Methotrexate Should Be Continued Through Elective Surgery
For adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or juvenile idiopathic arthritis on methotrexate undergoing elective surgery, continue the usual dosing through the perioperative period without interruption 1.
Evidence-Based Recommendation
The 2022 ACR/AAHKS guideline provides a conditional recommendation (based on low to moderate quality evidence) to continue methotrexate at the usual dosing schedule through surgery for patients with inflammatory arthritis undergoing total hip or knee arthroplasty 1. This recommendation extends to other elective surgical procedures based on the same mechanistic rationale.
Key Supporting Evidence
Continuation does not increase infection risk: Low-certainty evidence from randomized trials shows perioperative continuation of methotrexate may have little or no effect on postoperative infections (RR 1.00,95% CI 0.31-3.19) 2
Discontinuation significantly increases flare risk: Stopping methotrexate perioperatively dramatically increases disease flare risk (RR 32.99,95% CI 4.54-239.53), with 36% of patients experiencing flares when discontinued versus 0% when continued 2
No increase in wound complications: Multiple observational studies confirm methotrexate continuation is not associated with evident increases in early postoperative complications 3
Practical Management Algorithm
Continue Methotrexate If:
- Patient is on ≤15 mg/week
- Disease is well-controlled
- Standard surgical risk profile
Consider Dose Reduction (Not Discontinuation) If:
- Patient is on >15 mg/week (reduce to ≤15 mg/week) 4
- High infection risk procedure (e.g., prosthetic joint surgery with prior infection history)
Timing of Resumption (If Held):
- Restart when wound shows evidence of healing
- Sutures/staples are removed
- No significant swelling, erythema, or drainage present
- No ongoing non-surgical site infection
- Typically ~14 days postoperatively 1
Critical Caveats
Do not confuse methotrexate management with biologic DMARDs: While methotrexate should be continued, biologic agents (TNF inhibitors, rituximab, etc.) should be withheld prior to surgery and the procedure scheduled after the next dose is due 1. This is a common source of confusion.
Glucocorticoid management is separate: Patients on chronic glucocorticoids should continue their current daily dose rather than receiving supraphysiologic stress doses 1. The glucocorticoid dose should ideally be reduced to <10 mg/day prednisone equivalent 2-3 months before elective surgery if possible 4.
High-dose methotrexate for oncologic indications: The FDA labeling discusses high-dose methotrexate (12-15 g/m²) for osteosarcoma with leucovorin rescue 5. This is entirely distinct from low-dose methotrexate for rheumatic disease (typically 7.5-25 mg/week) and requires different perioperative considerations including renal function monitoring and delayed wound healing risk.
Strength of Recommendation
While the ACR guideline labels this as "conditional" due to evidence quality, the risk-benefit analysis strongly favors continuation: the substantial flare risk (36% vs 0%) with discontinuation far outweighs any theoretical infection risk, which was not demonstrated in available trials 2. The observational literature consistently supports this approach across multiple surgical contexts 3, 6.
The default approach should be continuation unless specific high-risk features mandate individualized assessment (e.g., active infection, severely immunocompromised state, or doses >15 mg/week requiring reduction).