CHARLOTTE, N.C. – , a 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.
University of Western Ontario, London
Dr. Brian G. Feagan
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 and a gastroenterologist at Western University in London, Ont.
The findings were presented at the annual meeting of the American College of Gastroenterology.
Study design
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 naive 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.
Dr. 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,” Dr. 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.