Effectiveness and Safety of Extended Upadacitinib Induction Therapy in Adult Patients with Moderate-to-Severe Active Ulcerative Colitis

Abstract Background Responses to induction therapies for moderate-to-severe active ulcerative colitis (UC) are sufficient, but some patients benefit from prolonged induction to achieve clinical outcomes before transitioning to maintenance dosing. Upadacitinib (UPA), an oral JAK1 inhibitor, is approved in the US. for treatment of moderate-to-severe active UC non-responsive to anti-TNF therapy. However, standard 8-week induction regimen with UPA 45 mg/day may not be sufficient for some patients. We aimed to assess the effectiveness and safety of extended UPA induction for moderate-to-severe active UC. Methods We conducted a retrospective analysis of adults with moderate-to-severe active UC who received UPA 45 mg/day beyond 8 weeks’ induction. Patients with disease-related complications and those lost-to follow-up data after extended induction were excluded. Primary endpoint was clinical response (partial Mayo score (PMS) reduction by ≥ 3). Secondary endpoints included clinical remission (PMS ≤ 2), endoscopic response (Mayo endoscopic score decrease by ≥ 1), improvement in fecal calprotectin (FC) to < 150 ug/dL, and specific adverse events. Results Nine patients were included for analysis. All patients previously failed ≥ 1 biologic therapy, and 5 failed ≥ 2 biologic therapies, of which 1 also failed tofacitinib. Duration of extended UPA induction ranged from 12-24 weeks. Clinical response rate was 78% (7/9) and FC improved to < 150 ug/dL in 71% (5/7). At the time of this report, 3 patients completed 12 weeks UPA induction but have not yet transitioned to maintenance therapy. Of these, 1 achieved clinical response, 1 achieved clinical remission, and 1 has planned colectomy for steroid-refractory UC. Five patients completed UPA extended induction (range 12-24 weeks) and transitioned to UPA 30 mg/day with stable clinical remission and FC < 150 ug/g. Finally, 1 patient discontinued UPA induction after 16 weeks due to non-response and underwent total proctocolectomy. Adverse events included dental abscess (n = 1) and mild COVID-19 infection (n = 2). No patients developed Herpes zoster, VTE, or MACE. Conclusion Our retrospective study suggests extended UPA induction, from 12-24 weeks, is effective in achieving clinical response/remission in patients with moderate-to-severe active UC with a tolerable safety profile. Our clinical response/remission rates are higher than that reported for extended induction in the U-ACCOMPLISH/U-ACHIEVE clinical trials. Larger studies and longer-term follow-up are needed to examine the efficacy and safety of this approach.