The Efficacy and Safety of Guselkumab Induction Therapy in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 QUASAR Induction Study

Guselkumab is a fully human monoclonal antibody that binds to IL-23.¹ The anti-body is approved for the treatment of plaque psoriasis and psoriatic arthritis and is under investigation in inflammatory bowel disease. The phase 3 QUASAR study investigated the safety and efficacy of guselkumab induction therapy in patients with moderately to severely active UC.² The double-blind, parallel-group, multicenter, randomized, placebo-controlled trial enrolled patients who had had an inadequate response to or could not tolerate conventional and/or advanced therapies. Patients were required to have a modified Mayo score of 5 to 9, a rectal bleeding score of 1 or lower, and an endoscopy subscore no higher than 2. Patients were randomized 3:2 to receive intravenous guselkumab (200 mg) or placebo at weeks 0, 4, and 8. The primary endpoint was clinical remission at week 12, defined as a Mayo stool frequency subscore of 0 or 1 with no increase from baseline, a rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability.

The trial randomized 701 patients with a mean age of 40.5 years and a mean duration of UC of 7.5 years. The mean modified Mayo score was 6.9. Severe disease, indicated by a Mayo endoscopy subscore of 3, was observed in more than two-thirds (67.9%) of the study population. The trial met its primary endpoint, demonstrating clinical remission rates of 22.6% with guselkumab and 7.9% with placebo at week 12 (P<.001; Figure 6). In a comparison of the guselkumab arm and the placebo arm at week 12, the rates of symptomatic remission were 49.9% vs 20.7% (P<.001) and the rates of clinical response were 61.5% vs 27.9% (P<.001), respectively. Also at week 12, the rate of endoscopic improvement with guselkumab was superior to the rate with placebo (26.8% vs 11.1%; P<.001), as was the rate of histologic-endoscopic improvement (23.5% vs 7.5%; P<.001).

Figure 6.

Comparison of the proportions of patients in clinical remission at week 12 treated with guselkumab or placebo. Adapted from Allegretti et al. Abstract 913b. Presented at: DDW 2023; May 6-9, 2023; Chicago, Illinois.²

Safety data were consistent with the known safety profile of guselkumab observed in patients with the approved indications.³ In a comparison of the guselkumab and placebo arms, the rates of serious AEs were 2.9% vs 7.1% and the rates of AEs leading to discontinuation of study therapy were 1.7% vs 3.9%, respectively. Approximately 15% to 16% of patients in each arm experienced infection of any grade, with serious infection rates of less than 1% in each arm. AEs within 1 hour of infusion were observed in 1.4% of patients in the guselkumab arm and in 0.4% in the placebo arm, none of which were serious.