Efficacy and Safety of Guselkumab Subcutaneous Induction and Maintenance in Participants with Moderately to Severely Active Crohn’s Disease: Results from the Phase 3 GRAVITI Study

IF 25.7 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gastroenterology Pub Date : 2025-03-18 DOI:10.1053/j.gastro.2025.02.033

Ailsa Hart, Remo Panaccione, Flavio Steinwurz, Silvio Danese, Tadakazu Hisamatsu, Qian Cao, Timothy Ritter, Ursula Seidler, Mobolaji Olurinde, Marion L. Vetter, Jacqueline Yee, Zijiang Yang, Yuhua Wang, Jewel Johanns, Chenglong Han, Aparna Sahoo, Natalie A. Terry, Bruce E. Sands, Geert D’Haens

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Abstract

Background and Aims

Subcutaneous (SC) induction and maintenance with guselkumab was evaluated in adult participants with moderately to severely active Crohn’s disease (CD).

Methods

The Phase 3 double-blind, placebo-controlled, treat-through GRAVITI study randomized 347 participants 1:1:1 to guselkumab 400mg SC q4w→100mg SC every 8 weeks (q8w) (n=115), guselkumab 400mg SC every 4 weeks (q4w)→200mg SC q4w (n=115), or placebo (n=117). Placebo participants meeting rescue criteria received guselkumab from week 16 onward. Co-primary endpoints were clinical remission at week 12 and endoscopic response at week 12. Additional multiplicity-controlled endpoints were Patient Reported Outcome-2 remission (week 12), clinical response (week 12), clinical remission (week 24), clinical remission (week 48), and endoscopic response (week 48). Safety was assessed through week 48.

Results

All multiplicity-controlled endpoints were met. At week 12, significantly greater proportions of participants receiving guselkumab 400mg achieved clinical remission versus placebo (56.1% vs 21.4%; Δ=34.9; p<0.001), and endoscopic response versus placebo (41.3% vs 21.4%; Δ=19.9; p<0.001). At week 48, significantly greater proportions of participants in both guselkumab groups (100mg SC q8w: 60.0%, Δ=42.8; 200mg SC q4w: 66.1%, Δ=48.9) achieved clinical remission versus placebo (17.1%; p<0.001 each) and endoscopic response (44.3%, Δ=37.5; 51.3%, Δ=44.6; versus placebo 6.8%; p<0.001 each). Efficacy was observed in both bionaive participants and those with inadequate response/intolerance to biologics. Adverse event rates were not greater in guselkumab groups versus placebo.

Conclusion

Subcutaneous guselkumab for both induction and maintenance was efficacious in treating participants with moderately to severely active CD. Safety findings were consistent with those of guselkumab in approved indications, including ulcerative colitis.

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来源期刊

Gastroenterology 医学-胃肠肝病学

CiteScore

45.60

自引率

2.40%

发文量

4366

审稿时长

26 days

期刊介绍： Gastroenterology is the most prominent journal in the field of gastrointestinal disease. It is the flagship journal of the American Gastroenterological Association and delivers authoritative coverage of clinical, translational, and basic studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. Some regular features of Gastroenterology include original research studies by leading authorities, comprehensive reviews and perspectives on important topics in adult and pediatric gastroenterology and hepatology. The journal also includes features such as editorials, correspondence, and commentaries, as well as special sections like "Mentoring, Education and Training Corner," "Diversity, Equity and Inclusion in GI," "Gastro Digest," "Gastro Curbside Consult," and "Gastro Grand Rounds." Gastroenterology also provides digital media materials such as videos and "GI Rapid Reel" animations. It is abstracted and indexed in various databases including Scopus, Biological Abstracts, Current Contents, Embase, Nutrition Abstracts, Chemical Abstracts, Current Awareness in Biological Sciences, PubMed/Medline, and the Science Citation Index.