Unlike tumor necrosis factor (TNF) inhibitors, which were the first biologics to be licensed for use in IBD, vedolizumab inhibits the migration of leukocytes in the GI tract by preventing the alpha4beta7 subunit from binding to the adhesion molecule MAdCAM-1. It has been unclear whether or to what degree vedolizumab shares the known risk, albeit small, of inducing opportunistic infections observed with TNF inhibitors.
The most recent data continue to suggest that there is no greater risk of infection or other complications of immune function for vedolizumab than other biologics, and the risk may be lower. In the pooled GEMINI data with 1,434 patients followed during induction and maintenance phases with data in some groups out to 104 weeks, the overall percentages of infection and the individual infections rates have been “similar,” Dr. Loftus reported.
“The exception has been nasopharyngitis, which was less common in the placebo group,” said Dr. Loftus, providing relative rates of approximately 13% and 9% for vedolizumab and placebo, respectively. He noted, however, that the length of follow-up has been longer in the vedolizumab relative to the placebo groups. Rates of tuberculosis, Clostridium difficile colitis, and other serious infections have not differed significantly.
In addition, there has been no association between vedolizumab and progressive multifocal leukoencephalopathy (PML) so far. Concern about a risk for PML was raised by the relationship of vedolizumab to natalizumab, which blocks the same adhesion compounds and has been associated with PML. The absence of PML in follow-up so far is consistent with evidence that the activity of vedolizumab, unlike the activity of natalizumab, is largely or entirely confined to the GI tract.
No multicenter, randomized trials have yet to be conducted comparing either the efficacy or safety of vedolizumab, which was approved in May 2014 for the treatment of moderate to severe Crohn’s disease and ulcerative colitis, to other biologics used in IBD.