The QUASAR Phase 3 Induction Study (NCT04033445) investigated the efficacy and safety of the IL-23 p19 subunit antagonist guselkumab in the treatment of moderately to severely active ulcerative colitis. We caught up with Dr Jessica Allegretti (Brigham and Women’s Hospital, Boston, MA, USA), to discuss the aims, design and inclusion criteria of the QUASAR Phase 3 Induction Study, how well clinical endpoints were achieved, the safety profile of guselkumab, and the next steps for guselkumab in ulcerative colitis.
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The abstract ‘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’ was presented at Digestive Disease Week 2023, May 6-9, 2023.
Questions
- What were the aims, design and inclusion criteria of the QUASAR phase 3 induction study? (0:14)
- What clinical endpoints were assessed and how well were these achieved? (1:21)
- What was the safety profile of guselkumab and was this consistent with previous studies? (2:58)
- Following on from these findings, what will be the next steps for guselkumab in ulcerative colitis? (3:41)
Disclosures: Jessica Allegretti discloses consultancy for Janssen, Pfizer, Abbvie, Iterative Scopes, Finch Therapeutics, Seres Therapeutics, Ferring, Merck, Bristol Myer Squibb, Roivant and Adiso, grant/research support from Merck, Janssen and Pfizer, and Speaker’s Bureau participant with BMS, Abbvie and Janssen.
Support: Interview and filming supported by Touch Medical Media Ltd. Interview conducted by Atiya Henry.
Filmed in coverage of DDW 2023.
Transcript
Hi, everyone. My name is Jessica Allegretti. I’m the director of the Crohn’s and Colitis Center at the Brigham and Women’s Hospital in Boston, Massachusetts.
What were the aims, design and inclusion criteria of the QUASAR phase 3 induction study? (0:14)
The QUASAR phase 3 induction study was a randomized double blind placebo controlled study to evaluate the efficacy and safety of guselkumab as an induction therapy in patients with moderate to severely active ulcerative colitis (UC), who had had an inadequate response or loss of response or intolerance to conventional therapies, which are described as corticosteroids or immunomodulators and or advanced therapies such as tumor necrosis factor, alpha antagonists, integran receptor antagonists, or JAK inhibitors. And ultimately, those who were included were adults, so 18 years or older, those 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 score greater than or equal to two. So this is both clinical as well as endoscopic disease activity. And I think it’s important to note that conventional immunosuppressants like corticosteroids up to twenty milligrams a day were permitted upon entry into this study.
What clinical endpoints were assessed and how well were these achieved? (1:21)
So the primary endpoint was clinical remission, which in this study was defined as a Mayo stool frequency sub score of zero or one and not increased from baseline, a Mayo rectal bleeding sub score of zero and a Mayo endoscopic sub score of zero or one with no friability. So, a pretty stringent endpoint. And in this study, 22.6% of the patients who received guselkumab achieved that endpoint compared to 7.9% of those who received placebo, and that was statistically significant. Notably, we also assessed clinical response, which was defined as a decrease from baseline in the modified Mayo score by 30% or more and greater than or equal to two points with either a greater than or equal to one point decrease from baseline in the rectal bleeding subscore, or a rectal bleeding subscore of zero or one. So a less stringent endpoint, but notably 61.5% percent of the patients who received guselkumab achieved clinical response compared to 27.9% of those who received placebo. And again, that was also statistically significant. There are also some other important secondary endpoints of note including endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization. And all of the patients who received guselkumab achieved there was a higher percentage of those who achieved those secondary endpoints compared to placebo, and those were all statistically significant.
What was the safety profile of guselkumab and was this consistent with previous studies? (2:58)
So the safety profile in this study looks great. There were no major safety signals that were identified. There were similar percentages of adverse events overall between both the treatment and the placebo arm. Notably, the incidence of anti drug antibodies through week 12 was very low at 1.5% and none of the ADA positive patients had neutralizing antibodies. And so the overall safety profile that was assessed in this study was very consistent with the known and favorable safety profile of guselkumab for other approved indications.
Following on from these findings, what will be the next steps for guselkumab in ulcerative colitis? (3:41)
So this was just the induction study. So, of course, the next step will be the maintenance study where we’ll see longer term outcomes, so additional efficacy and additional safety data with longer term use, because this study only went through week 12.
Subtitles and transcript are autogenerated
