[en] IMPORTANCE: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. OBJECTIVE: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. DESIGN, SETTING, AND PARTICIPANTS: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. INTERVENTIONS: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. RESULTS: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. CONCLUSION AND RELEVANCE: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Schreiber, Stefan; Department of Internal Medicine, University Hospital Schleswig-Holstein, Christian-Albrecht University of Kiel, Kiel, Germany.
Panaccione, Remo; Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.
Bossuyt, Peter; Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium.
Biedermann, Luc; Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
Colombel, Jean-Frederic; Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Parkes, Gareth; Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, England.
Peyrin-Biroulet, Laurent; Department of Gastroenterology and INSERM U1256, University Hospital of Nancy, Lorraine University, Vandoeuvre, France.
D'Haens, Geert; Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Hisamatsu, Tadakazu; Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan.
Siegmund, Britta; Department of Gastroenterology, Infectiology and Rheumatology, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Wu, Kaichun; State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
Boland, Brigid S; Division of Gastroenterology, University of California-San Diego, La Jolla.
Melmed, Gil Y; F. Widjaja Inflammatory Bowel Disease Institute, Cedars Sinai Medical Center, Los Angeles, California.
Armuzzi, Alessandro; IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. ; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
Levine, Phillip; AbbVie Inc, North Chicago, Illinois.
Kalabic, Jasmina; AbbVie Deutschland GmbH and Co KG, Ludwigshafen, Germany.
Chen, Su; AbbVie Inc, North Chicago, Illinois.
Cheng, Ling; AbbVie Inc, North Chicago, Illinois.
Shu, Lei; AbbVie Inc, North Chicago, Illinois.
Duan, W Rachel; AbbVie Inc, North Chicago, Illinois.
Pivorunas, Valerie; AbbVie Inc, North Chicago, Illinois.
Sanchez Gonzalez, Yuri; AbbVie Inc, North Chicago, Illinois.
D'Cunha, Ronilda; AbbVie Inc, North Chicago, Illinois.
Neimark, Ezequiel; AbbVie Inc, North Chicago, Illinois.
Wallace, Kori; AbbVie Inc, North Chicago, Illinois.
Atreya, Raja; First Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Ferrante, Marc; Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Loftus, Edward V Jr; Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
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