Vedolizumab safe for inflammatory bowel disease

Last Updated: 2016-02-24

By Marilynn Larkin

NEW YORK (Reuters Health) - Vedolizumab safely treats ulcerative colitis and Crohn's disease, researchers report in a study that integrates safety data from six clinical trials.

"This data confirms the good safety profile of vedolizumab, in particular regarding low risk of systemic infections," lead author Dr. Jean-Frederic Colombel told Reuters Health by email. "This is likely due to the mechanism of action of the drug, which is selectively blocking the recruitment of lymphocytes to the gut."

Vedolizumab, an integrin receptor antagonist, is a monoclonal antibody that specifically binds to the alpha4beta7 integrin. It blocks the interaction of the integrin with MAdCAM-1 (mucosal addresin cell adhesion molecule-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue.

"Still, the safety profile of vedolizumab, as for other drugs, needs to be assessed in long-term registries," Dr. Colombel added. "Meanwhile, it is already widely used in patients with ulcerative colitis or Crohn's disease who have been refractory to anti-TNF therapies, or as a first-line biologic agent, especially in patients with a higher risk of infections, such as elderly people."

As reported online February 18 in Gut, Dr. Colombel and colleagues combined safety data from six trials and evaluated adverse events in patients who received at least one dose of vedolizumab or placebo. A total of 2,830 patients had 4,811 patient-years of exposure.

Results revealed no increased risk of any infection or serious infection; infrequent reports (up to 0.6% of patients) of serious clostridial infections, sepsis or tuberculosis; and no cases of progressive multifocal leukoencephalopathy. Infusion-related reactions were reported in up to 5% of patients in each study. Eighteen patients exposed to the drug were diagnosed with a malignancy.

Commenting by email, Dr. Louis Cohen, a researcher and gastroenterology instructor at Mount Sinai Hospital, New York City, told Reuters Health it "provides the most comprehensive review to date of the safety of vedolizumab use in both ulcerative colitis and Crohn's disease," and that the rate of adverse events reported in over 4800 patient years of exposure was "impressively low."

"While the median follow up was one year, this initial report is very promising and suggests that a highlight of this new therapeutic may be a high degree of tolerability in IBD patient cohorts," he said. "Most importantly, there were no reports of progressive multifocal leukoencephalopathy in patients treated with vedolizumab, which had been a serious adverse event identified in the use of natalizumab, a therapeutic (agent) that also focused on blockade of lymphocyte trafficking, though by less specific integrin targeting."

Dr. Cohen also observed that "while there are no studies to date that provide direct comparisons between vedolizumab and other currently used therapeutics, the authors provide some insight into complications commonly seen with other therapies and suggest that vedolizumab may provide a safe alternative."

"Longer term studies in more patients will be critical to fully understanding the risk of vedolizumab, especially for complications such as malignancy and intestine-specific infections, as noted by the authors," he continued. "We look forward to seeing how the safety profile of vedolizumab evolves over time as we also better understand the efficacy of this new therapeutic in populations of patients with IBD."

Takeda Pharmaceuticals provided funding for the study and four of the coauthors are employees of the company. Dr. Colombel is a consultant to Takeda and other pharmaceutical companies. Commentator Dr. Cohen has no connection to Takeda.

SOURCE: http://bit.ly/1QFsKLx

Gut 2016.