Guselkumab safe, effective as induction therapy for UC

Induction therapy with guselkumab, an interleukin-23 p19 subunit antagonist, results in clinical and symptomatic remission, as well as other endoscopic improvements in patients with moderate-to-severe active ulcerative colitis (UC), according to the QUASAR study presented at DDW 2023.

“Many people living with UC, especially those who have had inadequate response to other treatments, live with uncertainty and continue to experience debilitating symptoms,” said lead author Dr Jessica Allegretti from the Crohn's and Colitis Center at Brigham and Women's Hospital in Boston, Massachusetts, US.

During the phase III induction study, 701 patients with moderate-to-severe UC (mean age 40.5 years, 43.1 percent female, mean UC duration of 7.5 years), who had an inadequate response or intolerance to conventional and/or advanced therapies, were randomized 3:2 to receive either IV guselkumab 200 mg (n=421) or placebo (n=280) at weeks 0, 4, and 8, and observed through week 12. [DDW 2023, abstract 913b]

At week 12, significantly more guselkumab-treated patients achieved the primary endpoint of clinical remission* than the placebo-treated patients (22.6 percent vs 7.9 percent; p<0.001).

A significantly higher percentage of patients treated with guselkumab vs placebo also achieved symptomatic remission** (49.9 percent vs 20.7 percent; p<0.001) and clinical response*** (61.5 percent vs 27.9 percent; p<0.001) at week 12.

In addition to these key secondary endpoints, guselkumab recipients also had significant endoscopic improvement (26.8 percent vs 11.1 percent; p<0.001), histo-endoscopic mucosal improvement (23.5 percent vs 7.5 percent; p<0.001), and endoscopic normalization (15.0 percent vs 5.0 percent; p<0.001) at week 12 compared with the placebo recipients.

Similar rates of treatment-emergent adverse events (TEAEs) were observed between the guselkumab and placebo arms (49.4 percent vs 49.3 percent), with fewer serious AEs (2.9 percent vs 7.1 percent) and AEs leading to treatment discontinuation (1.7 percent vs 3.9 percent) reported with guselkumab.

“Of note, no AEs within 1 hour of infusion were considered serious or resulted in treatment discontinuation,” Allegretti noted.

“Safety results through week 12 were consistent with the known and favourable safety profile of guselkumab in approved indications,” she added.

“Overall, guselkumab 200 mg IV induction was safe and effective in the treatment of patients with moderately to severely active UC compared with placebo, with clinically meaningful improvements demonstrated across symptomatic and histo-endoscopic outcome measures,” said Allegretti.

“This phase III data represents an important step in the advancement of a new treatment for moderately to severely active UC, as researchers continue to investigate therapeutic options that have the potential to provide relief for individuals at all stages of the disease,” she noted.