• Edward V Loftus, Julian Panés, Ana P Lacerda, Laurent Peyrin-Biroulet, Geert D'Haens, Remo Panaccione, Walter Reinisch, Edouard Louis, Minhu Chen, Hiroshi Nakase, Jakob Begun, Brigid S Boland, Charles Phillips, Mohamed-Eslam F Mohamed, Jianzhong Liu, Ziqian Geng, Tian Feng, Elena Dubcenco, and Jean-Frederic Colombel.
• From the Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN (E.V.L.); the Inflammatory Bowel Diseases Unit, Hospital Clinic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona (J.P.); AbbVie, North Chicago, IL (A.P.L., C.P., M-E.F.M., J.L., Z.G., T.F., E.D.); the Department of Gastroenterology and INSERM Unité 1256, Nutrition-Genetics and Environmental Risk Exposure, Faculty of Medicine, University Hospital of Nancy, Lorraine University, Vandoeuvre, France (L.P.-B.); the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada (R.P.); the Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna (W.R.); the Department of Hepato-Gastroenterology and Digestive Oncology, University Hospital Centre Hospitalier Universitaire of Liège, Liège, Belgium (E.L.); the Division of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (M.C.); the Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan (H.N.); the Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, QLD, Australia (J.B.); the Division of Gastroenterology, University of California, San Diego, La Jolla (B.B.); and the Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York (J.-F.C.).
• N. Engl. J. Med. 2023 May 25; 388 (21): 196619801966-1980.

BackgroundUpadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn's disease.MethodsIn two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn's disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn's Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn's Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]).ResultsA total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib.ConclusionsUpadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn's disease. (Funded by AbbVie; U-EXCEL, U-EXCEED, and U-ENDURE ClinicalTrials.gov numbers, NCT03345849, NCT03345836, and NCT03345823.).Copyright © 2023 Massachusetts Medical Society.

33 keywords...

hide…