CHARLOTTE, NC — People with moderate-to-severe ulcerative colitis benefit from stronger treatment from the start — a combination of monoclonal antibodies — compared with induction with either agent alone, a new phase 2a study demonstrates.
Researchers compared the combination therapy of guselkumab and golimumab (both from Janssen) for 12 weeks, followed by guselkumab monotherapy up to week 38, versus either agent as monotherapy for the full 38 weeks.
Guselkumab is an interleukin-23p19 subunit antagonist being studied to treat inflammatory bowel disease (IBD). Golimumab is a TNF-alpha antagonist being evaluated for ulcerative colitis.
The combination induction strategy “achieved higher rates of clinical remission, endoscopic improvement, composite endpoint of histologic remission, and endoscopic improvement,” said Brian G. Feagan, MD, senior scientific director at the contract research organization Alimentiv Inc and a gastroenterologist at Western University in London, Ontario, Canada.
The findings were presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, North Carolina, being held in person and virtually.
The current research builds on previous week 12 VEGA study results. The earlier findings indicated that blocking interleukin-23p19 by guselkumab and TNF-alpha with golimumab was superior on multiple measures compared with monotherapy.
The new findings are from a randomized, double-blind, proof-of-concept study that included 214 adults with moderately to severely active ulcerative colitis. Participants were naïve to TNF-alpha antagonists and refractory or intolerant to conventional therapy.
Of the participants, 71 were randomly assigned to receive guselkumab, 200 mg intravenous (IV) at baseline and at weeks 4 and 8, plus 100 mg subcutaneous (SC) every 8 weeks.
Another 72 participants received golimumab, 200 mg SC at baseline, and 100 mg SC at weeks 2, 6, and 10, and every 4 weeks thereafter.
The combination group of 71 participants received guselkumab 200 mg IV and golimumab 200 mg SC at baseline, followed by golimumab 100 mg SC at weeks 2, 6, and 10, and guselkumab 200 mg IV at weeks 4 and 8. At week 12, this group switched to monotherapy with guselkumab, 100 mg SC every 8 weeks.
Overall, 13% of patients discontinued treatment prior to week 34, the time of final dose of study intervention.
Feagan noted that they did not see differences between any adverse event, serious adverse event, or adverse event leading to discontinuation among the treatment groups.
Key Findings Through Week 38
The rate of clinical remission in the combination group was 44%. The rate was lower with guselkumab monotherapy at 31% and golimumab monotherapy at 22% at week 38. These percentages were based on a full Mayo Score of 2 or less and no individual subscore greater than 1.
At the same time, the rates of clinical remission by modified Mayo score also favored the combination group at 48%, followed by 31% in the guselkumab group and 21% in the golimumab cohort.
Endoscopic improvement, endoscopic normalization, histologic remission, and composite histologic-endoscopic endpoints were also greater in the combination group than in the monotherapy groups.
“Quite striking differences were maintained up to week 38,” Feagan said. “This combination treatment warrants further investigation, and Phase 3 trials are underway.”
He added that while they were concerned about serious infection, they did not see any differences, with only two serious infections in each of the three groups.
Opportunistic infections were reported for two patients in the combination group: extrapulmonary tuberculosis and cytomegalovirus colitis. No opportunistic infections occurred in the monotherapy groups.
“The early study results, such as the VEGA study, appear promising for combination biologics with a good safety profile,” Jean-Paul Achkar, MD, staff physician in the Center for Inflammatory Bowel Disease at Cleveland Clinic in Ohio and the Kenneth Rainin Endowed Chair for IBD Research, told Medscape Medical News, when asked to comment.
“These data are particularly valuable as we have seemingly reached a therapeutic response ceiling for single biologic therapy, and we need to determine the added benefit and safety profile of a combination of two biologics or the combination of a biologic and a small molecule,” added Achkar, who served as the session comoderator.
A meeting attendee asked about the likelihood of regulatory approval for this combination based on evidence like this study.
“I think they have to,” Feagan said. “We’ve probably seen our best results yet in Crohn’s disease, and we’re still at 50% [response rate for monotherapy]. If we’re ever going to come to terms with IBD, I don’t think it’s monotherapy.”
Feagan added that with combination therapy, “physicians will often worry about economics, but I think that’s a surrogate for their concerns about infection.”
However, he noted that “the better the agents we have, the better the incremental cost effectiveness. So, I don’t think economics is the issue; the issue is safety.”
Another meeting attendee asked if the results might apply to other biologic combinations.
“This model was picked to show the additive effect of the anti-p19 and the TNF antagonist,” Feagan said.
Similar results could be expected with a combination of treatments from the same classes, he said, but the treatment potential of other drug-class combination is unclear.
American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting: ACG Newsworthy Abstract 40. Presented October 25, 2022.
The study was funded by Janssen Research and Development. Feagan reports being a consultant for Janssen. Achkar reports no relevant financial relationships.
Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.
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