In an adult rheumatoid arthritis patient undergoing elective surgery, how should conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs be managed perioperatively?

Perioperative DMARD Management in Rheumatoid Arthritis Patients Undergoing Elective Surgery

Continue conventional synthetic DMARDs (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine) through surgery without interruption, withhold all biologic DMARDs timing surgery at the end of the dosing cycle, and withhold targeted synthetic DMARDs (JAK inhibitors) for at least 3-7 days preoperatively. 1

Conventional Synthetic DMARDs (csDMARDs)

Continue methotrexate, leflunomide, hydroxychloroquine, and sulfasalazine at current doses throughout the perioperative period without any interruption. 1

• Continuing these medications actually reduces infection risk (RR 0.39,95% CI 0.17-0.91) compared to stopping them, contrary to common assumptions 1
• Disease flares are markedly reduced when csDMARDs are continued (RR 0.06,95% CI 0.0-1.10) 1
• This recommendation applies to all elective surgeries, not just joint replacements, though the strongest evidence comes from total hip and knee arthroplasty 1, 2
• Patients should take their usual morning dose on the day of surgery and resume immediately postoperatively once oral intake is tolerated 2

Common Pitfall to Avoid

Do not reflexively stop all immunosuppressive medications preoperatively—csDMARDs are protective against both infection and flares when continued 1, 2

Biologic DMARDs (bDMARDs)

Withhold all biologic agents prior to surgery and schedule the procedure at the time when the next dose would be due (end of dosing cycle). 1

Timing Algorithm by Specific Agent

• TNF inhibitors dosed every 2 weeks (adalimumab, certolizumab): Schedule surgery in week 3 1
• TNF inhibitors dosed every 4 weeks (golimumab subcutaneous): Schedule surgery in week 5 1
• TNF inhibitors dosed every 8 weeks (infliximab, golimumab IV): Schedule surgery in week 9 (first week after missed dose) 1
• Rituximab dosed every 6 months: Schedule surgery in month 7 (first week after missed dose) 1
• Abatacept, tocilizumab, sarilumab: Follow same principle—schedule at end of dosing cycle 1

Rationale

Biologic agents increase serious infection risk with most risk ratios approximately 1.5-fold (range 0.61-8.87), and RA patients undergoing joint replacement have nearly 2-fold increased baseline infection risk 1, 3

Restarting Biologics Postoperatively

Resume biologic therapy approximately 14 days after surgery once all of the following criteria are met: 1

• Wound shows evidence of healing
• All sutures/staples are removed
• No significant swelling, erythema, or drainage present
• No clinical evidence of surgical site or non-surgical site infection 1, 3

Critical Caveat

Do not restart biologics prematurely before adequate wound healing, as this increases infection risk, but also do not continue withholding indefinitely after appropriate healing, as this increases flare risk without reducing infection risk 3

Targeted Synthetic DMARDs (tsDMARDs)

Withhold JAK inhibitors (tofacitinib, baricitinib, upadacitinib) for at least 3-7 days prior to surgery. 1

• The 2022 ACR guideline recommends at least 3 days for all JAK inhibitors 1
• The 2017 ACR guideline recommended 7 days for tofacitinib specifically 1
• JAK inhibitors increase serious infection risk (incidence rate 2.91,95% CI 2.27-3.74) and all infections (RR 5.7,95% CI 1.8-18.1) 1
• Despite extremely short serum half-lives, the duration of immunosuppression after withholding is not well-characterized 1

Restart JAK inhibitors 3-5 days postoperatively in the absence of wound healing complications or infection. 1

Practical Consideration

Use the more conservative 7-day preoperative withholding period for higher-risk surgeries or patients with additional infection risk factors 1, 4

Special Considerations for Systemic Lupus Erythematosus (SLE)

Non-Severe SLE

Withhold mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus, and mizoribine 1 week prior to surgery. 1

Withhold belimumab and rituximab prior to surgery, timing at end of dosing cycle. 1

Severe SLE

Continue mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus, mizoribine, anifrolumab, and voclosporin through surgery without interruption. 1

Continue belimumab and plan surgery in the last month of rituximab dosing cycle. 1

• The distinction is critical: severe SLE patients face increased risk of life-threatening flares that outweighs infection risk 1, 4
• Patients with active or severe SLE have higher baseline risk for adverse surgical events 1

Evidence Quality and Strength

All recommendations are conditional due to low-to-moderate quality evidence, meaning they apply to most patients but require shared decision-making and may not apply to all clinical scenarios 1

• No randomized controlled trials exist specifically for perioperative DMARD management in surgical patients 1
• Evidence for csDMARDs comes from RCTs showing benefit when continued 1
• Evidence for biologics is indirect, derived from non-surgical RCTs showing increased infection risk 1
• The 2022 ACR/AAHKS guideline represents the most current authoritative guidance 1

Algorithmic Summary

1. Identify medication class: conventional synthetic, biologic, or targeted synthetic DMARD
2. For csDMARDs: Continue without interruption through surgery 1
3. For biologics: Calculate when next dose is due, schedule surgery at that time, restart at ~14 days if wound healed 1
4. For JAK inhibitors: Stop 3-7 days preoperatively, restart 3-5 days postoperatively if no complications 1
5. For SLE patients: Determine disease severity—continue immunosuppressants if severe, withhold if not severe 1

Scope and Limitations

These recommendations are derived primarily from elective total hip and knee arthroplasty data 1

The ACR explicitly cautions against extrapolating to other surgical procedures until further data are available, though the principles are commonly applied in clinical practice 1, 5