Vedolizumab is a humanised IgG1 monoclonal antibody that binds to α4β7 integrin, which is preferentially expressed on certain lymphocytes in the gut. The binding prevents adhesion of these lymphocytes to mucosal endothelial cells, reducing the gastrointestinal inflammation characteristically seen in Crohn's disease and ulcerative colitis.1
The safety and efficacy of vedolizumab as induction and maintenance therapy for ulcerative colitis were evaluated in two integrated randomised controlled trials involving 895 patients with active disease (Mayo Clinic score 6-12, sigmoidoscopy subscore ≥2 and disease extending ≥15cm from the anal verge).2
Induction therapy in ulcerative colitis
Patients in the induction trial were randomised to receive intravenous vedolizumab (300mg, n=225) or placebo (n=149) (cohort 1) at week 0 and 2. An additional 521 patients received open-label vedolizumab (cohort 2).2
The primary endpoint for induction therapy was clinical response, defined as a reduction in the Mayo Clinic score of ≥3 and a decrease of ≥30% from the baseline score, plus a decrease of ≥1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1.2
At week 6, a significantly greater proportion of patients in the vedolizumab group achieved a clinical response than in the placebo group (47.1% versus 25.5%, p <0.001). Similar results were observed in cohort 2, with 44.3% of patients achieving a clinical response.2
Maintenance therapy in ulcerative colitis
Patients from either cohort with a response to vedolizumab at week 6 were included in the maintenance trial and randomised to receive vedolizumab every 8 weeks (n=122) or every 4 weeks (n=125), or placebo (n=126).2
At week 52, patients assigned to continued vedolizumab therapy were more likely to have clinical remission (Mayo Clinic score ≤2 and no subscore >1) than those switched to placebo (41.8% and 44.8% for vedolizumab every 8 weeks or 4 weeks, respectively, versus 15.9% for placebo [p<0.001 for both]).2
Efficacy in Crohn’s disease
Efficacy and safety of vedolizumab were also evaluated in a parallel-group, randomised controlled trial involving 1,115 patients with Crohn’s disease for at least three months and a score of 220 to 450 on the Crohn’s Disease Activity Index (CDAI).3
Patients in the induction study were randomised to receive vedolizumab (300mg, n=220) or placebo (n=148) at weeks 0 and 2 (cohort 1). A further 747 patients received open-label vedolizumab (cohort 2).3
At week 6, the proportion of patients achieving clinical remission (CDAI score ≤150) was significantly greater in the vedolizumab group than in the placebo group (14.5% versus 6.8%, p=0.02). However, rates of CDAI-100 response (≥100-point decrease) did not differ significantly between the two groups (31.4% for vedolizumab versus 25.7% for placebo, p=0.23). In cohort 2, 17.7% of patients achieved clinical remission and 34.4% had a CDAI-100 response.3
Maintenance therapy in Crohn’s disease
Patients from either cohort with a clinical response to vedolizumab (≥70-point decrease in CDAI score) at week 6 were included in the maintenance trial (n=461).3
At week 52, 39% of patients in the vedolizumab 8-weekly dosing group and 36.4% of those in the 4-weekly dosing group were in clinical remission compared with 21.6% of those in the placebo group (p<0.001 and p=0.004, respectively).3
The frequency of adverse effects observed in the ulcerative colitis trial was similar in the treatment and placebo groups.2 In the Crohn’s disease study adverse events were more common in the vedolizumab group, with a greater incidence of nasopharyngitis, infections and serious infections than in the placebo group.3
- Entyvio Summary of Product Characteristics, May 2014.
- Feagan BG et al. N Engl J Med 2013;369:699-710.
- Sandborn WJ et al. N Engl J Med 2013;369:711-21.
Further information: Takeda