Franco Scaldaferri, Federica Di Vincenzo, M Aloi, M. Ascolani, Paola Balestrieri, Lorenzo Bertani, Cristina Bezzio, Giorgia Bodini, Fabrizio Bossa, Emma Calabrese, R Cannatelli, Flavio Caprioli, M. Cappello, Michele Cicala, Ferdinando D’Amico, Silvio Danese, Alice De Bernardi, F.R. De Filippo, F Desideri, Dhanai Di Paolo, A. Di Sario, Massimo Claudio Fantini, Concetta Ferracane, Stefano Festa, Gionata Fiorino, Roberto Gabbiadini, Andrea Geccherle, Viviana Gerardi, Emiliano Giangreco, Antonietta Gerarda Gravina, L. Laterza, Loris Riccardo Lopetuso, Irene Marafini, Mauro Mastronardi, Marco Mendolaro, M. Merli, Giammarco Mocci, S. Onali, Maria Francesca Onidi, Luca Pastorelli, Alessandra Piagnani, Maria Beatrice Principi, Daniela Pugliese, Davide Giuseppe Ribaldone, Antonio Rispo, Fernando Rizzello, Fabrizio Santagata, Edoardo Vincenzo Savarino, Rocco Spagnuolo, A Tursi, Alba Panarese, Silvia Mazzuoli, Angela Variola, Chiara Viganò, Alessandro Armuzzi, on behalf of the RESOLVE Study Group
INTRODUCTION: To assess the effectiveness and safety of Risankizumab (RZB) in a large, nationwide real-world cohort of patients with Crohn's disease (CD). METHODS: We conducted a multicenter, retrospective observational cohort of adults initiating RZB with assessments at weeks 12, 26, and 52. Coprimary end points were (i) week-12 steroid-free clinical remission (SFCR) (Harvey-Bradshaw Index <5 in the absence of systemic corticosteroids or budesonide) and (ii) week-52 endoscopic remission (Simple Endoscopic Score-CD 0-2 or Rutgeerts i0-i1 postoperatively). The main effectiveness analysis was as-observed; a preplanned sensitivity analysis included patients expected to reach week-52 before database lock and applied nonresponder imputation. RESULTS: We included 520 patients, 45.0% failed ≥3 and 54.8% were ustekinumab (UST)-exposed. At week 12, clinical response was 76.5% and 60.8% achieved SFCR. By week 52, SFCR was 65.6%; endoscopic remission occurred in 37.5%, whereas radiologic remission and transmural healing were 24.6% and 9.8%, respectively. UST-naïve patients showed significantly superior early clinical outcomes (week-12 SFCR: 69.8% vs 53.3%) and a higher rate of endoscopic remission at week 52 (56.5% vs 28.6%) compared with UST-exposed patients. Notably, week-52 effectiveness was comparable between patients with 2 and those with ≥3 previous failures. Extraintestinal manifestations decreased over time, whereas perianal disease improved modestly. In the sensitivity cohort (N = 213), SFCR was 47% at week-52. RZB was well-tolerated with no new safety signals identified. DISCUSSION: In a large, refractory, real-world CD population, RZB induced rapid and sustained favorable clinical, endoscopic, and radiologic outcomes. Importantly, one-year effectiveness was similar in patients with 2, and ≥3 previous failures, supporting RZB as a valuable option for a refractory population.