Induction and maintenance therapy with vedolizumab, a novel biologic therapy for ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by inflammation of the mucosal layer of the colon. The resulting disease includes episodes of recurrent rectal bleeding, increased stool frequency and urgency, abdominal cramps and pain, and systemic symptoms (such as fever, anemia, and weight loss).1 Historical studies have estimated that approximately half of the IBD cases in the United States were attributed to UC; a recent study estimated that UC affected approximately 593,000 persons, with an incidence rate of 8 to 12 per 100,000 persons per year.2,3 The introduction of tumor necrosis factor (TNF) antagonist agents dramatically changed the treatment landscape for UC. As of late 2013, 3 anti-TNF agents have been approved in this setting—infliximab (Remicade, Janssen), adalimumab (Humira, AbbVie), and golimumab (Simponi, Janssen)—with slightly different indications specific for each. Each of these agents has demonstrated benefit for the induction and maintenance of remission in moderate or severe UC. In addition, these biologic agents are noted for their ability to change the natural course of the disease by inducing mucosal healing, reducing glucocorticoid dependence, and decreasing the need for colectomy. Despite their clear impact on the course of therapy, anti-TNF therapy remains inadequate in a significant portion of patients with UC. Approximately 40% of patients with UC fail to respond to infliximab, and another 30% or 40% of patients with UC begin to lose response to infliximab over time.4-6 Thus, alternative therapies have been investigated for UC. One class of agents targets the integrins, cell surface adhesion molecules involved in lymphocyte migration.5,7 Because leukocyte invasion of the intestinal mucosa has been shown to have a role in the pathogenesis of IBD,8 integrin antagonists have been explored for their efficacy in UC. One of the first agents in this class to be evaluated was natalizumab (Tysabri, Biogen Idec) in Crohn’s disease. However, due to its association with progressive multifocal leukoencephalopathy (PML), use of natalizumab has been severely limited in this population. The link between natalizumab and PML has been attributed to its inhibition of both the gut-specific α4β7 integrin and the central nervous system–specific α4β1 integrin.5 Vedolizumab is a novel integrin antagonist that, due to its mechanism of action, only targets the gut-specific α4β7 integrin for inhibition.9,10 Here, Feagan and colleagues report on a phase 3 study that investigated the efficacy and safety of vedolizumab in patients with previously treated moderate to severe active UC.11