Can a patient with well‑controlled rheumatoid arthritis on weekly methotrexate safely continue the medication during anterior cervical discectomy and fusion (ACDF) surgery?

Can Methotrexate Be Continued for ACDF Surgery in Well-Controlled RA?

Yes, methotrexate should be continued through ACDF surgery in patients with well-controlled rheumatoid arthritis, following the same perioperative management principles established for other orthopedic procedures.

Guideline-Based Recommendation

The 2022 ACR/AAHKS guideline for perioperative management of antirheumatic medications provides a conditional recommendation to continue usual dosing of methotrexate through surgery for patients with RA undergoing elective orthopedic procedures 1. While this guideline specifically addresses total hip and knee arthroplasty, the underlying principles apply to other orthopedic surgeries including ACDF, as the biological mechanisms affecting wound healing and infection risk are similar across orthopedic procedures.

Key Evidence Supporting Continuation

Benefits of Continuation:

• Disease control maintenance: Stopping methotrexate leads to increased risk of RA flares in the perioperative period, which can compromise rehabilitation and functional recovery 2
• No increased infection risk: Multiple systematic reviews demonstrate that continuing low-dose methotrexate (typically 7.5-25 mg/week) does not significantly increase postoperative infection rates 3, 2
• Better overall outcomes: Patients maintaining methotrexate therapy experience better disease control without evident increases in wound complications 4

Dosing Context:

The typical RA maintenance dose (7.5-25 mg/week orally) is substantially lower than the high-dose regimens used in oncology (12-15 g/m² IV), making the safety profile more favorable for perioperative continuation 5.

Important Caveats and Risk Stratification

Consider Withholding Methotrexate If:

• History of severe or recurrent infections 1
• Prior prosthetic joint infection 1
• Active infection present
• Significant immunocompromise from other causes
• Poor nutritional status or baseline wound healing concerns

Contradictory Evidence to Acknowledge:

One 2026 propensity-matched study specifically examining ACDF outcomes found that DMARD therapy (including methotrexate) was associated with higher 90-day readmission (4.3% vs 2.0%) and reoperation rates (4.1% vs 2.0%, and 8.3% vs 4.1% at 2 years) 6. However, this study has significant limitations:

• It grouped all DMARDs together rather than analyzing methotrexate specifically
• It contradicts the larger body of evidence from systematic reviews and RCTs
• The absolute risk differences remain small
• The study design cannot definitively establish causation

An older 1991 study suggested increased complications when methotrexate was continued within 4 weeks of surgery 7, but this has been contradicted by subsequent higher-quality evidence including randomized trials 2.

Practical Management Algorithm

Standard Approach (Low-Risk Patient):

1. Continue methotrexate at usual weekly dose through surgery
2. Resume immediately postoperatively once oral intake tolerated
3. Monitor wound healing at standard intervals

Modified Approach (High-Risk Patient):

1. Withhold the dose immediately before surgery (skip one weekly dose)
2. Resume 10-14 days postoperatively once wound shows evidence of healing, sutures/staples are removed, and there is no significant swelling, erythema, drainage, or infection 1
3. Closer wound monitoring in early postoperative period

Glucocorticoid Consideration:

If the patient is also taking chronic glucocorticoids for RA (common), continue the current daily dose rather than stress-dose supplementation 1. Note that chronic glucocorticoid exposure itself is associated with worse surgical outcomes independent of methotrexate 4.

Clinical Pitfalls to Avoid

• Do not confuse weekly dosing with daily dosing: Methotrexate for RA is dosed weekly, and accidental daily administration has caused fatal toxicity 5
• Do not extrapolate high-dose oncology data: The safety concerns and monitoring requirements for high-dose IV methotrexate do not apply to low-dose oral RA therapy 5
• Do not stop methotrexate reflexively: The risk of disease flare may outweigh theoretical infection concerns in well-controlled patients 3, 2

Monitoring Recommendations

Standard postoperative wound monitoring is sufficient. No additional laboratory monitoring beyond routine RA management is required for the perioperative period unless complications arise 4.

The decision ultimately balances infection/wound healing risk against disease flare risk, with current high-quality evidence favoring continuation in most patients with well-controlled RA undergoing ACDF 1, 4, 2.