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duration of immunosuppression after the drug is withheld, although indirect translational data suggest that host defense returns to normal at 7 days. 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). 4. Severe SLE (as defined in Table 1) Continue the current dose of methotrexate, mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus through the surgical period in all patients undergoing THA or TKA (Table 2). There is a great deal of uncertainty and little published experience regarding risks associated with perioperative medication management in patients with severe SLE. There is, however, indirect evidence concerning organ transplant patients who continue anti-rejection therapy through the surgical period (99,100). The caveat to this analogy is that the time course of organ rejection after withholding immunosuppressant medication may be different from the time to SLE flare after withholding medications. These considerations led to the recommendation to continue the current dose of methotrexate, mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus through the surgical period in all patients with severe SLE. Nevertheless, the Panel felt that decisions regarding elective surgery in patients with severe SLE should be made on an individual basis with the patient’s rheumatologist. 5. Not-severe SLE (as defined in Table 1) Withhold the current dose of mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus 1 week prior to surgery in all patients undergoing THA or TKA (Table 2). For patients with not-severe SLE, the time course to flares after withholding medications is not known, while there is a known infection risk associated with these medications. The Panel felt that careful monitoring of the patient after surgery would permit restarting the medications prior to clinical flares in patients with not-severe SLE, for whom the morbidity of infection might outweigh the risk of a flare. These medications can be withheld 1 week prior to surgery, permitting some return of normal immune function, and restarted at 3–5 days after surgery in the absence of wound healing complications or infection at the surgical site or elsewhere. There are multiple mechanisms postulated for immunosuppression with these medications, including leukopenia, interference with T cell costimulatory signaling, and blocking the de novo pathway of purine synthesis, with different time courses for onset and reversal (101,102). 6. RA, SpA including AS and PsA, JIA, or SLE Restart biologic therapy in patients for whom biologic therapy was withheld prior to undergoing THA or TKA once the wound shows evidence of healing (typically ~14 days), all sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no clinical evidence of non–surgical site infections (Table 2). The decision to restart antirheumatic therapy can be based on evaluation of the patient’s wound status and clinical judgment for absence of surgical and non–surgical site infections; wound closure is typically reached by 14 days. Therefore, biologic therapy can be restarted once the wound shows evidence of healing (typically ;14 days), all sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no clinical evidence of ACR/AAHKS Guideline for Perioperative Management 1117 Table 2. Recommendations for perioperative management of antirheumatic drug therapy in patients with rheumatic diseases undergoing elective THA or TKA* Recommendation/strength of recommendation (bold indicates conditional) Level of evidence RA, SpA including AS and PsA, JIA, or SLE: Continue the current dose of methotrexate, leflunomide, hydroxychloroquine, and/or sulfasalazine (nonbiologic DMARDs) for patients undergoing elective THA or TKA. RCTs of continuing vs. discontinuing DMARDs at the time of surgery revealed that the risk of infections was not increased, but in fact decreased, when DMARDs were continued, with an RR of 0.39 (95% CI 0.17–0.91) (37,38). Evidence indicates a low infection risk with these DMARDs in settings other than THA and TKA (39). Disease flares after surgery occur frequently, and continuing DMARDs decreases the risk (RR 0.06 [95% CI 0.0–1.10]) (37,40), yet flares were significantly less important than infection for the Patient Panel. Low to moderate RA, SpA including AS and PsA, JIA, or SLE: Withhold all current biologic agents (see Figure 1) prior to surgery in patients undergoing elective THA or TKA, and plan the surgery at the end of the dosing cycle for that specific medication. RCTs (nonsurgical) demonstrated an increase in infection risk associated with use of all biologic agents (41–87). Avoiding infection was significantly more important to patients than flares for patients with RA and JIA. Meta-analysis and network meta-analysis revealed that infection risk for biologic agents is strongly associated with high-dose therapy and may not be associated with low-dose biologic agents (42). Serum half-life may not correspond to the duration of the immune-suppressant effect, so the dosing cycle was chosen as more relevant in determining the withholding interval (88–91). Until further studies have clarified and established
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