Treatment outcomes of prolonged induction or re-escalation dosing of upadacitinib in patients with inflammatory bowel disease.

Background: Proposed treatment algorithms favor the use of upadacitinib in medically refractory Crohn's disease (CD) and ulcerative colitis (UC). There has not yet been data published regarding efficacy of prolonged induction in CD or the efficacy of re-escalation to induction dosing in patients with either CD or UC. The aim of this study was to evaluate the real-world efficacy and safety of prolonged and/or re-escalation upadacitinib therapy in patients with inflammatory bowel disease (IBD) and prior inadequate response to standard upadacitinib treatment. Methods: This was a retrospective, dual-center study of the efficacy of prolonged induction or re-escalation of upadacitinib in patients with IBD with prior inadequate response to standard upadacitinib treatment. Results: Fifty-five patients met eligibility criteria. Thirty-nine (70.9%) persisted on upadacitinib therapy while 16 (29.1%) met the primary endpoint for upadacitinib failure. Of those that had comparative objective data, 62.5% had improvement in endoscopic activity, 100% had normalization of an elevated CRP, and 83.3% experienced a decrease in FCP by >50%. There were no new safety signals. Conclusion: Over two-thirds of patients met the primary endpoint of persistence on therapy without requiring surgery, steroids, or additional biologic/small molecule inhibitor during follow-up. In a subset of patients who had adequate baseline and follow up objective data, the majority of patients had improvement in mucosal healing, decrease by 50% in FCP, and normalization of CRP. This study shows promising results that prolonged upadacitinib induction or dose re-escalation may improve clinical outcomes in a medically refractory patient population.