By Marilynn Larkin
NEW YORK (Reuters Health) - 3/6/2019
There is "no strong evidence" to suggest that vedolizumab can treat pre-existing extra-intestinal manifestations (EIMs) of inflammatory bowel disease (IBD), although the drug may reduce the occurrence of new ones, a systematic review suggests.
EIMs occur in up to 55% of patients with Crohn's disease and 35% of those with ulcerative colitis. These manifestations can affect the patient's quality of life, represent a substantial cost on the health care system, and should be considered as part of treatment decisions, according to Dr. Peyrin-Boulet of the University of Lorraine and colleagues.
Because no controlled trials have assessed the effectiveness of vedolizumab in EIMs in adults with IBD, the researchers undertook a literature search to summarize existing data.
As reported online May 10 in the Journal of Crohn's and Colitis, three interventional studies (one randomized trial with 1,032 patients; two open-label trials with 347); five non-interventional studies with a total of 1,496 patients; and three case series of 17 patients were included.
Vedolizumab did not show any effectiveness in primary sclerosing cholangitis (PSC), according to the authors. No effect was seen in pre-existing manifestations of arthralgia and arthritis, although the occurrence of new rheumatic symptoms was lower among vedolizumab users compared to placebo. Nonetheless, symptoms were higher than with tumor necrosis factor inhibitors.
Further, vedolizumab did not seem effective against cutaneous manifestations.
Summing up, the authors state, "The use of vedolizumab may not be efficacious in IBD patients with pre-existing EIMs, but it might reduce the occurrence of new EIMs."
Dr. Dana Lukin, Clinical Director of Translational Research at Jill Roberts Center for Inflammatory Bowel Disease and Assistant Professor of Clinical Medicine with New York Presbyterian Hospital and Weill Cornell Medicine in New York City, commented, "While the included studies all reported on EIM, none of these was designed specifically to assess EIM as a primary or secondary outcome. The small number of events reported limits the ability to draw many conclusions from the data."
"The methodology used is sound and the conclusions are valid, albeit limited," he told Reuters Health by email. "Given the differences in study design and outcomes assessed, it is difficult to directly assess the impact of vedolizumab on EIM from this systematic review. Several of the studies are retrospective and/or case studies and no objective indices for grading of EIM severity were used, suggesting that bias may affect the results."
"As vedolizumab's mechanism of action specifically targets the intestine, and several hypotheses for the etiology of EIM involve a systemic inflammatory response possibly mediated by TNF, one would not intuitively expect it to be highly effective against EIM," he noted. "Additionally, many EIMs are not dependent on luminal disease activity, so it is not surprising that a gut-selective biologic would not resolve these conditions."
"Data from prospective studies designed to detect differences in EIM using objective endpoints, such as spondyloarthropathy disease activity indices, may help to more clearly elucidate the impact of biologic therapies on EIM," he continued. "The data from the present study suggest that the presence of active EIM in patients with IBD may be one additional factor to consider when positioning biologic therapies."
Dr. Keith Sultan, assistant professor at The Feinstein Institute for Medical Research in Manhasset, New York, told Reuters Health by email that the study conclusions "match what clinicians have long assumed to be a limitation of vedolizumab - i.e., that (its) focused mechanism - selectively targeting intestinal inflammation - might not provide benefit for IBD-related inflammatory complications outside of the bowel. The results, while limited and open to future study, provide useful guidance to doctors and their patients as they choose among an ever-increasing array of IBD therapies."
Dr. Peyrin-Biroulet declined to provide a comment.
J Crohns Colitis 2019.