- Fecal Incontinence
|Guselkumab for the Treatment of Crohn's Disease: Induction Results From the Phase 2 GALAXI-1 Stud
Gastroenterology. 2022 May;162(6):1650-1664.e8.doi: 10.1053/j.gastro.2022.01.047. Epub 2022 Feb 5.
William J Sandborn 1, Geert R D'Haens 2, Walter Reinisch 3, Julián Panés 4, Daphne Chan 5, Susana Gonzalez 6, Kathleen Weisel 6, Matthew Germinaro 6, Mary Ellen Frustaci 6, Zijiang Yang 6, Omoniyi J Adedokun 6, Chenglong Han 7, Remo Panaccione 8, Tadakazu Hisamatsu 9, Silvio Danese 10, David T Rubin 11, Bruce E Sands 12, Anita Afzali 13, Jane M Andrews 14, Brian G Feagan 15, GALAXI-1 Investigators
1University of California-San Diego, La Jolla, California. Electronic address: firstname.lastname@example.org.
2Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
3Medical University of Vienna, Vienna, Austria.
4Hospital Clinic of Barcelona, August Pi i Sunyer Biomedical Research Institute, Biomedical Research Centers on Hepatic and Digestive Diseases, Barcelona, Spain.
5Janssen Scientific Affairs, LLC, Horsham, Pennsylvania.
6Janssen Research and Development, LLC, Spring House, Pennsylvania.
7Janssen Global Services, LLC, Malvern, Pennsylvania.
8University of Calgary, Calgary, Alberta, Canada.
9Kyorin University, Tokyo, Japan.
10Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
11University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, Illinois.
12Icahn School of Medicine at Mount Sinai, New York, New York.
13The Ohio State University, Wexner Medical Center, Columbus, Ohio.
14Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia.
15University of Western Ontario, London, Ontario, Canada.
Background & aims: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis. This study evaluated the efficacy and safety of guselkumab in patients with moderately to severely active Crohn's disease with inadequate response or intolerance to conventional or biologic therapy.
Methods: GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo. Change from baseline in Crohn's Disease Activity Index score (primary end point), clinical remission, clinical response, Patient Reported Outcomes-2 remission, clinical-biomarker response, endoscopic response (major secondary end points), and safety in guselkumab-treated patients vs placebo were evaluated through week 12. Ustekinumab was a reference arm.
Results: Of 309 patients evaluated, approximately 50% had disease refractory to prior biologic therapy. At week 12, significantly greater reductions in Crohn's Disease Activity Index from baseline (least squares means: 200 mg: -160.4, 600 mg: -138.9, and 1200 mg: -144.9 vs placebo: -36.2; all, P < .05) and significantly greater proportions of patients achieved clinical remission in each guselkumab group vs placebo (Crohn's Disease Activity Index <150; 57.4%, 55.6%, and 45.9% vs 16.4%; all, P < .05). Greater proportions of patients receiving guselkumab achieved clinical response, Patient Reported Outcomes-2 remission, clinical-biomarker response, and endoscopic response at week 12 vs placebo. Efficacy of ustekinumab vs placebo was also demonstrated. Safety event rates were generally similar across treatment groups.
Conclusions: At week 12, all 3 dose regimens of guselkumab induced greater clinical and endoscopic improvements vs placebo, with a favorable safety profile.
Clinicaltrials: gov, Number: NCT03466411.