In an adult patient with rheumatoid arthritis newly diagnosed with gallbladder carcinoma, what is the optimal treatment strategy and how should the rheumatoid arthritis medications be managed perioperatively?

Management of Rheumatoid Arthritis Medications in Gallbladder Cancer Treatment

For an adult patient with rheumatoid arthritis newly diagnosed with gallbladder carcinoma requiring surgery, continue conventional DMARDs (methotrexate, sulfasalazine, leflunomide, hydroxychloroquine) through the perioperative period, withhold all biologic agents at the end of their dosing cycle before surgery, and maintain glucocorticoids at the current daily dose without stress-dose supplementation if ≤20 mg/day prednisone equivalent. 1

Surgical Treatment for Gallbladder Cancer

• Surgery remains the only curative option for gallbladder cancer, with treatment ranging from simple cholecystectomy for T1a disease to extended cholecystectomy (wedge resection of GB bed or segmentectomy IVb/V plus hepatoduodenal ligament lymphadenectomy) for T2 or higher stages 2, 3
• Most patients are diagnosed incidentally during cholecystectomy for presumed benign disease, making perioperative medication management planning critical 4

Perioperative Management of RA Medications

Conventional DMARDs (Continue)

• Continue methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine throughout the perioperative period without interruption 1
• Evidence from RCTs demonstrates that continuing DMARDs actually decreases infection risk (RR 0.39,95% CI 0.17-0.91) compared to withholding them 1
• These medications can be safely restarted immediately when oral intake resumes postoperatively given their 1-2 hour elimination half-life 1

Biologic Agents (Withhold)

• Withhold all biologic DMARDs (TNF inhibitors, IL-6 inhibitors, IL-17 inhibitors, IL-23 inhibitors, abatacept, rituximab) and schedule surgery at the end of the dosing cycle for each specific medication 1
• For example: adalimumab (dosed every 2 weeks) should have surgery scheduled in week 3; infliximab (dosed every 8 weeks) should have surgery in week 9; rituximab (dosed every 6 months) should have surgery in month 7 1
• Meta-analyses demonstrate increased infection risk with biologic agents in non-surgical populations, particularly at high doses, making infection prevention the priority over flare risk 1
• Restart biologic agents 14 days postoperatively if wound healing is appropriate and no signs of infection are present 1

JAK Inhibitors (Withhold)

• Withhold tofacitinib, baricitinib, and upadacitinib for at least 7 days prior to surgery 1
• Evidence shows increased serious infection risk with tofacitinib (incidence rate 2.91,95% CI 2.27-3.74) despite its short serum half-life 1
• Restart JAK inhibitors 14 days postoperatively if wound healing is appropriate 1

Glucocorticoids (Continue at Current Dose)

• Continue the patient's current daily glucocorticoid dose throughout the perioperative period rather than administering supraphysiologic "stress doses" 1, 5
• The CDC defines 20 mg/day prednisone for ≥2 weeks as the immunosuppression threshold; optimal surgical candidates should be on <20 mg/day when possible 1, 6, 5
• Patients on ≥15-20 mg/day prednisone have significantly increased risk of postoperative infectious complications (OR 1.68,95% CI 1.24-2.28) 1, 6
• If the patient is on >20 mg/day, attempt to taper by 5 mg every 3-5 days preoperatively to reach <20 mg/day before elective surgery 6

Critical Perioperative Considerations

Infection Risk Prioritization

• Patients with RA have a 50% increased risk of periprosthetic joint infection compared to osteoarthritis patients, and this elevated infection risk applies to all major surgeries 1
• Patient panels consistently prioritize avoiding infection over preventing disease flares, even though flares occur in >60% of patients postoperatively 1
• The rationale for withholding biologics is based on indirect evidence showing increased infection risk in non-surgical populations, applied conservatively to the surgical setting 1

Disease Activity Optimization

• Ideally, RA disease activity should be well-controlled before elective surgery, as active disease itself is a non-modifiable risk factor for adverse outcomes 1
• If disease is poorly controlled, consider delaying elective surgery to optimize DMARD therapy, though this may not be feasible with gallbladder cancer requiring timely intervention 1

Postoperative Medication Resumption

• Conventional DMARDs can be restarted immediately when oral intake resumes 1
• Biologic agents and JAK inhibitors should be withheld for 14 days postoperatively, then restarted if wound healing is appropriate and no infection is present 1
• Patients with postoperative complications (infection, delayed wound healing) may require longer delays in restarting immunosuppressive therapy 1

Important Caveats

• These recommendations are based on low-quality evidence from orthopedic surgery literature (primarily total joint arthroplasty), as no high-quality RCTs exist for perioperative medication management in major abdominal surgery 1
• The principles may be extrapolated to gallbladder cancer surgery, though the evidence base specifically addresses joint replacement procedures 1
• Individual patient factors such as prior severe infections, prior surgical site infections, or severe/organ-threatening RA may warrant deviation from these recommendations in consultation with rheumatology 1
• Gallbladder cancer prognosis is poor even with optimal surgical management, so balancing oncologic outcomes with infection risk requires multidisciplinary discussion 4, 7, 3