S1685 Maintenance of Endoscopic and Histologic Efficacy With Guselkumab for Ulcerative Colitis at Week 92 of the QUASAR Long-Term Extension Study

Introduction: Guselkumab (GUS) is a dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23. In the QUASAR studies, GUS intravenous (IV) induction and subcutaneous (SC) maintenance demonstrated symptomatic, endoscopic, and histologic efficacy through 2 years. Here, we describe maintenance of endoscopic and histologic efficacy in the long-term extension (LTE). Methods: At maintenance week (W) 0, GUS IV induction responders were randomized 1:1:1 to GUS 100 mg SC every 8 weeks (every 8 weeks), GUS 200 mg SC every 4 weeks or placebo (GUS withdrawal). Participants (pts) completing the W44 visit could enter the LTE and continue the treatment regimen they were receiving at W44. Placebo pts discontinued after study unblinding. Efficacy data for randomized pts who continued to receive their GUS regimen assigned at W0 in the LTE were analyzed using 2 methods: 1) nonresponder imputation (NRI) accounting for pts with treatment failure or missing data, and 2) “as observed.” Results: Overall, 303 randomized pts (155 for 100 mg every 8 weeks and 148 for 200 mg every 4 weeks) continued their GUS treatment assigned at W0 in the LTE. Of pts who achieved endoscopic improvement at W44, 87.2% of GUS 100 mg every 8 weeks pts and 80.2% GUS 200 mg every 4 weeks pts maintained endoscopic improvement through W92 (NRI analysis). Of pts who achieved histologic improvement at W44, 77.9% and 75.2%, respectively, maintained histologic improvement at W92. Of pts who achieved histo-endoscopic mucosal improvement (HEMI) at W44, 73.5% and 75.5%, respectively, maintained HEMI through W92. Of pts who were in histologic remission at W44, 71.2% maintained histologic remission at W92 in both GUS groups. Results of the as-observed analysis were consistent with the NRI analysis; the dropout rate was low among GUS-treated pts in the LTE. Conclusion: High rates of long-term sustained endoscopic and histologic endpoints were observed at W92 of the LTE with both GUS dose regimens.