What are the recommended timing and criteria for holding methotrexate before an elective operation?

Methotrexate Should Be Continued Through Elective Surgery

For patients with rheumatoid arthritis and other rheumatic diseases undergoing elective orthopedic surgery, methotrexate should be continued at the current dose throughout the perioperative period without interruption. 1

Evidence-Based Rationale

The American College of Rheumatology's most recent guidelines (2022) provide a conditional recommendation to continue methotrexate through elective orthopedic procedures based on moderate-quality evidence showing:

• Decreased infection risk when methotrexate is continued (RR 0.39,95% CI 0.17-0.91) 1
• Reduced disease flare risk (RR 0.06,95% CI 0.0-1.10) 1
• No increase in surgical complications or poor wound healing 2, 3

This recommendation applies to total hip arthroplasty, total knee arthroplasty, spine surgery, and other major orthopedic procedures. 1, 4

Application to Different Surgical Contexts

Elective Orthopedic Surgery

• Continue methotrexate at the usual weekly dose without any perioperative interruption 5, 1
• This includes hip, knee, spine, and other orthopedic procedures 1, 4

Inflammatory Bowel Disease Surgery

• Continue methotrexate through the perioperative period, as the elimination half-life is only 1-2 hours and stopping provides no measurable benefit 1

General Elective Surgery

• The same principles apply: continue methotrexate for most patients undergoing elective procedures 1

When Methotrexate MUST Be Held

There are specific clinical scenarios where methotrexate should be temporarily discontinued:

Acute Infection

• Stop methotrexate if the patient develops an infection requiring antibiotics 6
• Hold until the patient recovers and completes the antibiotic course 6

Renal Dysfunction

• Avoid methotrexate if creatinine clearance <20 mL/min 6
• Reduce dose by 50% if creatinine clearance 20-50 mL/min 6
• Ensure creatinine clearance >60 mL/min before elective surgery for optimal safety 1

Hepatic Dysfunction

• Stop if transaminases exceed 3 times the upper limit of normal 5
• Hold if ALT/AST >2 times upper limit of normal in acute illness 6

Bone Marrow Suppression

• Withhold if total white cells <3.5×10^9/L or neutrophils <2×10^9/L 6

Acute Hospitalization

• Temporarily discontinue during acute illness or hospitalization, particularly when receiving multiple interacting medications (antibiotics, NSAIDs) 6

Postoperative Management

Uncomplicated Surgery

• Resume methotrexate immediately when oral intake recommences 1, 4
• No waiting period is necessary if surgery was uncomplicated 1

If Methotrexate Was Held

• Restart once the wound shows evidence of healing (typically ~14 days) 1, 4
• Specific criteria: sutures/staples removed, no significant swelling/erythema/drainage, no clinical evidence of infection 1, 4

Common Pitfalls to Avoid

Outdated Practice Patterns

The older literature from the 1990s suggested holding methotrexate for 2 weeks perioperatively due to theoretical infection concerns. 7 This practice is now contradicted by higher-quality evidence showing that continuation is safer. 1, 2

Confusing Methotrexate with Biologics

• Biologic agents (TNF inhibitors, etc.) should be held and surgery planned at the end of the dosing cycle 1, 4
• Methotrexate follows different rules and should be continued 1

Disease Flare Risk

Discontinuing methotrexate increases the risk of disease flares (8-14% flare rate when stopped vs. 0-4% when continued). 2, 8 The multinational consensus strongly supports continuation to maintain disease control. 5

Drug Interactions

Be vigilant about postoperative medications that increase methotrexate toxicity risk, including penicillins, NSAIDs, proton pump inhibitors, and tetracyclines. 6 If these are required for infection treatment, temporarily hold methotrexate. 6

Strength of Evidence

The recommendation to continue methotrexate is supported by:

• Level 1b evidence from prospective randomized controlled trials 2
• Long-term follow-up data showing no late deep infections 3
• Multinational expert consensus 5
• Current American College of Rheumatology guidelines 1

The evidence consistently demonstrates that continuing methotrexate is safer than stopping it, with lower infection rates and better disease control. 1, 2