A New Drug for Crohn’s Disease

The August 4, 2014 issue of The Medical Letter on Drugs for Inflammatory Bowel Disease includes a brief discussion of vedolizumab (Entyvio), the second integrin receptor antagonist to be marketed in the US for treatment of IBD. Natalizumab (Tysabri), which is also used to treat multiple sclerosis, was the first, but its use has been limited by a devastating side effect, progressive multifocal leukoencephalopathy (PML), which is caused by reactivation of the JC polyomavirus. Natalizumab affects receptors both in the brain and the gut. Vedolizumab appears to act only on the gut, so it is possible that it will not cause PML, and so far it has not.

Both natalizumab and vedolizumab are monoclonal antibodies that reduce inflammation by inhibiting the migration of lymphocytes. The hope was that they could help patients, particularly those with Crohn’s disease, who had not responded to one or more TNF inhibitors. Crohn’s patients who do not respond to one TNF inhibitor may respond to another, but the rate of response is lower the second time around. In the pivotal clinical trial of vedolizumab in Crohn’s (WJ Sandborn et al, N Engl J Med 2013; 369:711), the results were positive, but not spectacular. We did not discuss possible reasons for these modest results in our IBD review, but the authors of the trial did, and we thought it might be helpful to our readers to mention some of the points they made.

One possible explanation, of course, is that vedolizumab is not very effective. But there are some alternative explanations. For one thing, this was a group of patients with severe Crohn’s: 37% had a history of fistulizing disease and 42% had undergone at least one operation for the disease. About 50% had had a treatment failure with one or more TNF inhibitors. All of that previous treatment (about half of the patients with the treatment failures on TNF inhibitors had not responded to initial treatment) could have contributed to modest responses to vedolizumab. And it could be that inhibiting lymphocyte migration in the GI tract takes longer than TNF inhibition to have an effect and may be better suited to maintaining remissions than to inducing them.

We will publish a separate article on vedolizumab in an upcoming issue of The Medical Letter. Hopefully, we can shed some additional light on its potential for treatment of Crohn’s disease and ulcerative colitis as well.

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