Achievement of Endoscopic Remission After Induction Reduces Hospitalization Burden in Crohn's Disease: Findings From a Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials

Background Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled data from 52-week Phase III maintenance trials of risankizumab and upadacitinib in patients with moderate-to-severe active CD.Methods Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission was defined as a Simple Endoscopic Score for Crohn's Disease (SES-CD) of no greater than 4, with at least a 2-point reduction vs induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm.Results Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with incidence rate ratios of 0.45 (95% confidence interval [CI], 0.22-0.95, p = 0.036) and 0.71 (95% CI, 0.44-1.14, p = 0.156) for long-term disease-related and all-cause hospitalizations, respectively.Conclusions Week 12 endoscopic remission is independently associated with a reduction in 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD. Graphical Abstract