Guselkumab Induction Safe and Effective in Ulcerative Colitis

Guselkumab (Tremfya) results in clinically meaningful improvements demonstrated across symptomatic and histo-endoscopic outcome measures for patients with ulcerative colitis compared with placebo, according to the latest iteration of data from the ongoing QUASAR study presented at the annual Digestive Disease Week conference.

In this exclusive MedPage Today video, lead author Jessica R. Allegretti, MD, MPH, medical director of the Crohn’s and Colitis Center at Brigham and Women’s Hospital in Boston, explained how the data continue to point to guselkumab being a safe and effective treatment.

Following is a transcript of her remarks:

With regards to the background, why did we do this study? So interleukin-23 is a pro-inflammatory cytokine that plays an important role in the pathogenesis of ulcerative colitis. Guselkumab is a human selective interleukin-23 p19 subunit antagonist that has been approved already for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis.

This study, the QUASAR phase III induction study, is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of guselkumab as induction therapy in patients with moderately to severely active ulcerative colitis who had inadequate response, loss of response, or intolerance to either conventional therapies like corticosteroids or immunomodulators and/or advanced therapies such as anti-TNF [tumor necrosis factor] agents, anti-integrin receptor antagonists, or JAK [Janus kinase] inhibitors.

This study, essentially patients were enrolled who are adults, so 18 years or older, again had moderate to severely active UC [ulcerative colitis], which was defined as a modified Mayo score of 5 to 9. And that did include a Mayo endoscopic subscore of 2 or greater. And note again that patients were allowed to be on corticosteroids at least of 20 milligrams or less on entry into the study.

Patients were randomized in a 3-to-2 fashion to receive guselkumab 200 milligrams IV or placebo, and they received that therapy every 4 weeks through the 12-week induction period. And again the last dose was at week 8, and then patients were followed up with a final endoscopy at week 12.

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

The groups overall looked very similar. I would just note that this was a fairly sick patient population. We see between 65% and 70% of patients had a Mayo endoscopic subscore of 3 — so the highest score you can have going into the trial.

About half of the patients in each arm had extensive colitis, and there was a mean fecal calprotectin of about 1600 [mg/kg] in both arms. So again, a fairly sick patient population.

With regards to prior medication use, about half of the patients in each group were exposed to prior advanced therapies, and of those, about half had been exposed to two or more advanced therapy classes.

Now with regards to the primary outcome, which was clinical remission, 22.6% of the patients in the treatment arm achieved clinical remission compared to 7.9% in the placebo arm, with a delta of 14.9%. With regards to clinical response, 61.5% of those in the treatment arm achieved clinical response compared to 27.9 in the placebo arm.

We also looked at several important secondary outcomes including endoscopic improvement, histo-endoscopic mucosal improvement, as well as endoscopic normalization, and all were statistically significant in favor of the treatment compared to placebo.

We don’t see any major safety signals coming out of this induction study. We see fairly similar rates of adverse events in both the placebo and the guselkumab arm with no signals for serious infections or other adverse events of special interest.

So in conclusion, in this phase III study, guselkumab 200 milligrams 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 histo-endoscopic outcome measures.

Overall safety results through week 12 were consistent with the known and favorable safety profile of guselkumab in approved indications.

Thank you so much.