The present study is the first to survey rheumatologists and orthopedic surgeons about peri-arthroscopic management of immunosuppressive medications in patients with rheumatic disease. Our overall findings demonstrate general agreement between the two groups of physicians in peri-arthroscopic immunosuppression management, for both lower-risk and higher-risk arthroscopies. While the management paradigm to date has focused on balancing the risk of infection with the risk of disease flares, our findings suggest that procedural complexity and associated infection risks are key management considerations for the physicians.
In lower-risk arthroscopies, rheumatologists are more in favor than orthopedists of continuing the various csDMARDs perioperatively. That said, rheumatologists were more closely aligned with orthopedists regarding the continued use of biologics and JAK inhibitors in lower-risk arthroscopy. These preferences mirror recent ACR/AAHKS recommendations (for total joint arthroplasty) and suggest providers are more likely to follow these guidelines in lower-risk arthroscopic procedures (like meniscectomies) with a lower overall postoperative complication rate from all etiologies (2.8%), including not only infections but also surgical, anesthetic, and medical complications, and pulmonary emboli.(9) Additionally, where the risk of infection is low, physicians must consider the risk of inducing flares of autoimmune disease – and post-operative complications – from holding immunosuppression combined with the stress of surgery, especially in patients with higher baseline disease levels.(4, 10) This is a balancing act that more likely errs on the side of more immunosuppression to prevent flares in these arthroscopies.
In higher-risk arthroscopies like ACL reconstructions with higher overall complication rates (9.0%)(9), orthopedic surgeons prefer risk-reduction and holding of all medications but rheumatologists favor continuing csDMARDs and holding the other categories of immunosuppressive medication. While orthopedic surgeon preferences for arthroscopy are at odds with ACR/AAHKS arthroplasty guidelines which recommend continuation of csDMARDs and holding of other classes of immunosuppressive medications, they align with studies in the orthopedic literature that highlight significant variation in the incidence of infection and overall complications after arthroscopy. Furthermore, this variation may be attributable to procedural complexity and technique.(6, 9, 11, 12) Results of a study analyzing complication rates after orthopedic surgeries reported in the American Board of Orthopedic Surgery Database showed an increase in complication rates with rising procedural complexity from meniscectomy (2.8%) to ACL reconstruction (9.0%). In a retrospective review of a large insurance database, Yeranosian et al reported a higher rate of infections after procedures like rotator cuff repairs, possibly because they require implant placement in the subacromial space which has direct communication with the skin.(12) Given larger risks for infection inherent to procedure type with these more invasive and complicated arthroscopies, cessation of immunosuppressive medications perioperatively may be favored to mitigate risk if the risk of a resulting disease flare is low enough. However, with regards to the timing of holding and restarting medications perioperatively, our results show no significant differences when comparing higher-risk to lower-risk arthroscopic procedures.
Glucocorticoid management was not included in the current study due significant controversy in management. Historically, management of glucocorticoids was driven by the stress dose paradigm, adopted in reaction to adrenal insufficiency related deaths in patients whose long term glucocorticoids were discontinued preoperatively.(13) However, recent debate in the literature suggests that continuing patients’ baseline daily doses may be enough to prevent adrenal insufficiency.(14–16) In addition, guidelines recommend the opposite of supraphysiologic doses – tapering of steroids to < 20 mg/day if possible due to infection risk.(5) Investigators have also suggested that recency of exposure may play an equally important role as the dose, including Baker et al who showed a dose-dependent risk of postoperative infection starts even lower doses of glucocorticoids (5–10 mg).(8) While the study averaged doses over 90 days and was thus limited in knowledge of whether patients received chronic low dose glucocorticoids or acute preop or postop high dose glucocorticoids, authors suggest that recent glucocorticoid exposure likely has a larger effect on postoperative complications than cumulative exposure. Further investigation is needed to determine whether the current timing of perioperative holding and restarting of glucocorticoids is optimal and to what extent procedural complexity should impact perioperative medication timing.
The 2017 ACR/AAHKS guidelines for arthroplasties recommend that 1) csDMARDS (hydroxychloroquine, sulfasalazine, methotrexate, leflunomide) should be continued perioperatively, 2) biologics and targeted therapies should be stopped one dosing interval before surgery, 3) JAK inhibitors like tofacitinib should be stopped for seven days before surgery, 4) glucocorticoids should be tapered to < 20 mg/day, 5) medications should not be restarted until at least 14 days after surgery in order to ensure proper wound healing and avoid infection. Recent studies in the orthopedic literature, however, have challenged this status quo. Ibrahim et al’s 2019 meta-analysis found significantly increased risk of infection in rheumatoid arthritis (RA) patients who continued methotrexate therapy at the time of total joint arthroplasty, in contrast to several previous studies suggesting a lower frequency of infections. It remains unknown whether these risks remain in higher-risk surgeries including total joint arthroplasties and more involved arthroscopic procedures like ACL reconstructions compared to lower-risk arthroscopies. In a cohort study of Medicare and MarketScan data investigating postoperative complications in RA patients exposed to biologics and glucocorticoids before total joint arthroplasty, Baker et al showed that various biologic medications all have similar infection risks, in contrast to previous reports in the literature. As most patients included in the study were chronically on biologic therapy and likely had well-controlled RA, the authors suggest that the differences between various biologics may not be present among patients on chronic therapy due to well-controlled disease. Given that disease control may impact postoperative complication risk and that infection risk with biologics is greatest in the months after initiation, the extent to which poorly controlled disease drives risk compared to chronic biologic therapy exposure itself remains to be investigated.
There were some limitations of the current study. While this was a diverse multicenter study within one network, which increases internal validity of the findings, it limits the generalizability of the findings since physicians in other networks may adjust their patients’ immunosuppression differently around the time of arthroscopy. In addition, we used two separate surveys to target questions to rheumatologists and orthopedists, ultimately preventing statistical analyses beyond descriptive statistics to compare the two groups. However, this allowed for appropriate illustration of the groups’ differences in perspective given their respective emphasis on medical and surgical considerations. Finally, the survey focused on patients with disease controlled on baseline immunosuppression at the time of surgery, and rarer cases of disease flaring at baseline near the time of surgery were not addressed by this survey as they would require more case specific discussions.