Multicenter Real-World Outcomes of Risankizumab in Crohn's Disease: The RESOLVE IG-IBD Study

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.