S1688 Effects of Subcutaneous Guselkumab Induction and Maintenance on Histologic Outcomes in Patients With Moderately to Severely Active Crohn’s Disease in GRAVITI, a Phase 3 Double-Blind, Placebo-Controlled, Treat-Through Study

Introduction: Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that was efficacious in double-blind, placebo-controlled, treat-through trials in participants (pts) with moderately to severely active Crohn’s disease (CD) using IV induction and SC maintenance (GALAXI 2 & 3) or SC induction and maintenance (GRAVITI). Assessment of histologic disease activity is becoming increasingly important as a measure of treatment efficacy. Here we report histologic outcomes at Weeks (W) 12 & 48 from GRAVITI. Methods: Pts were randomized 1:1:1 to GUS 400 mg SC every 4 weeks → 200 mg SC every 4 weeks, GUS 400 mg SC every 4 weeks → 100 mg SC every 8 weeks, or PBO. Biopsies were obtained from the most affected area (or if no disease activity present, normal-appearing mucosa) in 5 segments: terminal ileum, ascending colon, transverse colon, descending colon, and rectum. Histologic response, histologic remission, and the composite endpoints of histo-endoscopic response and histo-endoscopic remission were evaluated using Robarts Histopathology Index (RHI), Global Histologic Activity Score (GHAS), and Geboes scoring. Histologic response was assessed in pts with baseline histologic disease; histologic remission, histo-endoscopic response, and histo-endoscopic remission were assessed in the full analysis set. Pts who met rescue criteria at W16 were considered non-responders at W48. Histologic endpoints in GRAVITI were exploratory and not controlled for multiple comparisons; P-values are nominal. Results: Of the 347 pts in the full analysis set, 273 (78.7%) had baseline histologic disease per RHI score. SC induction with GUS (400 mg SC at W0, W4, & W8) resulted in greater rates of histologic response, histologic remission, histo-endoscopic response, and histo-endoscopic remission compared to placebo at W12. At W48, greater proportions of pts receiving GUS 100 mg SC every 8 weeks or GUS 200 mg SC every 4 weeks maintenance also achieved histologic response, histologic remission, histo-endoscopic response, and histo-endoscopic remission compared to PBO. Comparable outcomes were observed using GHAS or Geboes scoring criteria. Conclusion: Compared to PBO, pts with moderately to severely active CD receiving SC induction and maintenance treatment with GUS achieved greater rates of histologic response, histologic remission, histo-endoscopic response, and histo-endoscopic remission through W48. These results support the use of histologic and composite histologic and endoscopic endpoints as a measure of CD activity, and the efficacy of SC guselkumab in CD.