Comparative Effectiveness and Safety of Tofacitinib, Filgotinib, and Upadacitinib in Ulcerative Colitis: A Multicenter Real-World Cohort Study

INTRODUCTION: Tofacitinib, filgotinib, and upadacitinib are Janus kinase inhibitors (JAKis) available for ulcerative colitis (UC) refractory or intolerant to at least one advanced therapy; their comparative effectiveness in clinical practice remains uncertain. METHODS: We conducted a multicenter retrospective study including adult UC patients initiating tofacitinib, filgotinib, or upadacitinib (September 2020-June 2025). Clinical remission (partial Mayo score ≤ 1), steroid-free clinical remission, biochemical remission, and endoscopic remission (Mayo endoscopic score = 0) were assessed at predefined time-points. Baseline differences were controlled using inverse probability of treatment weighting (IPTW), and time-to-event and longitudinal analyses were performed. RESULTS: After IPTW, the pseudo-population included 627 patients (tofacitinib = 179, filgotinib = 138, upadacitinib = 310). In the weighted cohort, clinical remission probabilities at weeks 8, 24, and 52 were 17.5%, 40.7%, and 61.3% with upadacitinib, 11.8%, 33.8%, and 54.6% with tofacitinib, and 6.7%, 29.0%, and 52.0% with filgotinib, respectively; p < 0.001 at weeks 8 and 24; p = 0.040 at week 52. Steroid-free clinical remission showed a similar gradient (14.2%, 39.2%, and 59.8% with upadacitinib; 9.2%, 31.2%, and 50.8% with tofacitinib; 4.4%, 27.6%, and 49.8% with filgotinib, respectively; all p < 0.001. Biochemical remission was also achieved more frequently with upadacitinib at weeks 8 and 16, although differences between treatments were no longer significant during maintenance. At week 52, endoscopic remission was 18.8% with tofacitinib, 36.6% with upadacitinib, and 19.5% with filgotinib (p = 0.039). Overall adverse events, particularly infections and herpes zoster, were more frequent with tofacitinib, whereas filgotinib had fewer non-serious events; serious adverse events and colectomy risk were uncommon and similar across groups. CONCLUSIONS: All three JAKis were effective, but upadacitinib yielded the highest remission rates, while tofacitinib and filgotinib differed mainly in safety, supporting individualized drug positioning according to efficacy needs and patient-specific risks.

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Journal
Advances in Therapy
Published
2026-05-09
DOI
https://doi.org/10.1007/s12325-026-03622-3
Primary Topic
Inflammatory Bowel Disease
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article
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article

Comparative Effectiveness and Safety of Tofacitinib, Filgotinib, and Upadacitinib in Ulcerative Colitis: A Multicenter Real-World Cohort Study

Rita Monterubbianesi, Fabio Cortellini, P. Capone, Domenico Catarella et al.
Advances in Therapy
Inflammatory Bowel Disease
article

Comparative Effectiveness and Safety of Tofacitinib, Filgotinib, and Upadacitinib in Ulcerative Colitis: A Multicenter Real-World Cohort Study

Rita Monterubbianesi, Fabio Cortellini, P. Capone, Domenico Catarella, Raffaele Pellegrino, Maria Giovanna Graziani, Antonietta Gerarda Gravina, Gian Marco Giorgetti, Alessia Immacolata Cazzato, L. Donnarumma, Patrizio Scarozza, V. D’Onofrio, Antonio Tursi, Marta Patturelli, Michela Di Fonzo, Francesco Bachetti, Guido Daniele Villani, Dario D’Agostino, Costantino Zampaletta, A. Scarcelli, Paolo Tonti, Federica Gaiani, Stefano Rodinò, Caterina Mucherino, Giulia Zerboni, E D'Antonio, Ladislava Sebkova, Giuseppina Grasso, Ileana Luppino, Laura Montesano, Davide Checchin, Giovanni Cataletti, Giuseppe Pranzo, Marcello Picchio, Giulia Rocco, Viviana Neve, Stefano Kayali, Giammarco Mocci, Giorgia Bodini, Roberto Lorenzetti, Valeria Clemente, Silvia Sedda, Walter Elisei, Carlotta Sacchi, Francesca Maria Onidi, C. Cassieri, Giacomo Forti, Simona Piergallini, Lorenzo Bertani, Maddalena Zippi, Davide Giuseppe Ribaldone, Federico Iacopini, Berardino D’Ascoli, Manuela Marzo, Giuliana Vespere, Maria Carla Di Paolo, Andrea Cocco, Antonio Cuomo, Raffaele Colucci, Stefano Scorza, Serafina Fiorella, Laurino Grossi, Linda Ceccarelli, Domenico Morano, Elisabetta Antonelli, Mariaelena Serio, C De Barba, Antonio Ferronato, Italian Network for Inflammatory Bowel Diseases (IN‐IBD), Cristiano Pagnini, Libera Fanigliulo, Carla Felice, Francesco Luzza, Leonardo Allegretta, Edoardo V. Savarino, Greta Lorenzon, Daniele Napolitano, Girolamo Bevevino, Giovanni Lombardi, Fabiana Zingone, Elisabetta Di Bartolo, Andrea Pasta, Roberta Pica, Alfredo Papa, Francesco Costa, Giovanni Maconi, Paolo Usai Satta, Rocco Spagnuolo, Franco Scaldaferri, Gabrio Bassotti, Brigida Barberio, Nicola Della Valle
article en

Abstract

INTRODUCTION: Tofacitinib, filgotinib, and upadacitinib are Janus kinase inhibitors (JAKis) available for ulcerative colitis (UC) refractory or intolerant to at least one advanced therapy; their comparative effectiveness in clinical practice remains uncertain. METHODS: We conducted a multicenter retrospective study including adult UC patients initiating tofacitinib, filgotinib, or upadacitinib (September 2020-June 2025). Clinical remission (partial Mayo score ≤ 1), steroid-free clinical remission, biochemical remission, and endoscopic remission (Mayo endoscopic score = 0) were assessed at predefined time-points. Baseline differences were controlled using inverse probability of treatment weighting (IPTW), and time-to-event and longitudinal analyses were performed. RESULTS: After IPTW, the pseudo-population included 627 patients (tofacitinib = 179, filgotinib = 138, upadacitinib = 310). In the weighted cohort, clinical remission probabilities at weeks 8, 24, and 52 were 17.5%, 40.7%, and 61.3% with upadacitinib, 11.8%, 33.8%, and 54.6% with tofacitinib, and 6.7%, 29.0%, and 52.0% with filgotinib, respectively; p < 0.001 at weeks 8 and 24; p = 0.040 at week 52. Steroid-free clinical remission showed a similar gradient (14.2%, 39.2%, and 59.8% with upadacitinib; 9.2%, 31.2%, and 50.8% with tofacitinib; 4.4%, 27.6%, and 49.8% with filgotinib, respectively; all p < 0.001. Biochemical remission was also achieved more frequently with upadacitinib at weeks 8 and 16, although differences between treatments were no longer significant during maintenance. At week 52, endoscopic remission was 18.8% with tofacitinib, 36.6% with upadacitinib, and 19.5% with filgotinib (p = 0.039). Overall adverse events, particularly infections and herpes zoster, were more frequent with tofacitinib, whereas filgotinib had fewer non-serious events; serious adverse events and colectomy risk were uncommon and similar across groups. CONCLUSIONS: All three JAKis were effective, but upadacitinib yielded the highest remission rates, while tofacitinib and filgotinib differed mainly in safety, supporting individualized drug positioning according to efficacy needs and patient-specific risks.

Advances in Therapy
Università Cattolica del Sacro Cuore (IT), University of Parma (IT), University of Padua (IT), Azienda Ospedaliera San Giovanni Addolorata (IT), Policlinico Umberto I (IT), Martin University (US), Agostino Gemelli University Polyclinic (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Ospedale Antonio Cardarelli (IT), Luigi Sacco Hospital (IT), Azienda Ospedaliera San Camillo-Forlanini (IT), AULSS 2 Marca Trevigiana (IT), San Salvatore Hospital (IT), Ospedale di Spoleto (IT), Ospedale A. Perrino (IT), Ospedale Sant'Anna (IT), Ospedale di Santo Spirito (IT), Department of Medical Sciences (RU), CTO Andrea Alesini (IT), Ospedale Veris Delli Ponti Scorrano (IT), Ospedale Madonna Delle Grazie (IT), University of Campania "Luigi Vanvitelli" (IT), Ospedale Infermi di Rimini (IT), Ospedale Annunziata di Cosenza (IT), Nini Hospital (LB), Ospedale L. Bonomo (IT), Ospedale Santa Maria Goretti (IT), St Martin's Hospital (GB), St. Eugenio Hospital (IT), Ospedale Policlinico San Martino (IT), Azienda Ospedale - Università Padova (IT), Azienda Ospedaliera Pugliese Ciaccio (IT), Ospedale Sant'Anna (IT), Ospedale D. Cotugno (IT), Ospedale SS. Annunziata (IT), Carlo Forlanini Hospital (IT), Ospedale Eugenio Morelli (IT), Azienda Usl Toscana Centro (IT), Azienda Sanitaria Locale Roma 3 (IT), Ospedali Riuniti Umberto I (IT), Azienda Ospedaliera G. Brotzu (IT), Catholic University of America (US)
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Inflammatory Bowel Disease
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