Vedolizumab for the treatment of moderately to severely active ulcerative colitis

Abstract

Ulcerative colitis is a chronic, idiopathic, inflammatory bowel disease characterized by a relapsing and remitting course. A substantial proportion of patients fail conventional therapies despite therapy with immunosuppressives and tumor necrosis factor antagonists. Accordingly, newer therapeutic agents that target disease-specific inflammation and minimize adverse events are required. Central to the pathogenesis of ulcerative colitis is an aberrant host response to commensal microorganisms with a resultant dysregulation of gut immune homeostasis and lymphocyte trafficking. Recently, a newer biologic, vedolizumab, which blocks lymphocyte trafficking, has been developed for use in moderate to severe ulcerative colitis. The efficacy of this agent has been demonstrated to be similar to that of other currently available biologics, and the selectivity of this agent in blocking lymphocyte migration to the gut has substantially reduced treatment-related adverse events. The drug has now been approved for use in the United States and Europe, and, although the exact positioning of this biologic in clinical practice is yet to be defined, it represents an important new chapter in our armamentarium of treatment options for this population. In this review, we will highlight key considerations to be made by providers when using this agent in clinical practice.

Keywords: inflammatory bowel disease; mucosal addressin cell adhesion molecule-1; ulcerative colitis; vedolizumab; α4β7.

Figure 1:

Factors considered to play a role in the pathogenesis of ulcerative colitis.

Figure 2:

Rates of response, remission, and mucosal healing in the induction phase of the GEMINI 1 trial. **Statistically significant difference for vedolizumab (Vedo) vs placebo (p≤0.001); p value not reported for open-label Vedo vs placebo.

Figure 3:

Rates of response, remission, and mucosal healing in the maintanence phase of the GEMINI 1 trial. *Statistically significant difference for vedolizumab (Vedo) vs placebo (p≤0.01); **Statistically significant difference for Vedo vs placebo (p≤ 0.001). Durable clinical response was defined as response at both weeks 6 and 52; durable clinical remission was defined as remission at both weeks 6 and 52; steroid-free remission was assessed in patients receiving steroids at baseline.

Figure 4:

Clinical outcomes stratified by reason for tumor necrosis factor antagonist failure. Rates of clinical response, clinical remission, and mucosal healing at week 6 are shown in panel A; durable clinical response, durable clinical remission, and mucosal healing at week 52 are shown in panel B. VDZ = vedolizumab.