Combining Skyrizi and Imuran in Ulcerative Colitis
Yes, Skyrizi (risankizumab) can be combined with Imuran (azathioprine) for moderate to severe ulcerative colitis, though current evidence does not demonstrate superiority of this combination over risankizumab monotherapy, and the decision should weigh potential increased infection and malignancy risks against uncertain additional benefit.
Evidence for Combination Therapy
Established Combinations vs. IL-23 Inhibitor Combinations
Combination therapy is proven beneficial specifically for infliximab plus azathioprine, with the UC-SUCCESS trial demonstrating that infliximab/azathioprine achieved 39.7% corticosteroid-free remission at week 16 compared to 22.1% with infliximab alone (p=0.017) 1
The AGA 2024 guidelines address combination therapy questions (PICO questions 5-6) but focus on TNF antagonists and non-TNF biologics without specific recommendations for IL-23 inhibitors like risankizumab combined with immunomodulators 1
No randomized controlled trials have evaluated risankizumab in combination with azathioprine or other immunomodulators 2, 3
Rationale and Limitations
The primary rationale for combination therapy with TNF antagonists is reducing immunogenicity and anti-drug antibody formation, which leads to treatment failure 2, 3
IL-23 inhibitors like risankizumab may have inherently lower immunogenicity compared to TNF antagonists, potentially reducing the need for concomitant immunosuppression 4, 5
Combination therapy with biologics and immunomodulators increases toxicity risk, mainly infections and lymphoproliferative malignancies 2, 3
Clinical Decision Algorithm
When Combination May Be Considered:
Patients already on stable azathioprine therapy who require escalation to risankizumab - continuing azathioprine may be reasonable for at least 12 months to minimize any potential immunogenicity during the initiation phase 2
Patients with limited treatment options and prior biologic failures - where maximizing response rates justifies accepting increased toxicity risk 2
When Monotherapy Is Preferred:
Biologic-naïve patients starting risankizumab - the AGA strongly recommends risankizumab for moderate-to-severe UC with moderate to high certainty of evidence as monotherapy 1, 4
Patients at increased risk for infection or malignancy - where the uncertain benefit of combination does not justify known increased toxicity 2, 3
Risankizumab demonstrated 20.3% clinical remission at week 12 versus 6.2% with placebo as monotherapy, with maintenance remission rates of 40.2% (180 mg) and 37.6% (360 mg) at week 52 6
Safety Monitoring
If combining, monitor for opportunistic infections and consider limiting combination duration to 12 months, as most immunogenicity develops early in biologic treatment 2
Lower doses of immunosuppressives may reduce toxicity while maintaining efficacy in reducing immunogenicity, though this has not been specifically studied with risankizumab 2
Common Pitfalls
Avoid extrapolating SONIC and UC-SUCCESS trial results (infliximab + azathioprine) directly to risankizumab, as these findings may not apply to IL-23 inhibitors with different immunogenicity profiles 1, 2, 3
Do not assume combination therapy is automatically superior - the registration trials for vedolizumab and ustekinumab showed no superiority for combination therapy, and risankizumab trials were conducted as monotherapy 2