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differences in risk between biologic agents, there was insufficient evidence to support separating biologic agent management in the perioperative period (43–89). For SLE, there was paucity of data supporting perioperative benefit in SLE (93–95). A systematic review of rituximab vs. placebo (and occasionally vs. control treatment including nonbiologic DMARDs) in nonsurgical patients with RA and SLE revealed the risk of all serious adverse events with a range of RRs from 0.85 (95% CI 0.62–1.17) to 0.89 (95% CI 0.7–1.14) (59,92). Observational studies reveal that patients with SLE, particularly those with active or severe SLE, are at a higher risk for adverse events after surgery. Belimumab is indicated for use in not-severe SLE, which is not thought to increase perioperative risk (95,96). As an example, using this guideline, patients treated with rituximab every 6 months would schedule their surgery, when possible, at the week after the first withheld dose during month 7. Patients receiving belimumab, which is given every 4 weeks, would schedule their surgery during week 5. Patients treated with adalimumab, dosed at 2-week intervals, would plan their surgery in week 3, while patients treated with infliximab, when dosed every 8 weeks, would schedule their surgery in the week after the first withheld dose during week 9. Low RA, SpA including AS and PsA, or JIA: Withhold tofacitinib for at least 7 days prior to surgery in patients undergoing THA or TKA. Indirect evidence from systematic reviews and meta-analyses of tofacitinib vs. placebo (and occasionally vs. control treatment including nonbiologic DMARDs) in nonsurgical patients shows that the risk of serious infections was increased with tofacitinib with an incidence rate of 2.91 (95% CI 2.27–3.74) (97) and higher risk of all infections with an RR of 5.7 (95% CI 1.8–18.1) (48). Although this drug has an extremely short serum half-life, little is known about the duration of immunosuppression after the drug is withheld. Therefore, the Panel recognized that the recommendation for the duration of withholding may change in the future, as physician and patient experience with this drug grows (41,47,48,51,77,79,97,98). Low Severe SLE: Continue the current dose of mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus through the surgical period in all patients undergoing THA or TKA (see Figure 1). The Panel recognized that there is a great deal of uncertainty and little published experience regarding risks associated with perioperative medication management in patients with severe SLE. Indirect evidence with organ transplant patients supports continuing anti-rejection therapy without interruption at the time of surgery (99,100). Decisions regarding elective surgery in patients with severe SLE should be made on an individual basis with the patient’s rheumatologist. Low (continued) 1118 Goodman et al non–surgical site infections. There is no direct evidence regarding the optimal time to restart medication after surgery, but standard precautions for biologic agents warn against use in patients with an active infection or in highrisk settings, such as with an open wound. 7. RA, SpA including AS and PsA, or SLE Continue the current daily dose of glucocorticoids in adult patients with RA, SpA including AS and PsA, or SLE who are receiving glucocorticoids for their rheumatic condition and undergoing THA or TKA, rather than administering perioperative supra-physiologic glucocorticoid doses (so-called “stress dosing”) (Table 2). Hemodynamic instability/hypotension and infection risk were 2 specific areas of concern with regard to perioperative glucocorticoid dosing. Regarding hemodynamic instability, the recommendation to continue the current daily dose of glucocorticoids in adult patients who are receiving glucocorticoids, rather than administering perioperative supra-physiologic glucocorticoid doses (“stress dosing”), specifically refers to adults with RA, AS, PsA, or SLE who are receiving glucocorticoids (#16 mg/ day prednisone or equivalent) for their rheumatic condition; it does not refer to JIA patients receiving glucocorticoids who may have been treated with glucocorticoids during childhood developmental stages, or to patients receiving glucocorticoids to treat primary adrenal insufficiency or primary hypothalamic disease. Low-quality RCT evidence (rated down for indirectness due to varying glucocorticoid doses, heterogeneity of surgical procedures, and imprecision due to small numbers) and evidence from observational trials summarized in a systematic review suggested that there was no significant hemodynamic difference between those patients given their current daily glucocorticoid dose compared to those receiving “stress-dose steroids” (103). Regarding the infection risk, the Panel noted that the cutoff for immunosuppression according to the Centers for Disease Control and Prevention was 20 mg/day of prednisone for at least 2 weeks, in the context of risk Table 2. (Cont’d) Recommendation/strength of recommendation (bold indicates conditional) Level of evidence SLE (not severe): Withhold the current dose of mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus 1 week prior to surgery in all patients undergoing THA or TKA. The time course to flares in not-severe SLE is not known. The morbidity of prosthetic joint infection may be more
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