P1030 Efficacy and safety of subcutaneous guselkumab in East Asian participants with moderately to severely active Crohn’s disease: Subgroup analysis of the Phase 3 GRAVITI study
Authors: Liu W , Guo H , Kim T O , Takeuchi K , Hisamatsu T , Fable J , Olurinde M , Wahking B , Zhuo J , Cao Q 
Published: January 2025

Abstract

Background
Guselkumab (GUS) is a dual-acting interleukin-23 p19 subunit inhibitor that was efficacious in phase 3 trials of participants (pts) with Crohn’s disease (CD) using either intravenous (IV; GALAXI 2/3) or subcutaneous (SC; GRAVITI) induction and SC maintenance.1,2 We evaluated the efficacy and safety of GUS SC induction and SC maintenance in a post hoc subgroup analysis of East Asian (China, Japan, Korea, and Taiwan) pts from GRAVITI, a phase 3 treat-through trial in pts with moderately to severely active CD.

Methods
The GRAVITI study (NCT05197049) included pts with CD with a history of inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics (BIO-IR). Randomization was stratified by baseline Crohn’s Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn’s Disease (SES-CD), and BIO-IR status, and pts were allocated 1:1:1 in a treat-through design to GUS 400mg SC every 4 weeks (q4w) (x3)→GUS 200mg SC q4w, GUS 400mg SC q4w (x3)→GUS 100mg SC every 8 weeks (q8w), or placebo (PBO). Participants in the placebo group who met rescue criteria received GUS 400mg SC at Wk16, Wk20, and Wk24 followed by GUS 100mg SC q8w; GUS pts stayed on GUS per treat-through design (sham rescue). The co-primary endpoints were clinical remission at Wk12 and endoscopic response at Wk12. Additional endpoints were patient-reported outcome 2 (PRO-2) remission at Wk12, clinical response at Wk12, clinical remission at Wk24, clinical remission at Wk48, and endoscopic response at Wk48. All endpoints assessed through Wk12 compared the combined GUS 400mg SC treatment arm to PBO; assessments after Wk12 compared each GUS SC maintenance regimen to PBO. All pts who met rescue criteria were considered not to have met efficacy endpoints after Wk16. Safety was assessed through Wk48.

Results
This analysis included 71 East Asian pts. At Wk12, higher proportions of pts in the GUS 400mg SC cohort achieved clinical remission, clinical response, endoscopic response, and PRO-2 remission relative to PBO pts. At Wk24 and Wk48, higher proportions of pts achieved clinical remission in both GUS SC maintenance dose regimens compared with PBO. Endoscopic response at Wk48 was achieved in a higher proportion of pts in both GUS SC maintenance dose regimens compared with PBO (Figure 1). Key safety event rates through Wk48 were similar among treatment groups (Table 1). No deaths were reported in East Asian pts.

Conclusion
Efficacy of GUS as SC induction followed by SC maintenance therapy in the subgroup of East Asian pts from GRAVITI was consistent with that observed in the overall study population. The safety profile was consistent with the known safety profile of GUS in approved indications and with the overall study population.

References
1.Panaccione R, Danese S, Feagan BG, et al. Efficacy and safety of guselkumab therapy in patients with moderately to severely active Crohn’s disease: results of the GALAXI 2 & 3 phase 3 studies. Gastroenterology. 2024;166(5 Suppl):1057b-1057b2
2.Panaccione R, Hart A, Steinwurz F, Danese S, Hisamatsu T, Cao Q, et al. Efficacy and safety of subcutaneous guselkumab induction therapy in patients with moderately to severely active Crohn’s disease: results through week 48 from the phase 3 GRAVITI study. Oral presentation 72. In: American College of Gastroenterology 2024 Annual Scientific Meeting; October 25-30, 2024; Philadelphia, PA, USA.