 patients on non-TNFi biologics.43 specific contribution of immunosuppression to this risk
There is little information regarding patients receiving could not be determined.51 Given this uncertainty, ACR/
Janus kinase inhibitors such as tofacitinib undergoing AAHKS guidelines recommend continuing these thera-
arthroplasty, although again in non-surgical studies, pies with severe systemic autoimmune disease (in whom
infection risk seems comparable to that seen with the risk of stopping therapy would be high) and stopping
biologics.44 therapy for 1 week prior to surgery in patients with more
The similarity in infection risk among the biologics has mild disease, in consultation with the patients treating
led to the recommendation to plan surgery at the end of the rheumatologist.26
dosing cycle and minimise the time the medications are
withheld, as for the TNFis.26 Given the short half-life of
tofacitinib, recommendations were to withhold treatment GLUCOCORTICOIDS
for 7 days before surgery. Glucocorticoid therapy is widely used in rheumatic dis-
eases. Overall, 65% of patients with RA receive glucocorti-
coids, and a recent surgical series revealed that 87% of
patients undergoing THA or TKA were given glucocorti-
METHOTREXATE AND OTHER CSDMARDS coids at the time of surgery.3 52 Infection is a well-known
Methotrexate, the anchor drug in RA, was studied in risk for patients with RA outside the surgical setting, for
a randomised controlled trial of patients with RA under- whom the risk of serious infection is greatest in those with
going elective orthopaedic surgery, with 388 patients ran- active disease, or with a high exposure to glucocorticoids.
domised into three groups, and complications including In a study using a model of glucocorticoid use that incor-
infections or revisions compared between groups. In porates information relevant to patients with RA about
Group A (continued methotrexate), 2% of patients had duration, intensity and timing of glucocorticoid
complications, 15% of Group B (withheld methotrexate) exposure,7 43 53 high levels of both recent and cumulative
and 10% of 228 patients in Group C (were never on the glucocorticoid use increased infection risk (OR 1.33, 95%
drug) had complications. Flares were also significantly CI 1.22 to 1.45, p<0.001). Glucocorticoids have also been
lower in Group A.45 In addition, the overall safety profile shown to be associated with greater infection risk in
of methotrexate has recently been confirmed in a non- patients with RA undergoing arthroplasty, especially at
rheumatic disease population of diabetics and those with higher doses. In one study, the risk for infection was higher
metabolic syndrome, with no difference in serious infec- with a glucocorticoid dose >15 mg.54 In a study of patients
tions (HR 1.02, 95%CI 0.69 to 1.50) and little difference with RA undergoing elective THA and TKA using large
in infection risk overall (HR 1.15, 95%CI 1.01 to 1.30).46 insurance data sets that include both infusion and pre-
Finally, methotrexate increases the levels of adenosine, scription data, glucocorticoids were associated with a dose-
and studies in animal models demonstrate that adenosine dependent increase in postoperative risk for PJI and ser-
engages receptors on cells and promotes wound healing, ious infection. Propensity-weighted models showed that
adding a theoretical framework to support the continua- use of more than 10 mg of glucocorticoids per day (vs no
tion of methotrexate at the time of surgery.47 glucocorticoid use) resulted in a predicted risk for hospi-
There is little surgical safety data for other csDMARDs, talised infection of 13.25% (95%CI 9.72% to 17.81%) (vs
such as sulfasalazine, hydroxychloroquine or lefluno- 6.78%) and a predicted 1-year cumulative incidence of PJI
mide. A retrospective study of 367 joint surgeries in 204 of 3.83% (95%CI 2.13% to 6.87%) (vs 2.09%).38 In addi-
patients with RA, most of whom were treated with tion, using data from a rheumatology registry linked to an
csDMARDs, demonstrated no increase in surgical site arthroplasty registry revealed that glucocorticoid exposure
infection, and sulfasalazine appeared to decrease infec- was a risk factor for PJI (HR 2.87, 95% CI 1.12 to 7.34), and
tion in another study.48–50 Given the overall safety profile both glucocorticoids and increasing disease activity mea-
of the csDMARDs, the ACR/AAHKS perioperative man- sured as DAS28 (HR 1.49, 95% CI 1.01 to 2.20) were risk
agement guideline recommends continuing these medi- factors for mortality.30 Glucocorticoids at doses >5 mg/day
cations through surgery.26 were also a risk factor for postoperative mortality or

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Figure 4 Flow diagram outlining approach to perioperative management of immunosuppression in patients with rheumatoid
arthritis undergoing elective hip or knee arthroplasty. csDMARDs, conventional synthetic disease-modifying anti-rheumatic
drugs38 (Reproduced with permission).

readmission in a study of patients with RA undergoing hip infection risk and little data to support its use, the ACR/
fracture, abdominopelvic or major cardiac surgery.31 AAHKS guideline recommends giving only the usual daily
These data suggest that minimising glucocorticoids in dose of glucocorticoids on the day of surgery for adults
the months before elective surgery may improve outcomes receiving chronic steroids for their rheumatic condition
and that delaying elective surgery may be appropriate in at the time of elective TKA and THA.26
some situations, especially for patients receiving high
doses of glucocorticoids.
Long-term glucocorticoid therapy cannot be abruptly CONCLUSION
stopped during a physiologic stress such as surgery, how- Patients with RA continue to undergo and benefit from
ever, out of concern for adrenal insufficiency causing THA and TKA, and the majority receive csDMARDs, glu-
hypotension and even death. The question for clinicians cocorticoids or targeted therapies at the time of surgery.
is whether to administer supraphysiologic doses (‘stress A general approach to perioperative management before
dose steroids’) at the time of surgery to prevent adrenal elective THA and TKA is summarised in figure 4. Current
insufficiency or continue the usual dose; however, stress practice supports continuing csDMARDs through sur-
dosing, or supraphysiologic doses meant to mimic the gery. Glucocorticoids should be tapered to at least less
response to stress, remains prevalent.55 There are little than 15 mg prior to surgery, and lower if possible. At the
data to guide the need for stress dosing. In a systematic time of surgery, glucocorticoids should be continued at
review that included seven observational cohorts and two their presurgical dose rather than using ‘stress doses’.
randomised controlled trials and included 315 patients While observational studies have not shown clear differ-
and 389 operations, there was no haemodynamic differ- ences in the rate of postoperative infection in patients
ence between those receiving stress dosing compared who stop biologics before surgery, concerns remain given
with those who did not, and measuring cortisol levels known risks associated with these therapies; performing
was not helpful.55 Given the potential for an increase in surgery at the end of the biologic dosing cycle and

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restarting at approximately 2 weeks after the wound has mortality risk for the medicare population. J Arthroplasty
2018;33:3238–45.
closed achieved consensus support from the guideline 13 Chen J, Cui Y, Li X, et al. Risk factors for deep infection after total knee
development panel of the ACR/AAHKS. arthroplasty: a meta-analysis. Arch Orthop Trauma Surg
2013;133:675–87.
14 Schrama JC, Fenstad AM, Dale H, et al. Increased risk of revision for
Funding The authors report grants from Bristol-Myers Squibb, personal fees from infection in rheumatoid arthritis patients with total hip replacements.
AbbVie, Expert witness testimony, grants and personal fees from Novartis, and Acta Orthop 2015;86:469–76.
personal fees from American College of Rheumatology, outside the submitted work. 15 Beam E, Osmon D. Prosthetic joint infection update. Infect Dis Clin
North Am 2018;32:843–59.
Competing interests SMG has consulted for Novartis and UCB, and has research 16 Ravi B, Croxford R, Austin PC, et al. Increased surgeon experience with
funding from Novartis, Pfizer and Horizon Pharma. MDG has consulted for AbbVie rheumatoid arthritis reduces the risk of complications following total
and has research funds from Bristol Meyers Squibb. joint arthroplasty. Arthritis Rheumatol 2014;66:488–96.
17 Goodman SM, Nocon AA, Selemon NA, et al. Increased
Patient consent for publication Not required. Staphylococcus aureus nasal carriage rates in rheumatoid arthritis
patients on biologic therapy. J Arthroplasty 2019;34:954–8.
Disclaimer The views expressed in the submitted article are of the authors’ own 18 Maoz G, Maoz G, Phillips M, et al. The Otto Aufranc award: modifiable
and are not an official position of the institution. versus nonmodifiable risk factors for infection after hip arthroplasty.
Clin Orthop Relat Res 2015;473:453–9.
Provenance and peer review Commissioned; externally peer reviewed. 19 Kuettel D, Primdahl J, Weber U, et al. Pain and self-reported swollen
Supplemental material This content has been supplied by the author(s). It has not joints are main drivers of patient-reported flares in rheumatoid arthritis.
been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer- Results from a 12-months’ observational study. J Rheumatol 2019;
jrheum.190760.
reviewed. Any opinions or recommendations discussed are solely those of the author(s)
20 Myasoedova E, Crowson C, Giblon R, et al. Optimization of flare
and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from management in patients with rheumatoid arthritis: results of
any reliance placed on the content. Where the content includes any translated material, a randomized controlled trial. Clin Rheumatol 2019;38:3025–32.
BMJ does not warrant the accuracy and reliability of the translations (including but not 21 Smolen JS, Pedersen R, Jones H, et al. Impact of flare on radiographic
limited to local regulations, clinical guidelines, terminology, drug names and drug progression after etanercept continuation, tapering or withdrawal in
dosages), and is not responsible for any error and/or omissions arising from translation patients with rheumatoid arthritis. Rheumatology 2020;59:153–64.
22 McWilliams DF, Rahman S, James RJE, et al. Disease activity flares and
and adaptation or otherwise.
pain flares in an early rheumatoid arthritis inception cohort;
Open access This is an open access article distributed in accordance with the characteristics, antecedents and sequelae. BMC Rheumatol
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which 2019;3:49.
permits others to distribute, remix, adapt, build upon this work non-commercially, 23 Hewlett S, Sanderson T, May J, et al. ‘I’m hurting, I want to kill myself’:
and license their derivative works on different terms, provided the original work is rheumatoid arthritis flare is more than a high joint count-an international
properly cited, appropriate credit is given, any changes made indicated, and the use patient perspective on flare where medical help is sought.
is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. Rheumatology 2012;51:69–76.
24 Goodman SM, Mirza SZ, DiCarlo EF, et al. Rheumatoid arthritis flares
ORCID iDs after total hip and total knee arthroplasty: outcomes at one year.
Arthritis Care Res (Hoboken) 2020.
Susan M Goodman MD http://orcid.org/0000-0003-1197-7864
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