P1141 Guselkumab efficacy and safety in East Asian participants with moderate to severely active Ulcerative Colitis: Subgroup analysis of the Phase 2b/3 QUASAR induction and maintenance studies
Authors: Chen B , Ye B D , Cao Q , Hirai F , Saruta M , Chen M , Pelak S , Shipitofsky N , Wahking B , Zhuo J , Hisamatsu T 
Published: January 2025

Abstract

Background
The global QUASAR studies demonstrated efficacy and safety of guselkumab (GUS), a dual-acting interleukin-23p19 subunit inhibitor, as induction and maintenance therapy in participants (pts) with moderately to severely active ulcerative colitis (UC).1-3 We report a subgroup analysis in East Asian pts.

Methods
The QUASAR Ph 2b/3 clinical development programme for GUS in UC (NCT04033445) included adults with moderately to severely active UC (induction baseline modified Mayo score ≥5 to ≤9) with inadequate response/intolerance to conventional and/or advanced UC therapy. Two placebo (PBO)-controlled, 12-week studies evaluated intravenous (IV) GUS induction therapy: a Phase (Ph) 2b dose-ranging study (GUS 200 mg or 400 mg every 4 weeks [q4w]) and a Ph3 confirmatory study (GUS 200 mg q4w) (Figure 1). Pts from either study who were in clinical response at induction Week (W) 12 were re-randomised (1:1:1) at start of the maintenance study to subcutaneous (SC) GUS 200 mg q4w, GUS 100 mg q8w, or PBO. Primary endpoints were clinical response (Ph2b) or clinical remission (Ph3) at induction W12 and clinical remission at maintenance W44. This subgroup analysis included pts from QUASAR study sites located in East Asia (China, Japan, Korea, and Taiwan).

Results
This analysis included 71 (Ph2b: China, n=11; Japan, n=36; Korea, n=18; Taiwan, n=6) and 135 (Ph3: China, n=61; Japan, n=58; Korea, n=13; Taiwan, n=3) East Asian pts from the induction studies and 106 East Asian pts (China, n=34; Japan, n=52; Korea, n=13; Taiwan, n=7) who responded to IV GUS induction and participated in the maintenance study. At induction W12, higher proportions of pts in the IV GUS cohorts achieved clinical response and clinical remission relative to PBO pts (Figure 2A). At maintenance W44, higher proportions of pts achieved clinical remission and other meaningful clinical, patient-reported outcome, and endoscopic endpoints, including endoscopic normalisation, with both SC GUS maintenance dose regimens compared with PBO (Figure 2B).
Safety results were consistent with the overall population. Frequencies of pts with treatment-emergent adverse events (TEAEs) were generally consistent with rates reported in the overall global population in the maintenance study through W44. No cases of death, active tuberculosis, opportunistic infections, or anaphylactic or serum sickness-like reactions were reported.

Conclusion
Efficacy of GUS as IV induction and SC maintenance therapy in the subgroup of East Asian pts from QUASAR was consistent with that observed in the global study population. The safety profile of GUS was also favourable and consistent with previous reports.
This study was supported by Janssen Scientific Affairs, LLC.

References
1.Peyrin-Biroulet L, Allegretti JR, Rubin DT, et al. Gastroenterology. 2023;165(6):1443-1457.
2.Allegretti JR, Peyrin-Biroulet L, Feagan BG, et al. Gastroenterology. 2023;164(6):S-1572.
3.Rubin DT, Allegretti JR, Panés J, et al. Gastroenterology. 2024;166(5 Suppl.): S-180.