JAMA. 2024 Jul 22:e2412414. doi: 10.1001/jama.2024.12414. Online ahead of print.

Edouard Louis ¹, Stefan Schreiber ², Remo Panaccione ³, Peter Bossuyt ⁴, Luc Biedermann ⁵, Jean-Frederic Colombel ⁶, Gareth Parkes ⁷, Laurent Peyrin-Biroulet ⁸, Geert D'Haens ⁹, Tadakazu Hisamatsu ¹⁰, Britta Siegmund ¹¹, Kaichun Wu ¹², Brigid S Boland ¹³, Gil Y Melmed ¹⁴, Alessandro Armuzzi ^15 16, Phillip Levine ¹⁷, Jasmina Kalabic ¹⁸, Su Chen ¹⁷, Ling Cheng ¹⁷, Lei Shu ¹⁷, W Rachel Duan ¹⁷, Valerie Pivorunas ¹⁷, Yuri Sanchez Gonzalez ¹⁷, Ronilda D'Cunha ¹⁷, Ezequiel Neimark ¹⁷, Kori Wallace ¹⁷, Raja Atreya ¹⁹, Marc Ferrante ²⁰, Edward V Loftus Jr ²¹; INSPIRE and COMMAND Study Group

Collaborators, Affiliations collapse

Collaborators

INSPIRE and COMMAND Study Group: 

Domingo Balderramo, Silvina Goncalves, Juan Lasa, Abel Novillo, Orlando Ruffinengo, Sonja Heeren, Walter Reinisch, Filip Baert, Peter Bossuyt, Arnaud Colard, Olivier Dewit, Marc Ferrante, Denis Franchimont, Edouard Louis, Jean-Francois Rahier, Carlos Francesconi, Roberto Kaiser Junior, Rogerio Parra, Ligia Sassaki, Plamen Penchev, Desislav Stanchev, Kenneth Atkinson, Melanie Beaton, Talat Bessissow, Susan Greenbloom, Jean-Rene Lachance, Allen Lim, Remo Panaccione, Jean-Michel Samson, Scott Shulman, Jesse Siffledeen, Ignacio Alfaro, Carlos Valenzuela, Gustavo Walsen, Ping An, Qian Cao, Yan Chen, Youxiang Chen, Xiang Gao, Xiaohua Hou, Naizhong Hu, Yan Li, Fei Liu, Mei Liu, Lu Lungen, Zhihua Ran, Tongyu Tang, Xin Wang, Shaoqi Yang, Qiang Zhan, Guoxin Zhang, Hu Zhang, Jie Zhang, Xiaolan Zhang, Jie Zhong, Xiaoping Zou, Eligio Alvarez, Juan Ricaurte, Vladimir Borzan, Zeljko Krznaric, Zeljko Puljiz, Martin Bortlik, Pavel Svoboda, Jan Ulbrych, Tomas Vanasek, Jens Kjeldsen, Lars Munck, Anja Poulsen, Ezzat Ali, Osama Salem, Hisham Sawah, Imam Waked, Romain Altwegg, Mathurin Flamant, Mathurin Fumery, Xavier Hebuterne, David Laharie, Laurent Peyrin-Biroulet, Xavier Roblin, Xavier Treton, Raja Atreya, Herbert Deppe, Peter Hasselblatt, Arne Kandulski, Jochen Klaus, Thomas Krause, Torsten Kucharzik, Jessica Mertens, Michael Mross, Axel Naumann, Wolfgang Reindl, Ingolf Schiefke, Stefan Schreiber, Stefan Schubert, Britta Siegmund, Andreas Sturm, Georgios Bamias, Ioannis Koutroubakis, Spilios Manolakopoulos, Gerassimos Mantzaris, Maria Tzouvala, Irit Avni-Biron, Eran Goldin, Lior Katz, Adi Lahat-Zok, Arik Segal, Sandro Ardizzone, Alessandro Armuzzi, Michele Cicala, Antonio Colecchia, Rocco Cosintino, Antonio Gasbarrini, Andrea Geccherle, Edoardo Giovanni Giannini, Paolo Gionchetti, Francesco Luzza, Giovanni Monteleone, Antonino Privitera, Simone Saibeni, Marcello Vangeli, Yasuhiko Abe, Nobuo Aoyama, Kunio Asonuma, Yutaka Endo, Motohiro Esaki, Toshimitsu Fujii, Katsuyuki Fukuda, Fumihito Hirai, Yasuhiro Hisanaga, Noriyuki Horiki, Mikitaka Iguchi, Keisuke Ishigami, Yoh Ishiguro, Hiroaki Ito, Yoichi Kakuta, Koji Kamikozuru, Jun Kato, Teruki Kawanishi, Taku Kobayashi, Hiroyuki Kuge, Atsuo Maemoto, Tomoyuki Masuda, Katsuyoshi Matsuoka, Kayoko Matsushima, Masashi Matsushima, Satoshi Motoya, Katsuhiko Nakai, Koichi Nakajima, Masanao Nakamura, Atsushi Nishida, Takahiro Nishikawa, Nobuaki Nishimata, Toshiaki Ochiai, Naoki Ohmiya, Yoshifumi Ohnishi, Shiro Oka, Keiji Ozeki, Daisuke Saito, Masayuki Saruta, Makoto Sasaki, Masahito Shimizu, Ken Sugimoto, Tomohisa Sujino, Takayoshi Suzuki, Hajime Takatori, Noritaka Takatsu, Hidetoshi Takedatsu, Ken Takeuchi, Hiroki Tanaka, Satoki Tokito, Tatsuya Toyokawa, Yoshito Uenoyama, Takatsugu Yamamoto, Takayuki Yamamoto, Hiroshi Yasuda, Kaoru Yokoyama, Aleksejs Derovs, Aldis Pukitis, Laimas Jonaitis, Edita Kazenaite, Lourdes Lol-Be Pinzon Te, Geert D'Haens, Maurice Lutgens, James Brooker, Richard Gearry, Ben Griffiths, Stephen Inns, Michael Schultz, Jerzy Eszyk, Jaroslaw Kierkus, Dariusz Kleczkowski, Adam Kopon, Robert Petryka, Jaroslaw Regula, Tomasz Romanczyk, Grazyna Rydzewska-Wyszkowska, Piotr Sikorski, Michal Talarek, Rute Cerqueira, Tiago Goncalves, Susana Lopes, Paula Ministro, Francisco Portela, Helena Tavares, Mihai-Mircea Diculescu, Adrian Goldis, Andrada Seicean, Alina Agafina, Anton Edin, Evgenia Gerasimova, Maryana Gettueva, Vladimir Kashnikov, Vladimir Rafalskiy, Ksenia Sharapova, Elena Smolyarchuk, Daria Varganova, Sasa Grgov, Igor Jovanovic, Petar Svorcan, Dino Tarabar, Khoon Lin Ling, Jozef Balaz, Juraj Durina, Milos Gregus, Martin Laclav, David Drobne, Eduan Deetlefs, Jonny Peter, Muhammad Rajabally, Jennifer Rosa, Jan van Zyl, John Wright, Jae Hee Cheon, Byung Ik Jang, Sang-Bum Kang, Dukhwan Kim, Tae Oh Kim, Young-Ho Kim, Jonghun Lee, Kang-Moon Lee, Dong Il Park, Geun Am Song, Luisa Castro Laria, Ana Echarri Piudo, Santiago Garcia Lopez, Vincent Hernandez Ramirez, Maria Dolores Martin Arranz, Pilar Varela Trastoy, Maria Vera Mendoza, Mikael Lordal, Luc Biedermann, Benjamin Misselwitz, Chung-Hsin Chang, Jen-Wei Chou, Chia-Jung Kuo, Ching-Pin Lin, Chia-Hung Tu, Huseyin Alkim, Yusuf Erzin, Irfan Soykan, Tetiana Kravchenko, Nataliia Tsarynna, Vira Vyshyvanyuk, Tariq Ahmad, Fraser Cummings, Kapil Kapur, Arthur Kaser, Alexandra Kent, Gareth Parkes, Kamal Patel, Richard Speight, Alan Steel, Faten Aberra, Humberto Aguilar, Badr Al Bawardy, Ashwin Ananthakrishnan, Matthew Barnes, Kendall Beck, Charles Berkelhammer, Brigid Boland, Jeff Bullock, Adeeti Chiplunker, Robin Dalal, Sushila Dalal, Belkis Delgado, Michael DiGiovanna, George Aaron DuVall, Curtis Freedland, Keith Friedenberg, Philip Ginsburg, Tarek Hassanein, Peter Higgins, John Hong, Jason Hou, Vivek Huilgol, Nikhil Inamdar, Saurabh Kapur, David Kerman, Henry Levine, Nilesh Lodhia, Edward Loftus, Jaime Mayoral, Donald McNeil, Gil Melmed, Andria Mushahwar, Harry Ojeas, Bhaktasharan Patel, Raymond Phillips, Joe Pouzar, Harry Sarles Jr, Joel Schock, Shahriar Sedghi, Nirav Shah, Junaid Siddiqui, David Stokesberry, Le-Chu Su, Arun Swaminath, Dharmendra Verma, John Weber, Ziad Younes, Timothy Zisman

Author information

¹Department of Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium.

²Department of Internal Medicine, University Hospital Schleswig-Holstein, Christian-Albrecht University of Kiel, Kiel, Germany.

³Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.

⁴Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium.

⁵Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

⁶Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.

⁷Department of Gastroenterology, Royal London Hospital, Barts Health NHS Trust, London, England.

⁸Department of Gastroenterology and INSERM U1256, University Hospital of Nancy, Lorraine University, Vandoeuvre, France.

⁹Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.

¹⁰Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan.

¹¹Department of Gastroenterology, Infectiology and Rheumatology, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

¹²State 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.

¹³Division of Gastroenterology, University of California-San Diego, La Jolla.

¹⁴F. Widjaja Inflammatory Bowel Disease Institute, Cedars Sinai Medical Center, Los Angeles, California.

¹⁵IBD Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

¹⁶Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

¹⁷AbbVie Inc, North Chicago, Illinois.

¹⁸AbbVie Deutschland GmbH and Co KG, Ludwigshafen, Germany.

¹⁹First Department of Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

²⁰Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

²¹Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.

PMID: 39037800

PMCID: PMC11264075 (available on 2025-01-22)

DOI: 10.1001/jama.2024.12414

Abstract

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 adverse event signals 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.