DOP060 Early disease efficacy of guselkumab therapy in biologic-naïve patients with moderately to severely active Crohn’s disease: Post-hoc analysis from the phase 3 GALAXI 2 & 3 studies
Authors: Afzali A , Rubin D T , Danese S , Rayyan Y , Chen M , Terry N A , Salese L , Van Rampelbergh R , Yee J , Gomez M , Wan K Y Y , Yang Z , Sands B E , D'Haens G 
Published: January 2025

Abstract

Background
Early biologic treatment is associated with better outcomes in pts with CD. GALAXI 2 & 3 are identically designed trials assessing the efficacy and safety of guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in pts with moderately to severely active CD, and the efficacy in BIO-naïve pts was previously reported.1,2,3 Here, we present results of a post-hoc analysis of GUS efficacy in BIO-naïve pts with disease duration ≤2yrs using data from the pooled GALAXI trials.

Methods
Pts had moderately to severely active CD (based on CDAI and SES-CD) and a history of inadequate response/intolerance to oral corticosteroids (CS), AZA, 6-MP, MTX, or biologics. Pts were randomized 2:2:2:1 to GUS 200mg IV q4w (x3)→200mg SC q4w, GUS 200mg IV q4w (x3)→100mg SC q8w, ustekinumab (UST) ~6mg/kg IV (x1)→90mg SC q8w (active comparator), or placebo (PBO). PBO pts not in clinical response at W12 switched to UST. GUS vs PBO was evaluated for clinical response, clinical remission, and endoscopic response at W12 and patient-level composite endpoints of clinical response at W12 + clinical remission at W48 and clinical response at W12 + endoscopic response at W48. GUS vs UST was evaluated at W48 for endoscopic response and endoscopic remission, patient-level composite endpoints of clinical remission + endoscopic response and deep remission, and clinical remission (definitions in Table). All p-values were nominal.

Results
Of the 426 BIO-naïve pts in the pooled analysis, 180 had disease duration ≤2yrs. Greater proportions of pts treated with GUS 200mg IV than PBO achieved clinical response at W12 (67.3% vs 25.0%; Δ=42.3%; p&lt;0.001), clinical remission at W12 (51.0% vs 16.7%; Δ=30.8%; p=0.002), and endoscopic response at W12 (49.0% vs 29.2%; Δ=19.9%; p=0.058). Greater proportions of pts treated with either GUS 100mg SC or 200mg SC achieved clinical response at W12 + clinical remission at W48 and clinical response at W12 + endoscopic response at W48 vs PBO (Figure 1A). Compared to UST at W48 (Figure 1B), greater proportions of pts treated with either GUS 100mg SC or 200mg SC achieved endoscopic response, endoscopic remission, clinical remission + endoscopic response, and deep remission. High levels of clinical remission were achieved by GUS-treated pts at W48.

Conclusion
In GALAXI, GUS-treated BIO-naïve pts with disease duration ≤2yrs achieved clinical and endoscopic endpoints in greater proportions compared with PBO and endoscopic endpoints in greater proportions compared with UST. Overall, these robust results highlight the benefit of early biologic treatment and supports the use of GUS as an early therapeutic choice in CD.

References
1. Panaccione R, Danese S, Feagan BG, et al. Gastroenterology. 2024; 166(5): S1057b.
2. Sands BE, D’Haens G, Danese S, et al. United European Gastroenterol J. 2024; 12(S8): 43-4.
3. Danese S, Afzali A, Panaccione R, et al. United European Gastroenterol J. 2024; 12(S8): 622-4.