What are the guidelines for managing methotrexate (MTX) treatment in patients undergoing surgery, particularly those with rheumatoid arthritis or other autoimmune disorders?

Methotrexate and Surgery

Continue methotrexate through the perioperative period for patients with rheumatoid arthritis and other rheumatic diseases undergoing elective orthopedic surgery. 1

Primary Recommendation for Elective Orthopedic Surgery

• The American College of Rheumatology (2017) conditionally recommends continuing the current dose of methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine for patients with RA, SpA (including AS and PsA), JIA, or SLE undergoing elective total hip or total knee arthroplasty. 1

• Randomized controlled trials demonstrate that continuing methotrexate actually decreases infection risk (RR 0.39,95% CI 0.17-0.91) compared to discontinuation. 1

• Continuing methotrexate also reduces the risk of disease flares (RR 0.06,95% CI 0.0-1.10), which is clinically significant even though patients rated infection prevention as more important than flare prevention. 1

• This recommendation is supported by multinational evidence-based guidelines (2009) stating that methotrexate can be safely continued in the perioperative period in RA patients undergoing elective orthopedic surgery. 1

Evidence Base

• The largest prospective randomized study (388 patients) showed that patients who continued methotrexate had only 2% infection/complication rates versus 15% in those who discontinued methotrexate and 10.5% in those not on methotrexate. 2

• Logistic regression analysis confirmed that methotrexate continuation did not increase complication rates, while other medications (penicillamine, indomethacin, cyclosporin, hydroxychloroquine, chloroquine, prednisolone) significantly increased surgical risk. 2

• Ten-year follow-up data show no evidence of late deep infections in patients who continued methotrexate perioperatively. 3

Application to Other Surgical Procedures

• For spine surgery and other major orthopedic procedures, the same principles apply: continue methotrexate for most patients, though individual risk factors (significant comorbidities, diabetes, immunocompromise) require case-by-case assessment. 4

• For inflammatory bowel disease patients, methotrexate can be continued during the perioperative period without adversely affecting postoperative outcomes, as the elimination half-life is only 1-2 hours, making immediate preoperative discontinuation ineffective. 5

When to Withhold Methotrexate

• Withhold biologic agents (but not methotrexate) prior to surgery, planning the procedure at the end of the dosing cycle for the specific biologic medication. 1

• Temporarily discontinue methotrexate during acute hospitalization for infection, particularly when patients require antibiotics or have acute illness. 5

• Stop methotrexate if postoperative infection develops requiring antibiotics; resume once infection resolves and antibiotic course is completed. 5, 6

Resuming Therapy After Surgery

• Resume methotrexate immediately when oral intake recommences after uncomplicated surgery. 5

• If methotrexate was held perioperatively, restart once the wound shows evidence of healing (typically ~14 days), all sutures/staples are removed, there is no significant swelling/erythema/drainage, and no clinical evidence of infection. 1

Critical Pitfalls to Avoid

• Do not routinely discontinue methotrexate based on outdated concerns from the 1990s about increased infection risk—current evidence demonstrates the opposite effect. 1, 2

• Avoid withholding methotrexate for 2 weeks perioperatively, as older literature suggesting this approach 7 has been superseded by higher-quality randomized controlled trials showing harm from discontinuation. 1, 2

• Monitor for disease flares if methotrexate is discontinued, as flares occurred in 8-14% of patients who stopped methotrexate versus 0% who continued it. 2

• Ensure adequate renal function before surgery (creatinine clearance >60 mL/min), as impaired renal function significantly increases methotrexate toxicity risk. 5

Special Monitoring Considerations

• If methotrexate was administered shortly before unplanned surgery or hospitalization, monitor complete blood count, liver function tests, and renal function closely for signs of toxicity (mucositis, fever, diarrhea, erythema, ulceration). 5

• Glucocorticoids should be continued at the current daily dose rather than administering supraphysiologic stress doses, as traditional stress-dose steroids lack strong evidence and may increase perioperative complications. 5