FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
When treating patients for ulcerative colitis (UC), clinicians should consider using vedolizumab, because the drug has been found to be both safe and highly effective in patients who have never received tumor necrosis factor (TNF)–antagonist treatment and those who have but did not benefit from it, according to a study published in the February issue of Clinical Gastroenterology and Hepatology ( doi: 10.1016/j.cgh.2016.08.044 ).
“Approximately 50% of patients with UC do not respond to induction therapy with TNF antagonists or lose response over time such that after 1 year of treatment, clinical remission is observed in only 17%-34% of patients,” explained the authors of the report, led by Brian G. Feagan, MD , of the University of Western Ontario in London. “Furthermore, the risk of serious infection (with immunosuppressants in general, and TNF antagonists specifically) is an important concern [so] alternative approaches to treatment are needed.”
For this study, Dr. Feagan and his colleagues turned to the GEMINI 1 trial , which evaluated vedolizumab in patients with moderate and severe UC via a multicenter, phase III, randomized, placebo-controlled trial. This study produced data on 374 subjects who had been randomized into cohorts receiving either vedolizumab intravenously or a placebo. However, this number was deemed too low, so a further 521 patients were enrolled for an open-label study and randomized in the same 3:2 ratio as the previous study. The former study was called Cohort 1 and the latter called Cohort 2.
“Eligible patients had UC for [at least] 6 months before enrollment, MCS [Mayo Clinic scores for disease activity] from 6 to 12, and endoscopic subscores of [at least] 2 within 7 days before the first dose of study drug, and evidence of disease extending [at least] 15 cm proximal to the rectum,” the authors explained.
Vedolizumab was administered at baseline, with follow-up evaluations at 2, 4, and 6 weeks. Subjects who experienced a clinical response – defined as an MCS reduction of at least 3 points and 30%, along with at least a 1-point reduction in rectal bleeding and an absolute rectal bleeding subscore of either 0 or 1 – were re-randomized into cohorts that received the drug every 4 weeks or every 8 weeks, for a period of up to 46 weeks. The total length of the study was, therefore, 52 weeks; for patients that were re-randomized, follow-up evaluations took place every 4 weeks.
A total of 464 patients who were enrolled and completed the study were naive to TNF antagonists, while 367 had previously been treated with TNF antagonists unsuccessfully. At 6-week follow-up, 53.1% of naive subjects receiving vedolizumab had achieved clinical response, versus 26.3% of naive subjects on placebo (absolute difference, 26.4%; 95% confidence interval, 12.4-40.4). Similarly, those with previous TNF antagonist exposure who were given vedolizumab had a 39.0% clinical response rate, versus 20.6% of those on placebo (AD, 18.1%; 95% CI, 2.8-33.5).
At week 52, naive subjects on vedolizumab continued to have far higher rates of clinical response than did those on placebo, with 46.9% and 19.0%, respectively (AD, 28.0%; 95% CI, 14.9-41.1). For those with previous TNF antagonist exposure, the disparity between vedolizumab and placebo was similarly profound: 36.1% versus 5.3%, respectively (AD, 29.5%; 95% CI, 12.8-46.1).
Adverse event rates between naive and previously exposed patients were not significantly different, according to the findings. In naive patients, 74% of those on vedolizumab experienced an adverse event, and 9% experienced a serious adverse event. For those on placebo, those rates were 75% and 16%, respectively. For patients who had previously been on a TNF antagonist, subjects on vedolizumab had an 88% rate of adverse events and a 17% rate of serious adverse events, compared with 84% and 11%, respectively, for those on placebo.
“It is notable that, in maintenance, the absolute remission rates were substantially lower in the TNF failure population for both vedolizumab-treated and placebo-treated patients,” the investigators noted, positing that “The relatively low placebo response rate in the TNF-failure group could be attributed to the presence of a greater proportion of patients with more refractory disease and poor prognostic factors, such as pancolitis and long disease duration.”
The study was funded by Millennium Pharmaceuticals. Dr. Feagan disclosed serving as a consultant and receiving financial support for research from Millennium and other companies. No other coauthors reported relevant financial disclosures.
