Risankizumab for Ulcerative Colitis
Authors: Louis Edouard , Schreiber Stefan , Panaccione Remo , Bossuyt Peter , Biedermann Luc , Colombel Jean-Frederic , Parkes Gareth , Peyrin-Biroulet Laurent , D’Haens Geert , Hisamatsu Tadakazu , Siegmund Britta , Wu Kaichun , Boland Brigid S. , Melmed Gil Y. , Armuzzi Alessandro , Levine Phillip , Kalabic Jasmina , Chen Su , Cheng Ling , Shu Lei , Duan W. Rachel , Pivorunas Valerie , Sanchez Gonzalez Yuri , D’Cunha Ronilda , Neimark Ezequiel , Wallace Kori , Atreya Raja , Ferrante Marc , Loftus Edward V. ,   INSPIRE and COMMAND Study Group, Balderramo Domingo , Goncalves Silvina , Lasa Juan , Novillo Abel , Ruffinengo Orlando , Heeren Sonja , Reinisch Walter , Baert Filip , Bossuyt Peter , Colard Arnaud , Dewit Olivier , Ferrante Marc , Franchimont Denis , Louis Edouard , Rahier Jean-Francois , Francesconi Carlos , Kaiser Junior Roberto , Parra Rogerio , Sassaki Ligia , Penchev Plamen , Stanchev Desislav , Atkinson Kenneth , Beaton Melanie , Bessissow Talat , Greenbloom Susan , Lachance Jean-Rene , Lim Allen , Panaccione Remo , Samson Jean-Michel , Shulman Scott , Siffledeen Jesse , Alfaro Ignacio , Valenzuela Carlos , Walsen Gustavo , An Ping , Cao Qian , Chen Yan , Chen Youxiang , Gao Xiang , Hou Xiaohua , Hu Naizhong , Li Yan , Liu Fei , Liu Mei , Lungen Lu , Ran Zhihua , Tang Tongyu , Wang Xin , Yang Shaoqi , Zhan Qiang , Zhang Guoxin , Zhang Hu , Zhang Jie , Zhang Xiaolan , Zhong Jie , Zou Xiaoping , Alvarez Eligio , Ricaurte Juan , Borzan Vladimir , Krznaric Zeljko , Puljiz Zeljko , Bortlik Martin , Svoboda Pavel , Ulbrych Jan , Vanasek Tomas , Kjeldsen Jens , Munck Lars , Poulsen Anja , Ali Ezzat , Salem Osama , Sawah Hisham , Waked Imam , Altwegg Romain , Flamant Mathurin , Fumery Mathurin , Hebuterne Xavier , Laharie David , Peyrin-Biroulet Laurent , Roblin Xavier , Treton Xavier , Atreya Raja , Deppe Herbert , Hasselblatt Peter , Kandulski Arne , Klaus Jochen , Krause Thomas , Kucharzik Torsten , Mertens Jessica , Mross Michael , Naumann Axel , Reindl Wolfgang , Schiefke Ingolf , Schreiber Stefan , Schubert Stefan , Siegmund Britta , Sturm Andreas , Bamias Georgios , Koutroubakis Ioannis , Manolakopoulos Spilios , Mantzaris Gerassimos , Tzouvala Maria , Viazis Nikolaos , Avni-Biron Irit , Goldin Eran , Katz Lior , Lahat-Zok Adi , Segal Arik , Ardizzone Sandro , Armuzzi Alessandro , Cicala Michele , Colecchia Antonio , Cosintino Rocco , Gasbarrini Antonio , Geccherle Andrea , Giannini Edoardo Giovanni , Gionchetti Paolo , Luzza Francesco , Monteleone Giovanni , Privitera Antonino , Saibeni Simone , Vangeli Marcello , Abe Yasuhiko , Aoyama Nobuo , Asonuma Kunio , Endo Yutaka , Esaki Motohiro , Fujii Toshimitsu , Fukuda Katsuyuki , Hirai Fumihito , Hisanaga Yasuhiro , Horiki Noriyuki , Iguchi Mikitaka , Ishigami Keisuke , Ishiguro Yoh , Ito Hiroaki , Kakuta Yoichi , Kamikozuru Koji , Kato Jun , Kawanishi Teruki , Kobayashi Taku , Kuge Hiroyuki , Maemoto Atsuo , Masuda Tomoyuki , Matsuoka Katsuyoshi , Matsushima Kayoko , Matsushima Masashi , Motoya Satoshi , Nakai Katsuhiko , Nakajima Koichi , Nakamura Masanao , Nishida Atsushi , Nishikawa Takahiro , Nishimata Nobuaki , Ochiai Toshiaki , Ohmiya Naoki , Ohnishi Yoshifumi , Oka Shiro , Ozeki Keiji , Saito Daisuke , Saruta Masayuki , Sasaki Makoto , Shimizu Masahito , Sugimoto Ken , Sujino Tomohisa , Suzuki Takayoshi , Takatori Hajime , Takatsu Noritaka , Takedatsu Hidetoshi , Takeuchi Ken , Tanaka Hiroki , Tokito Satoki , Endo Toshiyuki , Toyokawa Tatsuya , Uenoyama Yoshito , Yamamoto Takatsugu , Yamamoto Takayuki , Yasuda Hiroshi , Yokoyama Kaoru , Derovs Aleksejs , Pukitis Aldis , Jonaitis Laimas , Kazenaite Edita , Pinzon Te Lourdes Lol-be , D'Haens Geert , Lutgens Maurice , Brooker James , Gearry Richard , Griffiths Ben , Inns Stephen , Schultz Michael , Eszyk Jerzy , Kierkus Jaroslaw , Kleczkowski Dariusz , Kopon Adam , Petryka Robert , Regula Jaroslaw , Romanczyk Tomasz , Rydzewska-Wyszkowska Grazyna , Sikorski Piotr , Talarek Michal , Cerqueira Rute , Goncalves Tiago , Lopes Susana , Ministro Paula , Portela Francisco , Tavares Helena , Diculescu Mihai-Mircea , Goldis Adrian , Seicean Andrada , Agafina Alina , Edin Anton , Gerasimova Evgenia , Gettueva Maryana , Kashnikov Vladimir , Pirmagomedov Albert , Rafalskiy Vladimir , Sharapova Ksenia , Smolyarchuk Elena , Varganova Daria , Grgov Sasa , Jovanovic Igor , Svorcan Petar , Tarabar Dino , Ling Khoon Lin , Balaz Jozef , Durina Juraj , Gregus Milos , Laclav Martin , Drobne David , Deetlefs Eduan , Peter Jonny , Rajabally Muhammad , Rosa Jennifer , van Zyl Jan , Wright John , Cheon Jae Hee , Jang Byung Ik , Kim Jee Hyun , Kang Sang-Bum , Kim Dukhwan , Kim Tae Oh , Kim Young-Ho , Lee Jonghun , Lee Kang-Moon , Park Dong Il , Song Geun Am , Arguelles Arias Federico , Castro Laria Luisa , Echarri Piudo Ana , Garcia Lopez Santiago , Hernandez Ramirez Vincent , Martin Arranz Maria Dolores , Varela Trastoy Pilar , Vera Mendoza Maria , Lordal Mikael , Biedermann Luc , Misselwitz Benjamin , Chang Chung-Hsin , Chou Jen-Wei , Kuo Chia-Jung , Lin Ching-Pin , Tu Chia-Hung , Alkim Huseyin , Erzin Yusuf , Soykan Irfan , Kravchenko Tetiana , Tsarynna Nataliia , Vyshyvanyuk Vira , Ahmad Tariq , Cummings Fraser , Kapur Kapil , Kaser Arthur , Kent Alexandra , Parkes Gareth , Patel Kamal , Speight Richard , Steel Alan , Aberra Faten , Aguilar Humberto , Al Bawardy Badr , Ananthakrishnan Ashwin , Barnes Matthew , Beck Kendall , Berkelhammer Charles , Boland Brigid , Bullock Jeff , Chiplunker Adeeti , Dalal Robin , Dalal Sushila , Delgado Belkis , DiGiovanna Michael , DuVall George Aaron , Freedland Curtis , Friedenberg Keith , Gaidos Jill , Ginsburg Philip , Hassanein Tarek , Higgins Peter , Hong John , Hou Jason , Huilgol Vivek , Inamdar Nikhil , Kapur Saurabh , Kerman David , Levine Henry , Lodhia Nilesh , Loftus Edward , Mayoral Jaime , McNeil Donald , Melmed Gil , Mushahwar Andria , Ojeas Harry , Patel Bhaktasharan , Phillips Raymond , Pouzar Joe , Sarles Harry , Schock Joel , Sedghi Shahriar , Shah Nirav , Siddiqui Junaid , Stokesberry David , Su Le-Chu , Swaminath Arun , Verma Dharmendra , Weber John , Younes Ziad , Zisman Timothy 
Published: July 2024

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 &amp;lt; .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 &amp;lt; .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