Jessica R. Allegretti, MD, MPH

Credit: Brigham and Women's Hospital

Guselkumab resulted in a statistically greater percentage of patients with ulcerative colitis achieving clinical remission compared to placebo.

In data presented as a late-breaking abstract during the 2023 Digestive Disease Week (DDW) in Chicago, a team, led by Jessica R. Allegretti, Brigham and Women’s Hospital, presented the most recent data on the QUASAR study.

The Study

The ongoing QUASAR Phase 3 Induction Study is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating the efficacy and safety of guselkumab as an induction therapy in patients with moderately to severely active ulcerative colitis who had an inadequate response or intolerance to convention therapies like thiopurines or corticosteroids and/or advanced therapies like tumor necrosis factor alpha antagonists, vedolizumab, or tofacitinib.

Guselkumab is an interleukin-23 p19 subunit antagonist.

The study included patients with a baseline modified Mayo score of 5-9, inclusive, rectal bleeding subscore of at least 1, and an endoscopy subscore of at least 2. Patients were evaluated during central review of video endoscopy.

Patients were randomized to receive either intravenous guselkumab 200 mg or placebo at weeks 0, 4, and 8.

Endpoints

The investigators sought a primary endpoint of clinical remission at week 12 and also assessed symptomatic remission, clinical response, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, and safety.

The study included 701 patients who were randomized with a mean age of 40.5 years. The mean duration of ulcerative colitis was 7.5 years, while the mean modified Mayo score was 6.9, Mayo endoscopy subscore of 3 indicating severe disease was 67.9%, median fecal calprotectin was 1641.0 mg/kg, median C-reactive protein was 4.2mg/L, and baseline oral corticosteroid use was 43.1.

The baseline demographic and disease characteristics were balanced across the 2 groups, while almost 50% of patients had a prior failure to advanced therapies for ulcerative colitis. In addition, 47.4% of patients failed 2 or more advanced therapy classes.

The results show a significantly greater proportion of the guselkumab group achieved clinical remission at week 12 compared to placebo (22.6% vs 7.9%; adjusted Δ=14.9%; P <0.001).

Guselkumab induction treatment resulted in significantly greater proportions of patients achieving symptomatic remission, clinical response, endoscopy improvement, and histo-endoscopic mucosal improvement at week 12 and symptomatic remission at week 4 compared to placebo.

Safety

The safety analysis showed the frequencies of treatment-emergent adverse events in the guselkumab group were generally similarity to placebo, with numerically fewer serious adverse events 2.9% vs 7.1%) and AEs leading to discontinuation (1.7% vs 3.9%) in the guselkumab group compared to placebo. There were no adverse events within 1 hour of infusion that were considered serious or resulted in treatment discontinuation.

There were no adverse events within 1 hour of infusion considered serious or resulted in treatment discontinuation.

“In this Phase 3 study, guselkumab 200mg IV induction was safe and effective in the treatment of patients with moderately to severely active ulcerative colitis compared to placebo with clinically meaningful improvements demonstrated across symptomatic and histo-endoscopic outcome measures,” the authors wrote. “Overall, safety results through week 12 were consistent with the known and favorable safety profile of guselkumab in approved indications.”