Jessica Allegretti, MD, on the QUASAR Study in Ulcerative Colitis

Dr Allegretti reviews the results of the phase 3 QUASAR trial of the interleukin-23 inhibitor guselkumab in ulcerative colitis.

Jessica Allegretti, MD, is an associate professor at Harvard Medical School and medical director of the Crohn's & Colitis Center and director of the fecal microbiota transplant program at Brigham and Women's Hospital in Boston, Massachusetts.

TRANSCRIPT:

Hi everyone. My name is Jessica Allegretti and I'm the medical director of the Crohn's and Colitis Center at Brigham and Women's Hospital in Boston. And I am pleased to share the data that we presented at DDW just last week in Chicago on the efficacy and safety of guselkumab induction therapy in patients with moderately to severely active ulcerative colitis. These are results from the phase 3 QUASAR induction study.

Now for some background, interleukin-23 is a proinflammatory cytokine that plays an important role in the pathogenesis of UC. Guselkumab is a human selective interleukin-23 P19 subunit antagonist that has been approved for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. This study, the phase 3 QUASAR induction study is a randomized double-blind, placebo-controlled study to evaluate the efficacy and safety of guselkumab as induction therapy in patients with moderate to severe UC.

In this study, we enrolled patients who were 18 years or older, again with moderate to severe UC, which was defined as a modified Mayo score of five to nine, and that was inclusive of a Mayo endoscopic sub-score of two or greater. And patients were allowed to be unconventional immunosuppressants going into the study, including corticosteroids up to 20 milligrams. Patients were randomized in a 3-to-2 fashion to receive guselkumab 200 milligrams, IV or placebo, and this was dosed every 4 weeks. And then patients were reassessed at week 12.

Overall, 701 patients were treated, about 421 in the guselkumab arm and 280 in the placebo. Overall rates of treatment discontinuation in this study was about 6%, and the most common reason for discontinuation was either patient withdrawal or worsening of the underlying ulcerative colitis.

We see that the baseline demographics between these 2 groups were overall very similar. Notably, about half of the patients in this study had had prior intolerance or inadequate response to advanced therapies. And of those, about half of them had been exposed to 2 or more advanced therapy classes. With regards to the results, the primary endpoint was clinical remission, and we see that 22.6% of those treated with guselkumab achieved clinical remission compared to 7.9 in the placebo arm, and this was statistically significant.

Secondary outcomes included clinical response, in which we see 61.5% of those in the guselkumab arm achieved clinical response compared to 27.9% in the placebo arm, and this was again, statistically significant. Notable other secondary endpoints included endoscopic improvement, histoendoscopic mucosal improvement, and endoscopic normalization, and all of those achieved statistical significance with those achieving higher rates in the treatment arm compared to placebo.

We also see that patients felt better fairly quickly, so we see that a significantly higher proportion of those treated with guselkumab achieved symptomatic remission as early as week 4 and symptomatic response as early as week 2. Overall, we see an excellent safety profile in this induction study with similar proportion of adverse events in the treatment arm compared to the placebo arm.

The incidence of antidrug antibodies through week 12 was very low, 1.5%, and none of the ADA-positive patients had neutralizing antibodies. So in conclusion, in this phase 3 study, guselkumab 200 milligram IV induction was safe and effective in the treatment of patients with moderate to severely active UC compared to placebo with clinically meaningful improvements demonstrated across symptomatic and histoendoscopic outcome measures. Overall, the safety results through week 12 were consistent with the known and favorable safety profile of guselkumab in other approved indications. Thank you so much for your attention.