Risankizumab for Ulcerative Colitis
Author:
Louis Edouard1, Schreiber Stefan2, Panaccione Remo3, Bossuyt Peter4, Biedermann Luc5, Colombel Jean-Frederic6, Parkes Gareth7, Peyrin-Biroulet Laurent8, D’Haens Geert9, Hisamatsu Tadakazu10, Siegmund Britta11, Wu Kaichun12, Boland Brigid S.13, Melmed Gil Y.14, Armuzzi Alessandro1516, Levine Phillip17, Kalabic Jasmina18, Chen Su17, Cheng Ling17, Shu Lei17, Duan W. Rachel17, Pivorunas Valerie17, Sanchez Gonzalez Yuri17, D’Cunha Ronilda17, Neimark Ezequiel17, Wallace Kori17, Atreya Raja19, Ferrante Marc20, Loftus Edward V.21, , Balderramo Domingo22, Goncalves Silvina22, Lasa Juan22, Novillo Abel22, Ruffinengo Orlando22, Heeren Sonja22, Reinisch Walter22, Baert Filip22, Bossuyt Peter22, Colard Arnaud22, Dewit Olivier22, Ferrante Marc22, Franchimont Denis22, Louis Edouard22, Rahier Jean-Francois22, Francesconi Carlos22, Kaiser Junior Roberto22, Parra Rogerio22, Sassaki Ligia22, Penchev Plamen22, Stanchev Desislav22, Atkinson Kenneth22, Beaton Melanie22, Bessissow Talat22, Greenbloom Susan22, Lachance Jean-Rene22, Lim Allen22, Panaccione Remo22, Samson Jean- Michel22, Shulman Scott22, Siffledeen Jesse22, Alfaro Ignacio22, Valenzuela Carlos22, Walsen Gustavo22, An Ping22, Cao Qian22, Chen Yan22, Chen Youxiang22, Gao Xiang22, Hou Xiaohua22, Hu Naizhong22, Li YAN22, Liu Fei22, Liu Mei22, Lungen Lu22, Ran Zhihua22, Tang Tongyu22, Wang Xin22, Yang Shaoqi22, Zhan Qiang22, Zhang Guoxin22, Zhang Hu22, Zhang Jie22, Zhang Xiaolan22, Zhong Jie22, Zou Xiaoping22, Alvarez Eligio22, Ricaurte Juan22, Borzan Vladimir22, Krznaric Zeljko22, Puljiz Zeljko22, Bortlik Martin22, Svoboda Pavel22, Ulbrych Jan22, Vanasek Tomas22, Kjeldsen Jens22, Munck Lars22, Poulsen Anja22, Ali Ezzat22, Salem Osama22, Sawah Hisham22, Waked Imam22, Altwegg Romain22, FLAMANT Mathurin22, Fumery Mathurin22, Hebuterne Xavier22, Laharie David22, Peyrin-Biroulet Laurent22, Roblin Xavier22, Treton Xavier22, Atreya Raja22, Deppe Herbert22, Hasselblatt Peter22, Kandulski Arne22, Klaus Jochen22, Krause Thomas22, Kucharzik Torsten22, Mertens Jessica22, Mross Michael22, Naumann Axel22, Reindl Wolfgang22, Schiefke Ingolf22, Schreiber Stefan22, Schubert Stefan22, Siegmund Britta22, Sturm Andreas22, Bamias Georgios22, Koutroubakis Ioannis22, Manolakopoulos Spilios22, Mantzaris Gerassimos22, Tzouvala Maria22, Avni-Biron Irit22, Goldin Eran22, Katz Lior22, Lahat-Zok Adi22, Segal Arik22, Ardizzone Sandro22, Armuzzi Alessandro22, Cicala Michele22, Colecchia Antonio22, Cosintino Rocco22, Gasbarrini Antonio22, Geccherle Andrea22, Giannini Edoardo Giovanni22, Gionchetti Paolo22, Luzza Francesco22, Monteleone Giovanni22, Privitera Antonino22, Saibeni Simone22, Vangeli Marcello22, Abe Yasuhiko22, Aoyama Nobuo22, Asonuma Kunio22, Endo Yutaka22, Esaki Motohiro22, Fujii Toshimitsu22, Fukuda Katsuyuki22, Hirai Fumihito22, Hisanaga Yasuhiro22, Horiki Noriyuki22, Iguchi Mikitaka22, Ishigami Keisuke22, Ishiguro Yoh22, Ito Hiroaki22, Kakuta Yoichi22, Kamikozuru Koji22, Kato Jun22, Kawanishi Teruki22, Kobayashi Taku22, Kuge Hiroyuki22, Maemoto Atsuo22, Masuda Tomoyuki22, Matsuoka Katsuyoshi22, Matsushima Kayoko22, Matsushima Masashi22, Motoya Satoshi22, Nakai Katsuhiko22, Nakajima Koichi22, Nakamura Masanao22, Nishida Atsushi22, Nishikawa Takahiro22, Nishimata Nobuaki22, Ochiai Toshiaki22, Ohmiya Naoki22, Ohnishi Yoshifumi22, Oka Shiro22, Ozeki Keiji22, Saito Daisuke22, Saruta Masayuki22, Sasaki Makoto22, Shimizu Masahito22, Sugimoto Ken22, Sujino Tomohisa22, Suzuki Takayoshi22, Takatori Hajime22, Takatsu Noritaka22, Takedatsu Hidetoshi22, Takeuchi Ken22, Tanaka Hiroki22, Tokito Satoki22, Toyokawa Tatsuya22, Uenoyama Yoshito22, Yamamoto Takatsugu22, Yamamoto Takayuki22, Yasuda Hiroshi22, Yokoyama Kaoru22, Derovs Aleksejs22, Pukitis Aldis22, Jonaitis Laimas22, Kazenaite Edita22, Pinzon Te Lourdes Lol-be22, D'Haens Geert22, Lutgens Maurice22, Brooker James22, Gearry Richard22, Griffiths Ben22, Inns Stephen22, Schultz Michael22, Eszyk Jerzy22, Kierkus Jaroslaw22, Kleczkowski Dariusz22, Kopon Adam22, Petryka Robert22, Regula Jaroslaw22, Romanczyk Tomasz22, Rydzewska-Wyszkowska Grazyna22, Sikorski Piotr22, Talarek Michal22, Cerqueira Rute22, Goncalves Tiago22, Lopes Susana22, Ministro Paula22, Portela Francisco22, Tavares Helena22, Diculescu Mihai-Mircea22, Goldis Adrian22, Seicean Andrada22, Agafina Alina22, Edin Anton22, Gerasimova Evgenia22, Gettueva Maryana22, Kashnikov Vladimir22, Rafalskiy Vladimir22, Sharapova Ksenia22, Smolyarchuk Elena22, Varganova Daria22, Grgov Sasa22, Jovanovic Igor22, Svorcan Petar22, Tarabar Dino22, Ling Khoon Lin22, Balaz Jozef22, Durina Juraj22, Gregus Milos22, Laclav Martin22, Drobne David22, Deetlefs Eduan22, Peter Jonny22, Rajabally Muhammad22, Rosa Jennifer22, van Zyl Jan22, Wright John22, Cheon Jae Hee22, Jang Byung Ik22, Kang Sang-Bum22, Kim Dukhwan22, Kim Tae Oh22, Kim Young-Ho22, Lee Jonghun22, Lee Kang-Moon22, Park Dong Il22, Song Geun Am22, Castro Laria Luisa22, Echarri Piudo Ana22, Garcia Lopez Santiago22, Hernandez Ramirez Vincent22, Martin Arranz Maria Dolores22, Varela Trastoy Pilar22, Vera Mendoza Maria22, Lordal Mikael22, Biedermann Luc22, Misselwitz Benjamin22, Chang Chung-Hsin22, Chou Jen-Wei22, Kuo Chia-Jung22, Lin Ching-Pin22, Tu Chia-Hung22, Alkim Huseyin22, Erzin Yusuf22, Soykan Irfan22, Kravchenko Tetiana22, Tsarynna Nataliia22, Vyshyvanyuk Vira22, Ahmad Tariq22, Cummings Fraser22, Kapur Kapil22, Kaser Arthur22, Kent Alexandra22, Parkes Gareth22, Patel Kamal22, Speight Richard22, Steel Alan22, Aberra Faten22, Aguilar Humberto22, Al Bawardy Badr22, Ananthakrishnan Ashwin22, Barnes Matthew22, Beck Kendall22, Berkelhammer Charles22, Boland Brigid22, Bullock Jeff22, Chiplunker Adeeti22, Dalal Robin22, Dalal Sushila22, Delgado Belkis22, DiGiovanna Michael22, DuVall George Aaron22, Freedland Curtis22, Friedenberg Keith22, Ginsburg Philip22, Hassanein Tarek22, Higgins Peter22, Hong John22, Hou Jason22, Huilgol Vivek22, Inamdar Nikhil22, Kapur Saurabh22, Kerman David22, Levine Henry22, Lodhia Nilesh22, Loftus Edward22, Mayoral Jaime22, McNeil Donald22, Melmed Gil22, Mushahwar Andria22, Ojeas Harry22, Patel Bhaktasharan22, Phillips Raymond22, Pouzar Joe22, Sarles Jr. Harry22, Schock Joel22, Sedghi Shahriar22, Shah Nirav22, Siddiqui Junaid22, Stokesberry David22, Su Le-Chu22, Swaminath Arun22, Verma Dharmendra22, Weber John22, Younes Ziad22, Zisman Timothy22
Affiliation:
1. Department of Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium 2. Department of Internal Medicine, University Hospital Schleswig-Holstein, Christian-Albrecht University of Kiel, Kiel, Germany 3. Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada 4. Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium 5. Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland 6. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 7. Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, England 8. Department of Gastroenterology and INSERM U1256, University Hospital of Nancy, Lorraine University, Vandoeuvre, France 9. Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, the Netherlands 10. Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan 11. Department of Gastroenterology, Infectiology and Rheumatology, Charité–Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany 12. 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 13. Division of Gastroenterology, University of California–San Diego, La Jolla 14. F. Widjaja Inflammatory Bowel Disease Institute, Cedars Sinai Medical Center, Los Angeles, California 15. IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy 16. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy 17. AbbVie Inc, North Chicago, Illinois 18. AbbVie Deutschland GmbH and Co KG, Ludwigshafen, Germany 19. First Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany 20. Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium 21. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota 22. for the INSPIRE and COMMAND Study Group
Abstract
ImportanceThe clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown.ObjectiveTo evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis.Design, Setting, and ParticipantsTwo 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.InterventionsFor 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 MeasuresThe 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.ResultsAmong 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 adverse event signals were detected in the treatment groups.Conclusion and RelevanceCompared 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 RegistrationClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135
Publisher
American Medical Association (AMA)
Cited by
2 articles.
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