Re-evaluating Methods for Assessing Differences in Response in Ileal vs Colonic Crohn's Disease: A Post-hoc Analysis of the FITZROY Trial.

Background and aims: The ileum is the most commonly affected segment of the gastrointestinal tract in Crohn's disease [CD]. We aimed to determine whether disease location affects response to filgotinib, a Janus kinase [JAK] inhibitor, in patients with moderately-to-severely active Crohn's disease [CD] and applying appropriate methods to account for differences in measuring disease activity in the ileum compared with the colon.

Methods: This post-hoc analysis of data from the FITZROY phase 2 trial [NCT02048618] compared changes in the Crohn's Disease Activity Index [CDAI] and Simple Endoscopic Score for Crohn's Disease [SES-CD] among patients with ileal-dominant and isolated colonic CD treated with 10 weeks of filgotinib 200 mg daily or placebo. A mixed effects model for repeated measures was used to test whether ileal disease responded differently when compared with colonic disease, by evaluating for effect modification using the interaction term of treatment assignment-by-disease location.

Results: Numerically greater proportions of patients with isolated colonic disease compared to ileal-dominant CD achieved clinical remission [CDAI < 150, 75.9% vs 41.6%] and endoscopic response [SES-CD reduction by 50%, 52.5% vs 15.5%] at Week 10. However, after adjusting for baseline disease activity by disease location and within-patient clustering effects, there was no significant difference in treatment response by disease location [mean difference in ΔCDAI between ileal-dominant vs isolated colonic disease + 9.24 [95% CI: -87.19, +105.67], p = 0.85; mean difference in ΔSES-CD -1.93 [95% CI: -7.03, +3.44], p = 0.48.

Conclusions: Filgotinib demonstrated similar efficacy in ileal-dominant and isolated colonic CD when controlling for baseline disease activity and clustering effects.