Abstract Italian Network for Inflammatory Bowel Diseases (IN-IBD). Caterina De Barba Gastroenterology Unit Azienda Ospedale-Università di Padova (AOUP) Padua Italy; Raffaele Pellegrino, Department of Precision Medicine, Hepatogastroenterology and Digestive Endoscopy Unit, University of Campania “Luigi Vanvitelli”, Naples; Antonio Ferronato: UOSD di Endoscopia Digestiva ULSS7 Pedemontana Ospedale di Santorso Santorso (VI) Giovanni Cataletti: UOC di Gastroenterologia A.O. “L. Sacco” Milano Giovanni Aragona Patrizia Perazzo: UOC di Gastroenterologia Ospedale “Guglielmo da Saliceto” Piacenza Federica Gaiani Stefano Kayali: UOC di Gastroenterologia ed Endoscopia Digestiva Dipartimento di Medicina e Chirurgia Ospedale Maggiore Università di Parma Parma Fabio Cortellini: UOC di Gastroenterologia ed Endoscopia Digestiva Ospedale” Infermi” Rimini Francesco Costa: UOC di Gastroenterologia Azienda Ospedaliero-Universitaria Pisana Pisa Antonella Scarcelli Mariaelena Serio: UOC di Gastroenterologia Ospedale “San Salvatore” Pesaro Simona Piergallini: UOC di Gastroenterologia IBD Unit Ospedale “A. Murri” Fermo Francesca Maria Onidi Giorgia Orrù Paolo Usai Satta: UOC di Gastroenterologia Azienda Ospedaliera di Rilievo Nazionale “Brotzu” Cagliari Giorgia Orrù: University of Cagliari Department of Medical Sciences and Public Health Cagliari Italy Raffaele Colucci Francesco Bachetti: UOSD di Endoscopia Digestiva Ospedale “San Matteo degli Infermi” Spoleto (PG) Daniele Napolitano: UOC di Medicina Interna e Gastroenterologia Dipartimento di Scienze Mediche e Chirurgiche IRCCS Fondazione “Policlinico Gemelli Università Cattolica del Sacro Cuore Roma Rita Monterubbianesi Michela Di Fonzo: UOC di Gastroenterologia ed Endoscopia Digestiva A.O. “S. Camillo-Forlanini” Roma Cristiano Pagnini: UOC di Gastroenterologia ed Endoscopia Digestiva A.O. “S. Giovanni - Addolorata” Roma Gian Marco Giorgetti Valeria Clemente: UOSD di Endoscopia Digestiva Nutrizionale Ospedale “S. Eugenio” Roma Roberta Pica Andrea Cocco Claudio Cassieri: UOC di Gastroenterologia ed Endoscopia Digestiva Ospedale “S. Pertini” Roma Patrizio Scarozza Girolamo Bevevino Federico Iacopini: UOC di Gastroenterologia ed Endoscopia Digestiva “Ospedale dei Castelli” Ariccia (Roma) Giacomo Forti: UOSD di Endoscopia Digestiva Ospedale “S. Maria Goretti” Latina Laurino Grossi: UOC di Gastroenterologia Ospedale “Spirito Santo” Università “G d’Annunzio” Pescara Serafina Fiorella: UOSD di Gastroenterologia ed Endoscopia Digestiva Ospedale “P. Pio” Vasto (CH) Giovanni Lombardi Marta Patturelli: UOC di Gastroenterologia Azienda Ospedaliera di Rilievo Nazionale “Antonio Cardarelli” Napoli Giuliana Vespere Silvia Sedda : UOC di Gastroenterologia “Ospedale del Mare” ASL NA1 Centro Napoli Caterina Mucherino Elvira D’Antonio: UOC di Gastroenterologia Azienda Ospedaliera “S. Anna e S. Sebastiano” Caserta Pietro Caponei: UOC di Gastroenterologia ed Endoscopia Digestiva Ospedale “T. Maresca” Torre del Greco (NA) Antonio Cuomo UOSD di Gastroenterologia “Umberto I” Nocera Inferiore (SA) Giuseppe Pranzo: UOS di Endoscopia Digestiva Ospedale “Valle D’Itria” Martina Franca (TA) Viviana Neve: UOSD di Gastroenterologia ed Endoscopia Digestiva Ospedale “A. Perrino” Brindisi Libera Fanigliulo: UOC di Gastroenterologia A.O. “S.S. Annunziata” Taranto Leonardo Allegretta UOC di Gastroenterologia ed Endoscopia Digestiva Ospedale “Santa Caterina Novella” Galatina (LE) Manuela Marzo: UOC di Gastroenterologia ed Endoscopia Digestiva Ospedale “Veris-Delli Ponti” Scorrano (LE) Ileana Luppino: UOC di Gastroenterologia ed Endoscopia Digestiva Ospedale “Annunziata” Cosenza Stefano Rodinò Ladislava Sebkova: UOC di Gastroenterologia A.O. “Ciaccio-Pugliese” Catanzaro Francesco Luzza Rocco Spagnuolo: Dipartimento di Scienze Mediche UOC di Fisiopatologia Digestiva Azienda Ospedaliera “Mater Domini” Università di Catanzaro Catanzaro Background To compare the real-world effectiveness and safety of three Janus kinase inhibitors—upadacitinib (UPA), tofacitinib (TOFA), and filgotinib (FILGO)—for ulcerative colitis (UC) across several Italian IBD centers, using propensity weighting to address baseline imbalances. Methods We conducted a multicenter observational cohort including consecutive adults with UC initiating UPA, TOFA, or FILGO. Inverse probability of treatment weighting (IPTW) was applied to balance prespecified covariates. Effectiveness outcomes were clinical remission, steroid-free clinical remission, biochemical remission, and endoscopic remission defined with a Mayo endoscopic subscore=0. Time-to-event analyses used Cox proportional hazards models with interval-censored covariates. Results The pre-IPTW cohort comprised 633 patients (UPA 313; TOFA 181; FILGO 139). After IPTW, effectiveness consistently favored UPA. IPTW-adjusted week-52 remission rates were: clinical remission—UPA 90.5%, TOFA 82.4%, FILGO 76.9% (p = 0.010); steroid-free clinical remission—UPA 88.5%, TOFA 77.0%, FILGO 73.4% (p 0.001); biochemical remission—UPA 73.3%, TOFA 72.7%, FILGO 75.1% (p = 0.200); endoscopic remission—UPA 36.6%, TOFA 18.8%, FILGO 19.5% (p = 0.039). Across interim time points (weeks 12, 24, 36, and 48), UPA maintained higher probabilities of clinical and steroid-free remission. Time-to-event analyses aligned with these patterns. Considering UPA as reference, hazards for achieving clinical remission were lower with TOFA (HR 0.79; 95% CI 0.62–0.99; p = 0.042) and FILGO (HR 0.67; 0.54–0.84; p = 0.001), while for steroid-free remission, HRs were 0.76 (0.59–0.98; p = 0.032) and 0.66 (0.52–0.83; p 0.001), respectively. Biochemical remission hazards did not differ significantly. Surgery-free survival was comparable across agents. Safety profiles diverged for overall AEs, as the incidence per 100 PY was highest with TOFA (135.18), intermediate with UPA (36.07), and lowest with FILGO (15.27; p 0.0001). SAEs were infrequent and similar (2.93, 6.76, and 5.15 per 100 PY for TOFA, UPA, and FILGO; p = 0.374). Colectomy rates were comparable (12.02, 12.90, and 20.69 per 100 PY for TOFA, UPA, and FILGO; p = 0.181). Conclusion In this large Italian multicenter, propensity-weighted real-world study of JAK inhibitors for UC, UPA showed superior effectiveness over TOFA and FILGO for clinical and steroid-free clinical remission through 52 weeks and achieved higher endoscopic remission at week 52, while biochemical remission was similar among agents. Overall, AE incidence was lowest with FILGO and highest with TOFA, whereas SAEs and colectomy rates did not differ meaningfully. These findings support that the treatment selection should integrate efficacy goals with patient-specific safety considerations Conflict of interest: Mocci, Giammarco: No conflict of interest Pasta, Andrea: No conflict of interest Elisei, Walter: No conflict of interest Barberio, Brigida: Brigida Barberio: has served as speaker for Abbvie, Agave, Alfasigma, AGpharma, Johnson & Johnson, Eli Lilly, MSD, Pfizer, Procise, Sofar, Takeda, Unifarco. BB has served as consultant for Abbvie, Eli Lilly, ohnson & Johnson. Savarino, Edoardo Vincenzo: Personal Fees: Takeda, Abbvie, MSD, Janssen, Sofar Maconi, Giovanni: Personal Fees: Abbvie, Arena Pharmaceuticals, Alfa-Wasserman, Fresenius-Kabi, Gilead, Janssen Cilag, Roche Non-financial Support: Takeda, Abbvie, Alfa-Wasserman Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax Ribaldone, Davide Giuseppe: Davide Giuseppe Ribaldone declares the following paid consultancies, lecture fees for the past two years: Johnson & Johnson, Takeda, Celltrion, Alfasigma, Pfizer, Eli Lilly, Abbvie, Sandoz Bodini, Giorgia: No conflict of interest Bertani, Lorenzo: No conflict of interest Ceccarelli, Linda: No conflict of interest Gravina, Antonietta Gerarda: Gravina AG has conducted training activities e.g. educational continuing medical activities (ECM), preceptorship for Pfizer, Galapagos Biopharma, and AbbVie. Picchio, Marcello: No conflict of interest Papa, Alfredo: No conflict of interest Tursi, Antonio: None
Mocci et al. (Thu,) studied this question.