Lancet Gastroenterol Hepatol. 2024 Feb;9(2):133-146.doi: 10.1016/S2468-1253(23)00318-7. Epub 2023 Dec 14.

Silvio Danese ¹, Remo Panaccione ², Brian G Feagan ³, Anita Afzali ⁴, David T Rubin ⁵, Bruce E Sands ⁶, Walter Reinisch ⁷, Julián Panés ⁸, Aparna Sahoo ⁹, Natalie A Terry ⁹, Daphne Chan ¹⁰, Chenglong Han ⁹, Mary Ellen Frustaci ⁹, Zijiang Yang ⁹, William J Sandborn ¹¹, Tadakazu Hisamatsu ¹², Jane M Andrews ¹³, Geert R D'Haens ¹⁴; GALAXI-1 Study Group

GALAXI-1 Study Group: 

Oleksandr Oliinyk, Leonid Bilianskyi, Jadwiga Gniady-Jastrzebska, Robert Petryka, Tomasz Arlukowicz, Piotr Gietka, Marcin Zmudzinski, Syed Mumtaz, Douglas Wolf, Katarzyna Wojcik, George Duvall, Monika Augustyn, Rafal Filip, Dino Tarabar, Alexander Tkachev, Ursula Seidler, Eran Zittan, Juris Pokrotnieks, Oksana Shchukina, Andro Machavariani, Laura Loy, Niazy Abu-Farsakh, Pesegova Marina, Slobodan Sreckovic, Martin Laclav, Shu-Chen Wei, Daniel Suiter, Aleksey Borsuk, Xavier Hebuterne, Carsten Buning, Adi Lahat-Zok, Wit Danilkiewicz, Bernadetta Frysna, Ivana Jovicic, Olena Datsenko, Maninder Guram, Animesh Jain, Zahid Rashid, Sonja Heeren, Natallia Shulga, Ivan Timkin, Srdjan Gornjakovic, Milan Lukas, Romain Altwegg, Ariadne Desjeux, Jean-Marie Reimund, Manana Giorgadze, Christoph Jochum, Hiroaki Ito, Katsuhiko Nakai, Tomohisa Takagi, Osamu Zaha, Changhwan Choi, Taeoh Kim, Jonghun Lee, Ieva Stundiene, Ida Normiha Hilmi, Rosaida Hj Md Said, Jaroslaw Leszczyszyn, Diana Abdulganieva, Yulia Fominykh, Svetlana Maksyashina, Jozef Balaz, Manuel Van Domselaar, Taylan Kav, Patrick Dennis, Patricia Henry, Robert Holmes, Christopher Johnson, Matthew McBride, Harry Sarles, Gregory Moore, Ruslan Yakubtsevich, Vinciane Muls, Stevan Trbojevic, Waqqas Afif, Charles Bernstein, Ivo Klarin, Zuzana Serclova, Miroslava Volfova, Pierre Desreumaux, Cyrielle Gilletta de Saint Joseph, Xavier Roblin, Lucine Vuitton, Kakhaber Chelidze, Tanja Kuehbacher, Ioannis Koutroubakis, Michele Cicala, Walter Fries, Antonio Gasbarrini, Nobuo Aoyama, Yoshito Hayashi, Fumihito Hirai, Norkiyuki Horiki, Namiko Hoshi, Tomoki Inaba, Ishida Hiroyasu, Atsuo Maemoto, Takayuki Matsumoto, Kayoko Matsushima, Satoshi Motoya, Masaki Taruishi, Mohammed Rashid, Jaeyoung Chun, Young-Ho Kim, Dong Il Park, Ala Sharara, Laimas Jonaitis, Gjorgi Deriban, James Brooker, Beata Gawdis-Wojnarska, Barbara Wozniak-Stolarska, Pavel Andreev, Vladimir Simanenkov, Vasiliy Trofimov, Igor Jovanovic, Natasa Zdravkovic, Xavier Aldeguer I Mante, Vicent Hernandez Ramirez, Hale Akpinar, Gurkan Celebi, Hulya Hamzaoglu, Juan Fernandez, Jayaprakash Kamath, Nicole Palekar, Jatinder S Pruthi, David Rausher, Timothy Ritter

Author information

¹Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy. Electronic address: sdanese@hotmail.com.

²Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.

³Western University, London, ON, Canada.

⁴Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

⁵University of Chicago School of Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA.

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

⁷Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.

⁸Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

⁹Janssen Research & Development, Spring House, PA, USA.

¹⁰Janssen Scientific Affairs, Horsham, PA, USA.

¹¹Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA; Ventyx Biosciences, Encinitas, CA, USA.

¹²Department of Gastroenterology and Hepatology, Kyorin University, Tokyo, Japan.

¹³Department of Gastroenterology and Hepatology, Royal Adelaide Hospital and University of Adelaide, Adelaide, SA, Australia.

¹⁴Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, Netherlands.

Abstract

Background: Many patients with moderately to severely active Crohn's disease do not respond to available therapies or lose response over time. The GALAXI-1 study previously found that three intravenous guselkumab dosages showed superior clinical and endoscopic outcomes over placebo at week 12 in patients with moderately to severely active Crohn's disease. We report the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study.

Methods: We did a phase 2, randomised, multicentre, double-blind trial. Adult patients with moderately to severely active Crohn's disease were randomly allocated with a computer-generated randomisation schedule to receive one of five treatment groups, with regimens consisting of an intravenous induction phase transitioning to a subcutaneous maintenance phase starting at week 12 in a treat-through design: (1) guselkumab 200→100 mg group (200 mg intravenous at weeks 0, 4, and 8, then 100 mg subcutaneous every 8 weeks; (2) guselkumab 600→200 mg group (600 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (3) guselkumab 1200→200 mg group (1200 mg intravenous at weeks 0, 4, and 8, then 200 mg subcutaneous every 4 weeks); (4) ustekinumab group (approximately 6 mg/kg intravenous at week 0, then 90 mg subcutaneous every 8 weeks); or (5) placebo group (placebo induction followed by either placebo maintenance [for those with CDAI clinical response at week 12] or crossover to ustekinumab [for those without CDAI clinical response at week 12]). Endpoints assessed at week 48 included CDAI remission (CDAI score <150), endoscopic response (≥50% improvement from baseline in SES-CD or SES-CD score ≤2), and endoscopic remission (SES-CD score ≤2) in the primary efficacy analysis population of all randomised patients who received at least one dose of study drug, excluding those discontinued during a temporary study pause. Safety analyses included all randomised patients who received at least one study drug dose. This trial is registered at Clinical Trials.gov (NCT03466411) and is active but not recruiting.

Findings: Among 700 patients screened, 309 (112 biologic-naive; 197 biologic-experienced) were included in the primary efficacy analysis population: 61 in the guselkumab 200→100 mg group, 63 in the guselkumab 600→200 mg group, 61 in the guselkumab 1200→200 mg group, 63 in the ustekinumab group, and 61 in the placebo group. 126 (41%) women and 183 (59%) men were included, with median age 36·0 years (IQR 28·0-49·0). At week 48, the numbers of patients with CDAI clinical remission were 39 (64%) in the guselkumab 200→100 mg group, 46 (73%) in the guselkumab 600→200 mg group, 35 (57%) in the guselkumab 1200→200 mg group, and 37 (59%) in the ustekinumab group. The corresponding numbers of patients with endoscopic response were 27 (44%), 29 (46%), 27 (44%), and 19 (30%), respectively, and endoscopic remission was seen in 11 (18%), 11 (17%), 20 (33%), and four (6%) patients, respectively. In the placebo group, 15 patients were in CDAI clinical response at week 12 and continued placebo; of these, nine (60%) were in clinical remission at week 48. 44 patients in the placebo group were not in CDAI clinical response at week 12 and crossed over to ustekinumab; of these, 26 (59%) were in clinical remission at week 48. Up to week 48, adverse events frequencies in the safety population (n=360) were 46 (66%) of 70 patients (464·9 events per 100 patient-years of follow-up) in the placebo group, 163 (74%) of 220 patients (353·1 per 100 patient-years) in the three guselkumab groups combined, and 60 (85%) of 71 patients (350·7 per 100 patient-years) in the ustekinumab group. Among patients treated with guselkumab or ustekinumab, the most frequently reported infections up to week 48 were nasopharyngitis (25 [11%] of 220 guselkumab recipients, 12 [11%] of 114 ustekinumab recipients) and upper respiratory infections (13 [6%] guselkumab recipients, eight [7%] ustekinumab recipients). After week 12, one patient who responded to placebo induction and two guselkumab-treated patients had serious infections. No active tuberculosis, opportunistic infections, or deaths occurred.

Interpretation: Patients receiving guselkumab intravenous induction and subcutaneous maintenance treatment achieved high rates of clinical and endoscopic efficacy up to week 48. No new safety concerns were identified.

Funding: Janssen Research & Development.