Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn's Disease: A Post Hoc Analysis of 3 Phase 3 Trials.

ABSTRACT

BACKGROUND & AIMS: Efficacy of upadacitinib, an oral Janus kinase inhibitor, for moderate-to-severe Crohn's disease was demonstrated in phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials; this post hoc analysis evaluated upadacitinib outcomes in patients with fistulizing disease in these studies. METHODS: Patients were randomized (21) to once daily upadacitinib 45 mg or placebo for 12 weeks. Upadacitinib 45 mg clinical responders were rerandomized (111) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks. In patients with fistulas (any and perianal), resolution of drainage, closure of external openings, clinical remission, endoscopic response, and safety were assessed. RESULTS: Of 1021 patients in U-EXCEL and U-EXCEED, 143 (14.0%) had any fistulas at baseline (66 draining); of these, most (n = 128) had perianal fistulas (56 draining). Greater proportions of patients receiving upadacitinib vs placebo achieved resolution of drainage of perianal fistulas at the end of induction (placebo 5.6%, n/n = 1/18; upadacitinib 45 mg 44.7%, n/n = 17/38; P = .003) and maintenance (placebo 0%, n/n = 0/11; upadacitinib 15 mg 28.6%, n/n = 4/14; P = .105; upadacitinib 30 mg 23.1% n/n = 3/13; P = .223) and closure of perianal fistula external openings (for induction, placebo 4.8%, n/n = 2/42; upadacitinib 45 mg 22.1%, n/n = 19/86; P = .013; for maintenance, placebo 0%, n/n = 0/30; upadacitinib 15 mg 18.8%, n/n = 6/32; P = .024; upadacitinib 30 mg 16.0%, n/n = 4/25; P = .037). CONCLUSION: Patients with fistulizing disease (primarily perianal) treated with upadacitinib achieved higher rates of resolution of drainage, closure of external openings, clinical remission, and endoscopic response vs placebo. CLINICALTRIALS gov, Numbers NCT03345849 (U-EXCEL), NCT03345836 (U-EXCEED), NCT03345823 (U-ENDURE).