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COMPARATIVE EFFECTIVENESS OF TOFACITINIB VERSUS UPADACITINIB FOR THE TREATMENT OF ACUTE SEVERE ULCERATIVE COLITIS: RESULTS OF AN INTERNATIONAL MULTICENTER STUDY

Sailish Honap 1, Joelle St-Pierre 2, Michael Colwill 3, Kamal Vijaykant Patel 3, Catherine Le Berre 4, Bénédicte Caron 5, Akira Nogami 6, Taku Kobayashi 7, Romain Altwegg 8, David Laharie 9, Xavier Hebuterne 10, Maria Nachury 11, Xavier Roblin 12, Matthieu Uzzan 13, Paulo Gustavo Kotze 14, Milan Lukas 15, Sophie Vieujean 16, Ferdinando D'Amico 17, Ahmad Albshesh 18, Lucas Guillo 19, Mathurin Fumery 20, Stephane NANCEY 21, Byong Duk Ye 22, Daniel Bergemalm 23, Jonas Halfvarson 23, Anthony Buisson 24, Konstantinos Karmiris 25, David T. Rubin 26, Eric Vicaut 27, Laurent Peyrin-Biroulet 28

Affiliations

1 St George's University Hospitals NHS Foundation Trust, London, United Kingdom|||King's College London, London, United Kingdom

2 University of Calgary, Calgary, Canada

3 St George's University Hospitals NHS Foundation Trust, London, United Kingdom

4 Université de Nantes, Nantes, France

5 CHRU Nancy, INSERM NGERE, Université de Lorraine, Nancy, France

6 Toho University Omori Medical Center, Tokyo, Japan

7 Kitasato University Kitasato Institute Hospital, Suginami-ku, Japan

8 CHU St Eloi Montpellier, Montpellier, France

9 CHU de Bordeaux Hopital Haut-Leveque Dept. de Gastroenterologie, Pessac Cedex, France

10 CHU of Nice and University Côte d'Azur, Nice, France

11 Universite de Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France

12 University Hospital of Saint-Etienne, Saint Etienne, France

13 Hopital Henri Mondor, Paris, France

14 Catholic University Of Paraná - Curitiba - Pr - Brazil, Pinhais, Brazil

15 ISCARE Clinical Centre, Prague, Czechia

16 CHU Liege Hospital, Liège, Belgium

17 IRCCS San Raffaele Hospital, Milan, Italy

18 Sheba Medical Center, Jaljulia, Israel

19 University Hospital of Marseille Nord and University of Aix-Marseille, Marseille, France

20 Amiens University Hospital, Amiens, France

21 Lyon Sud Hospital, Lyon, France

22 Asan Medical Center, Seoul, Korea, Republic of

23 Örebro University, Örebro, Sweden

24 CHU Estaing Clermont-Ferrand, Clermont-Ferrand, France

25 Venizeleio General Hospital, Heraklion, Greece

26 University of Chicago Medicine, Chicago, United States

27 Hôpital Lariboisière, Assistance Publique–Hopitaux de Paris, Paris, France

28 CHRU Nancy, INSERM NGERE, Université de Lorraine, Vandoeuvre-les-Nancy, France

Summary

AI Generated

This multicenter retrospective study of 111 hospitalized patients with acute severe ulcerative colitis found that tofacitinib and upadacitinib had similar effectiveness for inducing remission and preventing colectomy with comparable safety profiles.

Upadacitinib showed higher early response rates at days 3-7 (84% vs 54%, p=0.02), but clinical response and remission rates were comparable between the two JAK inhibitors at day 98 and day 182.
Colectomy-free survival probabilities at days 98 and 182 were similar for tofacitinib (79%/75%) and upadacitinib (80%/78%) with no significant difference (p=0.99).
In sub-analysis of salvage therapy use (tofacitinib n=35, upadacitinib n=31), effectiveness outcomes were similar across both groups.
Adverse event frequencies were comparable between the two treatments across the 111 patients enrolled from 23 international centers.
This is the first comparative study and largest case series of JAK inhibitors in acute severe ulcerative colitis, though the authors note that prospective studies with longer follow-up are needed to validate findings.

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Abstract

Introduction

Tofacitinib and upadacitinib are Janus kinase (JAK) inhibitors that are increasingly used for the treatment of acute severe ulcerative colitis (ASUC). However, comparative analyses of safety and effectiveness have not been performed for their use in this setting.

Aims & Methods

This multicenter, retrospective study enrolled hospitalized adult patients treated with tofacitinib or upadacitinib for ASUC between January 2019 and June 2024. The main outcomes were clinical response, clinical remission, and colectomy-free survival. Propensity-adjusted analyses using inverse probability treatment weighting (IPTW), and double robust estimations (DRE) were used to control for confounding factors.

Results

In total, 111 patients (60 tofacitinib, 51 upadacitinib) were enrolled across 23 international centers. JAK inhibitors were used to induce response in 86 (77%) patients and used to maintain response after adequate intravenous steroid response in 25 (23%). The median follow up was 31 weeks (IQR 13-64). Between days 3-7 after treatment initiation, upadacitinib was associated with greater response rates 84% vs. 54%, p=0.02, but response/remission were comparable at day 98 (45%/36% vs 55/48%) and day 182 (29/29% vs. 39/34%). Sub-analyses for JAK inhibitor use as salvage therapy (tofacitinib (n=35) vs. upadacitinib (n=31)) showed similar effectiveness outcomes across both groups. The probabilities of colectomy-free survival at days 98/182 for tofacitinib and upadacitinib were 79%/75% and 80%/78%, respectively, with no significant differences in the comparison of survival curves, p=0.99. Treatment failure rates (where JAK inhibitor was used to maintain remission) were similar at days 98 and 182. The frequency of adverse events was comparable.

Conclusion

This is the first comparative study of JAK inhibitors in ASUC and presents the largest series of JAK inhibitor-treated patients to date. Tofacitinib and upadacitinib appear to have similar effectiveness for inducing remission and preventing colectomy with comparable safety outcomes. Further prospective studies with longer-term follow up are needed to validate these findings.

Disclosure

No conflicts of interest for this study. No funding received.

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

Treatment outcomes in IBD (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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SPATIALLY DIFFERENTIATED MEASUREMENT OF INFLAMMATORY CELLS WITH DEEP LEARNING REVEALS THE HETEROGENEITY OF CHANGES IN ULCERATIVE COLITIS

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