Comparison of risankizumab and upadacitinib treatment persistence according to disease location in patients with Crohn’s disease: data from the CREdIT registry

IMPORTANCE: Comparative data on risankizumab and upadacitinib in Crohn's disease are limited. OBJECTIVE: We aimed to compare the real-world effectiveness of the 2 therapies, measured by treatment persistence, and to assess whether it differed according to disease location. DESIGN: Retrospective cohort study. SETTING: Nationwide CREdIT prospective registry. PARTICIPANTS: Pediatric and adult patients with Crohn's disease. EXPOSURES: Initiation of risankizumab or upadacitinib. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment persistence, defined as time from therapy initiation to drug discontinuation, with censoring at the last follow-up, and evaluated using weighted Cox models clustered by patient. Missing covariates were handled using multiple imputation, and treatment groups were balanced using inverse probability weighting (IPW) based on propensity scores. RESULTS: A total of 560 treatment observations were included (264 risankizumab and 296 upadacitinib), most representing advanced lines of therapy. Following IPW, upadacitinib was associated with a higher risk of treatment discontinuation than risankizumab (Hazard ratio [HR] 1.86, 95% CI, 1.02-3.39). Among patients with ileal involvement (L1/L3), upadacitinib was associated with a higher discontinuation risk (HR 2.56, 95% CI, 1.49-4.40), whereas no difference was observed in patients with isolated colonic disease (L2; HR 0.66, 95% CI, 0.19-2.33). The interaction between upadacitinib therapy and isolated colonic involvement was significant (P = .049). CONCLUSIONS AND RELEVANCE: In this nationwide real-world cohort of predominantly advanced treatment-experienced patients with Crohn's disease, risankizumab was associated with greater treatment persistence than upadacitinib. The superiority of risankizumab was observed mainly in patients with ileal involvement, and these findings suggest that disease location may be an important consideration when choosing between the 2 therapies.