P0843 Efficacy by baseline disease characteristics of subcutaneous guselkumab induction therapy in patients with moderately to severely active Crohn’s disease: Results at Week 12 from the phase 3 GRAVITI study
Authors: D’Haens G , Hisamatsu T , Steinwurz F , Hart A , Liu W , Olurinde M , Ngqawa P , Yang Z , Merrall E , Terry N A , Sands B E , Panaccione R 
Published: January 2025

Abstract

Background
The GRAVITI study established the efficacy and safety of subcutaneous (SC) induction with guselkumab, a dual-acting IL-23p19 subunit inhibitor, in participants with moderately to severely active Crohn’s disease through 48 weeks of treatment.1 Here, we evaluated the efficacy of guselkumab SC induction in GRAVITI subgroups based on baseline disease characteristics.

Methods
Eligible participants had a history of inadequate response or intolerance to oral corticosteroids, azathioprine, 6-mercaptopurine, methotrexate, or biologics (ie, TNF antagonists or vedolizumab). Randomization was stratified by baseline CDAI, SES-CD, and history of inadequate response or intolerance to biologics, with 347 participants allocated 1:1:1 to guselkumab 400 mg SC q4w (x3) → guselkumab 200 mg SC q4w, guselkumab 400 mg SC q4w (x3) → guselkumab 100 mg SC q8w, or placebo. The co-primary endpoints assessed at Week 12 compared the combined guselkumab 400 mg SC group (N=230) to placebo (N=117). Clinical remission at Week 12 (CDAI&lt;150) and endoscopic response at Week 12 (≥50% improvement from baseline SES-CD) were evaluated for predefined subgroups based on disease duration in years (ie, ≤5, &gt;5 to ≤15, or &gt;15), involved disease location as assessed by central reader (ie, ileum, colon, or both), CDAI (ie, ≤300 or &gt;300), C-reactive protein (ie, ≤5 or &gt;5; CRP), fecal calprotectin (ie, ≤250 or &gt;250; FeCal), and SES-CD (≤12 or &gt;12).

Results
Clinical remission at Week 12 and endoscopic response at Week 12 were achieved by greater proportions of guselkumab- than placebo-treated participants across all subgroups (Figures 1 and 2). Treatment differences of guselkumab vs placebo for clinical remission at Week 12 were similar for each subgroup of disease duration, involved disease location, and FeCal. Guselkumab difference from placebo in clinical remission at Week 12 was greatest for participants with CRP&gt;5 vs CRP≤5 (adjusted treatment difference: 42.8% vs 24.7%) and participants with SES-CD&gt;12 vs SES-CD≤12 (adjusted treatment difference: 45.3% vs 28.2%). Treatment differences of guselkumab vs placebo for endoscopic response at Week 12 were similar for each subgroup of disease duration, involved disease location, CDAI score, CRP, FeCal, and SES-CD.

Conclusion
In GRAVITI, guselkumab SC induction was effective in inducing clinical remission at Week 12 and endoscopic response at Week 12 across predefined subgroups based on disease characteristics among participants with moderately to severely active Crohn’s disease.

References
1)Panaccione R, Hart A, Steinwurz F, 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. Presented at American College of Gastroenterology 2024.