Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies Lancet. 2025 Jan 4;405(10472):33-49. doi: 10.1016/S0140-6736(24)01927-5.Epub 2024 Dec 17. David T Rubin 1, Jessica R Allegretti 2, Julián Panés 3, Nicole Shipitofsky 4, Shadi S Yarandi 4, Kuan-Hsiang Gary Huang 4, Matthew Germinaro 4, Rebbecca Wilson 4, Hongyan Zhang 4, Jewel Johanns 4, Brian G Feagan 5, Tadakazu Hisamatsu 6, Gary R Lichtenstein 7, Brian Bressler 8, Laurent Peyrin-Biroulet 9, Bruce E Sands 10, Axel Dignass 11; QUASAR Study Group Collaborators
Orest Abrahamovych, Niazy Abu-Farsakh, Halyna Afanasieva, Hale Akpinar, Houssam Al Kharrat, Engin Altintas, Romain Altwegg, Pavel Andreev, Kazuki Aomatsu, Hiroshi Araki, Marjorie Argollo, Federico Ariel, Alessandro Armuzzi, Toshifumi Ashida, Monika Augustyn, Guy Aumais, Martín Azum, Filip Baert, Jozef Balaz, Domingo Balderramo, Jakob Begun, Temenuzhka Berova, Lore Billiauws, Antonio Blanco, Martin Bortlik, Fabrizio Bossa, Elena Bunkova, Mercedes Cabello, Qian Cao, Flavio Caprioli, Rute Cerqueira, Karen Chachu, Patrick Chamouard, Chunxiao Chen, Yan Chen, Baili Chen, Dongfeng Chen, Hong Chen, Youxiang Chen, Chou-Chen Chen, Jaehee Cheon, Minhu Chen, Cheng-Tang Chiu, Changhwan Choi, Elizabeth Chow, Michele Cicala, Aderson Cintra, Wit Danilkiewicz, Olena Datsenko, Gert De Hertogh, Julio De María, Leyanira Del Valle Torrealba Medina, Liu Deliang, Pierre Desreumaux, Pieter Dewint, Shigang Ding, Glen Doherty, Raina Draganova, Joris Dutré, George Duvall, Laurence Egan, Julien Fahed, Lars Fechner, Miroslav Fedurco, Aykut Ferhat Celik, Juan Fernandez, Rafal Filip, Sigal Fishman, Cristina Flores, Ronald Fogel, Sharyle Fowler, Carlos Francesconi, Toshimitsu Fujii, Mikihiro Fujiya, Masayuki Fukata, Seiichiro Fukuhara, Yohei Furumoto, Gyula G Kiss, Waldemar Gachowski, Xiang Gao, Antonio Gasbarrini, Beata Gawdis-Wojnarska, Daniel Gaya, Andrea Geccherle, Cyrielle Gilletta De Saint Joseph, Edgardo Gimenez, Paolo Gionchetti, Eran Goldin, Oleksandr Golovchenko, Maciej Gonciarz, Can Gonen, Chad Gonzales, Raquel Gonzalez, Gaston Julian Gonzalez Segura, Oleksiy Gridnyev, Fang Gu, Nitin Gupta, Tibor Gyokeres, Melissa Haines, Xavier Hebuterne, Charlotte Hedin, Per Hellstrom, Ida Normiha Hilmi, Fumihito Hirai, Takashi Hisabe, Tibor Hlavaty, Frank Hoentjen, Gerald Holtmann, Noriyuki Horiki, Ivo Horny, Gyula Horvat, Frantisek Horvath, Namiko Hoshi, Shuhei Hosomi, Ihor Hospodarskyy, Xiaohua Hou, Ludek Hrdlicka, Naizhong Hu, Vivian Huang, Caibin Huang, Tomoki Inaba, Yoh Ishiguro, Shunji Ishihara, Takeshi Ishikawa, Heba Iskandar, Eran Israeli, Soichi Itaba, Olha Ivanishyn, Ferenc Izbéki, Animesh Jain, Vipul Jairath, Byung Ik Jang, Chunmeng Jiang, Michael Jones, Takashi Kagaya, Dilara Kalimullina, Marina Karakina, Ali Karatas, Hiroshi Kashimura, Dan Keret, Yaroslava Khovaeva, Jaroslaw Kierkus, Taeoh Kim, Youngho Kim, Hyo Jong Kim, Jochen Klaus, Dariusz Kleczkowski, Maria Klopocka, Taku Kobayashi, Iwona Kobielusz-Gembala, Yuichiro Kojima, Ja Seol Koo, Adam Kopon, James Kopp, Fumikazu Koyama, Vasil Koynarski, Tetiana Kravchenko, Masatoshi Kudo, Ryusaku Kusunoki, Kwangan Kwon, Martin Laclav, Paula Lago, David Laharie, Juan Lasa, Syed Lateef, Tatjana Latinovic Radakovic, Kang Moon Lee, Jaroslaw Leszczyszyn, Yan Li, Mei Liu, Eashen Liu, Triana Lobaton Ortega, Denis Lopatin, Susana Lopes, Mileva Lovric Jovanovic, Marcio Lubini, Milan Lukas, Christian Maaser, Evzen Machytka, Atsuo Maemoto, Fernando Magro, Jorge Marcet, Eduardo Marini, Hiroyuki Marusawa, Jan Matous, Takayuki Matsumoto, Shoba Mendu, Yinglei Miao, Emese Mihaly, Pal Miheller, Paula Ministro, Hideharu Miyabayashi, Wolfgang Mohl, Martin Molnar, Gregory Moore, Gabriela Moran Faienzo, Eugeni Domenech Morral, Satoshi Motoya, Narayanachar Murali, Nazri Mohamad Mustaffa, Mohamed Naem, Katsuhiko Nakai, Koichi Nakajima, Yasunari Nakamoto, Masanao Nakamura, Stephane Nancey, Udayakumar Navaneethan, Khairul Najmi Muhammad Nawawi, Tomoyuki Ninomiya, Janos Novak, Motoji Oki, Genoile Oliveira Santana, Michio Onizawa, Yohei Ono, Taro Osada, Marina Osipenko, Danuta Owczarek, Jose Miguel Parente, Kamal Patel, Bhaktasharan Patel, Peder Pedersen, Rima Petroniene, Asen Petrov, Elina Petrova, Marie-Astrid Piquet, Juris Pokrotnieks, Elena Poroshina, Francisco Portela, Jatinder S Pruthi, Lyudmila Prystupa, Aldis Pukitis, Yun Qiu, Vladimir Rafalsky, Tova Rainis, Odery Ramos Junior, Mohammed Rashid, Yasser Rayyan, Olga Reshetko, Tarsila Ribeiro, Montserrat Rivero, Xavier Roblin, Jacek Romatowski, David Rowbotham, Orlando Enrique Ruffinengo, Grazyna Rydzewska-Wyszkowska, Oleg Sablin, Souken Sai, Simone Saibeni, Rosaida Hj Md Said, Hirotake Sakuraba, Mark Samaan, William Sandborn, Masayuki Saruta, Jenny Sauk, Edoardo Vincenzo Savarino, Michael Schultz, Joerg Schulze, Shahriar Sedghi, Ursula Seidler, Philippe Seksik, Omer Senturk, Edward Shelton, Masahito Shimizu, Sungjae Shin, Richa Shukla, Michael Sigal, Roberto Silva Junior, Joaquim Simoes Neto, Milan Siroky Jr, Vit Smajstrla, Vaclav Smid, Sarah Smiley, Luciana Soledad Brunatto, Mykola Stanislavchuk, David Stokesberry, Christian Stone, Daniel Suiter, Takayoshi Suzuki, Petar Svorcan, Sho Takagi, Tomohisa Takagi, Masaaki Takamura, Tetsuji Takayama, Ken Takeuchi, Akihito Tanaka, Hiroki Tanaka, Omar Tanash, Wen Tang, Ludmila Tankova, Luciana Teixeira Campos, Lena Thin, Alexander Tkachev, Ivars Tolmanis, Nataliia Tsarynna, Nikolay Tsonev, Zsolt Tulassay, Tetsuya Ueo, Nalan Unal, Ekaterina Valuyskikh, Willemijn Van Dop, Olga Vasilevskaya, Kannan Venugopal, Bram Verstockt, Manuel Viamonte, Vira Vyshyvanyuk, Bangmao Wang, Xiaoyan Wang, Jiangbin Wang, Yufang Wang, Shu-Chen Wei, Roni Weisshof, Sbeit Wisam, Katarzyna Wojcik, Alexey Yakovlev, Hiroshi Yasuda, Byongduk Ye, Hsu-Heng Yen, Hasan Yilmaz, Yoko Yokoyama, Hyuk Yoon, Takeshi Yoshida, Andriy Yurkiv, Osamu Zaha, Cyrla Zaltman, Qiang Zhan, Hongjie Zhang, Shutian Zhang, Lanxiang Zhu, Duowu Zou, Xiaoping Zou, Firas Zureikat |
Author information 1University of Chicago Medicine Inflammatory Bowel Disease Centre, Chicago, IL, USA. Electronic address: drubin@medicine.bsd.uchicago.edu. 2Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 3Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain. 4Janssen Research and Development, Spring House, PA, USA. 5Western University, London, ON, Canada. 6Kyorin University, Tokyo, Japan. 7University of Pennsylvania, Philadelphia, PA, USA. 8University of British Columbia, Vancouver, BC, Canada. 9University of Lorraine, Inserm, NGERE, F-54000 Nancy, France and Groupe Hospitalier privé Ambroise Paré-Hartmann, Paris IBD Centre, Neuilly-sur-Seine, France. 10Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 11Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt, Germany. Abstract Background: Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis. Methods: The primary populations of these two phase 3, randomised, double-blind, placebo-controlled studies (QUASAR phase 3 induction and maintenance) included randomised and treated adults with moderately to severely active ulcerative colitis (induction baseline modified Mayo score from 5 to 9) with inadequate response or intolerance to conventional or advanced ulcerative colitis therapy. Patients were randomly assigned (3:2) to receive guselkumab 200 mg given intravenously or placebo at weeks 0, 4, and 8 (phase 3 induction study). All patients were randomly assigned using web-based interactive response technology. Patients in clinical response 12 weeks after guselkumab induction given intravenously (from QUASAR phase 2b and phase 3 induction studies) were randomly assigned (1:1:1) at maintenance week 0 to guselkumab 200 mg given subcutaneously every 4 weeks or 100 mg every 8 weeks or placebo for 44 weeks (maintenance). Primary endpoints were clinical remission at induction week 12 and maintenance week 44. This study is registered with ClinicalTrials.gov, NCT04033445. Findings: The induction study primary population included 701 patients (guselkumab 200 mg given intravenously 60% [421 patients]; placebo 40% [280 patients]). The maintenance study primary population included 568 guselkumab induction responders randomly assigned to receive guselkumab 200 mg given subcutaneously every 4 weeks (190 [33%] patients) or 100 mg every 8 weeks (188 [33%] patients) or placebo (guselkumab withdrawal 190 [33%] patients). A significantly greater proportion of patients treated with guselkumab given intravenously had clinical remission at induction week 12 (23% [95 of 421 patients]) than did placebo-treated patients (8% [22 of 280 patients]; adjusted treatment difference 15%, 95% CI 10-20; p<0·0001). Clinical remission at maintenance week 44 was achieved by a significantly greater proportion of patients treated with guselkumab 200 mg given subcutaneously every 4 weeks (50% [95 of 190 patients]; adjusted treatment difference 30%, 95% CI 21-38; p<0·0001) and 100 mg every 8 weeks (45% [85 of 188 patients]; adjusted treatment difference 25%, 16-34; p<0·0001) than with placebo (19% [36 of 190 patients]). The overall safety profile was favourable and consistent with that of guselkumab in approved indications. In the induction study, adverse events were reported by 49% of patients in both groups (208 of 421 guselkumab-treated patients and 138 of 280 placebo-treated patients), serious adverse events were reported by 3% (12 of 421) of guselkumab-treated patients and 7% (20 of 280) of placebo-treated patients, and adverse events leading to treatment discontinuation were reported by 2% (seven of 421) of guselkumab-treated patients and 4% (11 of 280) of placebo-treated patients. In the maintenance study, adverse event rates were similar among groups, and the most frequently reported adverse events in all groups were ulcerative colitis, COVID-19, and arthralgia. No active tuberculosis, anaphylaxis, serum sickness, or clinically important hepatic disorders were reported in either study. Interpretation: Guselkumab was effective and safe as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. Funding: Janssen Research and Development. |
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