The Efficacy and Safety of Guselkumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Phase 2b QUASAR Study Results Through Week 12

The randomized, double-blind phase 2b QUASAR Induction Study 1 evaluated the safety and efficacy of12 weeks of guselkumab in patients with moderately to severely active ulcerative colitis.¹ The trial enrolled patients previously treated with conventional or advanced therapy that was intolerable or inadequate. Their Mayo rectal bleeding score was 1 or higher at baseline and their Mayo endoscopy subscore was at least 2, based on central review. The patients were randomly assigned to receive placebo, guselkumab at 200 mg every 4 weeks, or guselkumab at 400 mg every 4 weeks. The primary endpoint was the clinical response at week 12.

Among the entire study population of 313 patients, the median age was 41.6±14.40 years, and 59.1% were male. The mean duration of ulcerative colitis was 7.55±6.79 years. The mean Mayo score was 9.2±1.32, and the mean modified Mayo score was 7.0±1.0. Seventy percent of patients had a modified Mayo score of 7, 8, or 9, and 70% of patients had an endoscopy subscore of 3, indicating severe disease. Medications in use at baseline included oral aminosalicylates (77.3%), oral corticosteroids (39.6%), and immuno-suppressants (21.7%), and 23.3% of patients were intolerant to 2 or more classes of advanced therapy.

Nine patients (2.9%) discontinued treatment, most commonly owing to study withdrawal (1.0%) or worsening ulcerative colitis (1.0%). Results with the 2 doses of guselkumab were generally comparable. At week 12 of induction, the proportion of patients with a clinical response was 27.6% with placebo, 61.4% with the lower dose of guselkumab, and 60.7% with the higher dose of guselkumab (P<.001 for both; Figure 11). Rates of clinical remission were 9.5% with placebo vs 25.7% with the lower dose of guselkumab and 25.2% with the higher dose of guselkumab (P<.05 for both). The rates of symptomatic remission were 50.5% with the lower dose of guselkumab, 47.7% with the higher dose, and 20% with placebo (P<.001 for both). The rate of endoscopic improvement was 30.7% (P<.05 vs placebo), 30.8% (P<.001 vs placebo), and 12.4%, respectively. The rate of histo-endoscopic improvement at week 12 was 19.8% (P<.05 vs placebo) with the lower dose of guselkumab, 27.1% (P<.001 vs placebo) with the higher dose, and 8.6% with placebo. The rate of endoscopic normalization was also significantly worse with placebo (6.7%) compared with the lower dose of guselkumab (19.8%; P<.05 vs placebo). The comparison did not reach statistical significance with the higher dose of guselkumab (14.0%; P>.05 vs placebo).

Figure 11.

Clinical response at week 12 in the phase 2b QUASAR study, which evaluated induction therapy with guselkumab in patients with moderately to severely active ulcerative colitis. ^a Nominal P value <.001. IV, intravenous. Adapted from Dignass A et al. ECCO abstract OP32. J Crohns Colitis. 2022;16(suppl 1).¹

Safety results were generally consistent with observations from previous studies in approved indications. The rate of serious AEs was 1% in the guselkumab arms vs 5.7% in the placebo arm. AEs required treatment discontinuation in 0.5% vs 1.9%, respectively. The rate of infection was 10.6% vs 11.4%, with serious infections occurring in 0% vs 1.9%. No deaths occurred during the study.