ClinGastroenterolHepatol. 2024Sep24:S15423565(24)008607.doi:10.1016/j.cgh.2024.08.032. Online ahead of print.

Jean-Frédéric Colombel ¹, Ana P Lacerda ², Peter M Irving ³, Remo Panaccione ⁴, Walter Reinisch ⁵, Florian Rieder ⁶, Adam Steinlauf ⁷, David Schwartz ⁸, Tian Feng ², Elena Dubcenco ², Samuel I Anyanwu ², F Stephen Laroux ⁹, Colla Cunneen ², Nick Powell ¹⁰

Author information

¹Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: jean-frederic.colombel@mssm.edu.

²AbbVie Inc., North Chicago, Illinois.

³IBD Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

⁴Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.

⁵Department of Internal Medicine, Medical University of Vienna, Vienna, Austria.

⁶Department of Gastroenterology, Hepatology, & Nutrition, Digestive Diseases Institute, Cleveland Clinic, Cleveland, Ohio.

⁷Department of Gastroenterology, Mount Sinai Hospital, New York, New York.

⁸Department of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.

⁹AbbVie Bioresearch Center, Worcester, Massachusetts.

¹⁰Division of Digestive Diseases, Imperial College London, London, United Kingdom.

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 (2:1) to once-daily upadacitinib 45 mg (UPA45) or placebo for 12 weeks. UPA45 clinical responders were rerandomized (1:1:1) to upadacitinib 15 mg (UPA15), 30 mg (UPA30), 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 (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; UPA45, 44.7%, n/N = 17/38; P = .003) and maintenance (placebo, 0%, n/N = 0/11; UPA15, 28.6%, n/N = 4/14; P = .105; UPA30, 23.1% n/N = 3/13; P = .223) and closure of perianal fistula external openings (induction: placebo, 4.8%, n/N = 2/42; UPA45, 22.1%, n/N = 19/86; P = .013; maintenance: placebo, 0%, n/N = 0/30; UPA15, 18.8%, n/N = 6/32; P = .024; UPA30, 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: U-EXCEL (NCT03345849), U-EXCEED (NCT03345836), U-ENDURE (NCT03345823).