Upadacitinib as a rescue therapy for steroid- and infliximab-refractory acute severe ulcerative colitis: short- and long-term effectiveness and safety in a multicenter cohort study

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ID: 322066
2026
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Abstract
Abstract Background Acute severe active ulcerative colitis (ASUC) often requires rescue therapy when standard medical treatment fails. Data on the use of upadacitinib (UPA) as a rescue option after failure of steroids and infliximab (IFX) and on the long-term outcomes of UPA treatment up to 48 weeks, remain scarce. Methods We evaluated hospitalized patients with ASUC (Truelove and Witts criteria) who received UPA following the failure of intravenous corticosteroids (IV-CS) and IFX. Outcomes included UPA persistence, clinical remission (CR), partial Mayo score (pMAYO) ≤ 2, clinical response (≥3-point reduction in pMAYO), and colectomy rates over 48 weeks of follow-up. Results Fifty patients with ASUC from 11 centers (male, 54%) received UPA treatment following IV-CS/IFX failure. Prior IFX exposure was 86%, and > 50% of the patients had received ≥ 2 biologics. Continuation was 52% overall (week 4, 90%; week 48, 52%). Discontinuation was due to primary nonresponse (42%), secondary loss of response (46%), or other causes (13%). Adverse events related to UPA occurred in 24% of patients and almost all were nonsevere. Stool frequency, rectal bleeding, pMayo score, and C-reactive protein (CRP) improved rapidly by week 1 and were thereafter maintained to week 48. Colectomy occurred in 22% of patients (nearly half of them in week 1). Week 1 CRs were 60%/30% while the week 48 CR rate was 51%. Higher baseline CRP predicted colectomy; no factor affected UPA persistence. Conclusion In this multicenter cohort of patients with ASUC who failed IV-CS and IFX rescue, third-line UPA was associated with a low colectomy rate and sustained response up to 1 year, with an acceptable safety profile. UPA may provide sufficient disease control to prevent or delay colectomy, or to serve as a bridge to alternative therapies. Summary In this retrospective multicenter cohort (11 centers), 50 patients with severe ulcerative colitis refractory to intravenous corticosteroids and infliximab received upadacitinib. Improved symptoms and C-reactive protein (CRP) levels occurred by week 1 and persisted to week 48; colectomy occurred in 22% and adverse events in 24% of patients.
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Authors Nalan Gülşen Ünal, Oğuz Kağan Bakkaloğlu, Taylan Kav, Tuğçe Eşkazan, Haluk Tarık Kani, Atilla Akpınar, P Akincioglu, Gizem Dağcı, İbrahim Şendur, İlker Büyüktorun, Sezgin Barutçu, Güner Kılıç, Göksel Bengı, Bilger Çavuş, N Oruç, Yeşim Özen Alahdab, Özlen Atuğ, Dinc Dinçer, Tarkan Karakan, Ali İbrahim Hatemi, Yusuf Erzın, Ahmet Tezel, Murat Törüner, Filiz Akyüz, Aykut Ferhat Çelik
Journal inflammatory bowel diseases
Year 2026
DOI
10.1093/ibd/izag126
URL
https://doi.org/10.1093/ibd/izag126
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