THE EFFICACY AND SAFETY OF GUSELKUMAB AS MAINTENANCE THERAPY IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 3 QUASAR MAINTENANCE STUDY

INTRO
The Phase 3 QUASAR Maintenance Study (NCT04033445) is a randomized-withdrawal, double-blind, placebo(PBO)-controlled, study that evaluated the efficacy and safety of maintenance treatment with subcutaneous (SC) guselkumab (GUS), an IL-23p19 subunit antagonist, in patients (pts) with moderately to severely active ulcerative colitis (UC) who had prior inadequate response or intolerance to conventional or advanced therapy (ADT) and demonstrated a clinical response to GUS IV induction (Figure1).
METHODS
At maintenance baseline, GUS IV induction Week (Wk)12 responders and PBO→GUS IV induction Wk24 responders were randomized 1:1:1 to SC GUS 200mg q4w, GUS 100mg q8w, or PBO(GUS withdrawal). The primary endpoint was clinical remission at Wk44. Major secondary endpoints included corticosteroid-free clinical remission, maintenance of clinical remission, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, IBDQ remission, and fatigue response at Wk44.
RESULTS
The primary analysis population included 568pts (mean age, 40.7yr; mean UC duration, 7.8yr; mean modified Mayo score, 6.9 [63.9% with severe disease]; Mayo endoscopy subscore of 3, 66.4%; baseline oral corticosteroid use, 40.0%). Approximately 42% had prior inadequate response or intolerance to ADT (TNF antagonists, vedolizumab, or tofacitinib), and 42.5% of these pts failed ≥2 ADT classes. Disease characteristics were similar across treatment groups at induction and maintenance baseline. With both GUS SC maintenance regimens, a significantly higher proportion of pts achieved the primary endpoint and all major secondary endpoints at Wk44 compared with PBO (Figure2). The proportion of pts with ≥1 adverse events(AEs) was similar across treatment groups: GUS 200mg q4w, 70.0%; GUS 100mg q8w, 64.5%, and PBO, 68.2%. The most common AEs in the combined GUS group vs PBO were COVID-19 (11.2% vs 14.1%), UC(11.2% vs 29.7%), and arthralgia (6.1% vs 6.8%), respectively. No cases of death, active tuberculosis, opportunistic infection, anaphylaxis, serum sickness, Hy’s Law, or serious hepatic AEs were reported. Two cases of malignancy (clear cell renal carcinoma, rectal adenocarcinoma) and 1 major adverse cardiovascular event (hemorrhagic stroke) were reported among GUS-treated pts (primary safety population).
CONCLUSION
Among pts with moderately to severely active UC who responded to GUS IV induction, maintenance therapy with both GUS SC regimens was safe and efficacious. The primary endpoint of clinical remission and all 9 major secondary endpoints across clinical, symptomatic, endoscopic, histologic, and patient-reported outcome measures were met with statistical significance by both GUS SC maintenance regimens. Safety results through maintenance Wk44 were consistent with the known and favorable safety profile of GUS in approved indications.