Phase III VARSITY trial shows Entyvio superior to Humira in ulcerative colitis

Takeda Pharmaceutical announced results from the Phase IIIb head-to-head VARSITY study which demonstrated that the gut-selective biologic Entyvio (vedolizumab) was superior to the anti-tumor necrosis factor-alpha (anti-TNFalpha) biologic Humira (adalimumab) in achieving clinical remission in patients with moderately to severely active ulcerative colitis at week 52. Data showed that 31.3% (n=120/383) of patients receiving vedolizumab intravenous (IV) achieved the primary endpoint of clinical remission compared to 22.5% (n=87/386) of patients treated with adalimumab subcutaneous (SC) at week 52, with the difference being statistically significant.

Furthermore, treatment with vedolizumab was associated with significantly higher rates of mucosal healing at week 52, with 39.7% of patients receiving vedolizumab achieving mucosal healing compared to 27.7% treated with adalimumab. A non-statistically significant difference in favor of adalimumab was seen in the percentage of patients using oral corticosteroids at baseline who discontinued corticosteroids and were in clinical remission at week 52. While the study was not powered to compare the safety of the two biologics, patients treated with vedolizumab (62.7%) had a lower rate of overall adverse events over 52 weeks than patients treated with adalimumab (69.2%), with a lower rate of infections reported in patients treated with vedolizumab (33.5%) as compared to adalimumab (43.5%). The rate of serious adverse events was also lower in vedolizumab-treated patients than adalimumab (11.0% vs. 13.7% respectively). These results were announced at the 14th Congress of the European Crohn’s and Colitis Organisation.

Comment: Vedolizumab is a gut-selective biologic and is approved as an intravenous (IV) formulation. It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1). MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.

A number of inflammatory bowel disease learning zones are available to view for more information and resources: Disease, Inflammatory Bowel Disease Assessment Tools, Anti-integrins in Inflammatory Bowel Disease.