S1689 Intravenous and Subcutaneous Guselkumab Induction Therapy Are Both Efficacious in Crohn’s Disease Patients With High Baseline Disease Severity: Results at Week 12 From the Phase 3 GALAXI and GRAVITI Studies

Introduction: The comparable efficacy and safety of both intravenous (IV) and subcutaneous (SC) induction with guselkumab (GUS), a dual-acting IL-23p19 subunit inhibitor, in participants (pts) with moderately to severely active Crohn’s disease (CD) has been established in the phase 3 GALAXI and GRAVITI studies. To determine whether pts with higher baseline disease severity respond differently to IV or SC induction, we compared the efficacy of GUS IV and SC induction in subgroups based on baseline disease characteristics. Methods: Pts had moderately to severely active CD (CDAI 220-450 and SES-CD ≥6 or if ileal disease only, SES-CD ≥4), and a history of inadequate response/intolerance to oral corticosteroids, azathioprine/6-mercaptopurine/methotrexate, or biologics. GUS induction regimen was 200 mg IV every 4 weeks in GALAXI 2 & 3 (N = 582) and 400 mg SC every 4 weeks in GRAVITI (N = 230), while matching IV/SC PBO every 4 weeks (N = 148 and N = 117, respectively) was the comparator regimen. Clinical remission (CDAI <150) and endoscopic response (≥50% improvement from baseline SES-CD) were evaluated at Week 12 for predefined subgroups based on baseline involved disease location (ie, ileum, colon, or both), CDAI (ie, ≤300 or >300), SES-CD (ie, ≤12 or >12), fecal calprotectin (ie, ≤250 μ/g or >250 μ/g), and C-reactive protein (ie, >3 mg/L or ≤3 mg/L and >5 mg/L or ≤5 mg/L in GALAXI and GRAVITI, respectively). Abnormal C-reactive protein was defined as >3 mg/L and >5 mg/L for GALAXI and GRAVITI, respectively. Results: GALAXI and GRAVITI had similar eligibility criteria, and baseline disease characteristics of the randomized study populations were also similar. Pts treated with IV or SC GUS induction achieved clinical remission at Week 12 in greater proportions than those who received PBO across all subgroups. Endoscopic response at Week 12 was also achieved by greater proportions of GUS- than PBO-induced pts across all subgroups with either IV or SC induction. Conclusion: Both IV and SC induction with GUS were similarly effective in pts with moderately to severely active CD across predefined subgroups of disease location and baseline clinical, endoscopic, and inflammatory biomarker disease activity. The treatment effects were consistent in the subgroups following IV and SC induction, particularly in those that represent high disease severity.