Brigida Barberio, Ferdinando D'Amico, Lucrezia Laterza, Cristina Bezzio, Gabriele Dragoni, Anna Viola, Alessia Todeschini, Mariabeatrice Principi, Sara Onali, Chiara Viganò, Maria Cappello, Giammarco Mocci, Angelo Viscido, Giorgia Bodini, Davide Giuseppe Ribaldone, Irene Marafini, Daniela Pugliese, Alessandro Massari, Simone Saibeni, Luca Pastorelli, Laura Melotti, Irene Maria Bambina Bergna, Antonietta Gerarda Gravina, Federico Desideri, Manuela Merli, Lorenzo Bertani, Rocco Spagnuolo, Nicola Imperatore, Concetta Ferracane, Alessandro Quadarella, Imma Di Luna, Vincenza Tortorella, Silvia Mazzuoli, Carla Felice, Paola Balestrieri, Daniele Balducci, Annalisa Aratari, Andrea Buda, Silvio Danese, Franco Scaldaferri, Alessandro Armuzzi, Fabiana Zingone, Javier Chahuan, Edoardo V Savarino
Upadacitinib was effective and well-tolerated in AT-experienced CD, including patients with active EIMs, with induction benefit maintained through 6 months without novel safety signals.
BACKGROUND AND AIMS: Upadacitinib is an oral selective JAK1 inhibitor approved for moderate-to-severe Crohn's disease (CD), but real-world prospective multicentre data in advanced therapy-experienced (AT-experienced) patients are limited. The UPGRADE-CD study evaluated its effectiveness and safety.
METHODS: In this prospective, multicentre, observational study across 38 Italian centres, we enrolled consecutive AT-experienced CD patients initiating upadacitinib. Effectiveness was assessed at weeks 12 and 24, including clinical response (HBI reduction ≥ 3) and remission (HBI ≤ 4), steroid-free counterparts, biomarker normalisation, resolution of extraintestinal manifestations (EIMs) and endoscopic outcomes. Safety was assessed in all patients receiving ≥ 1 dose.
RESULTS: A total of 391 patients were included in the safety analysis and 323 in the efficacy analysis; 48% had failed more than two advanced therapies. Clinical remission reached 51.2% at Week 12 and 54.7% at Week 24 (p = 0.07). Steroid-free clinical response rose from 53.8% to 63.5% (p = 0.09). Active EIMs, present in 39.9% at baseline, resolved completely in 65.7% by Week 24. Higher baseline HBI was the strongest predictor of failure to achieve remission. Discontinuation by Week 24 was 11.3%, mainly from treatment failure (7.2%) and adverse events (3.1%). No major cardiovascular, thromboembolic events or malignancies occurred.
CONCLUSIONS: Upadacitinib was effective and well-tolerated in AT-experienced CD, including patients with active EIMs, with induction benefit maintained through 6 months without novel safety signals.