Vedolizumab Induction Therapy for Patients With Crohn’s Disease and Prior Anti-TNF Antagonist Failure: A Randomized, Placebo-controlled, Double-blind, Multicenter Trial

Abstract

Background: The primary analysis of the efficacy and safety of vedolizumab (VDZ) as induction therapy in Crohn's disease (CD) was conducted in patients (pts) with prior anti-tumour necrosis factor (TNF) failure (GEMINI III; NCT01224171). Methods: In a phase 3 study, pts with moderately to severely active CD (CD Activity Index [CDAI] 220-400) and failure or intolerance to prior therapy were randomised 1:1 to receive intravenous VDZ 300 mg or placebo (PBO) at wks 0, 2 and 6. The primary endpoint was clinical remission (CDAI <150) at wk 6 in pts with prior anti-TNF failure. Secondary endpoints included clinical remission at wk 6 in the overall population, clinical remission at wk 10 in anti-TNF failure and overall populations, sustained clinical remission (CDAI <150 at weeks 6 and 10) in both populations, and CDAI 100 response (>100-point decrease from baseline in CDAI) in the anti-TNF failure population. Endpoints were tested sequentially; Hochberg method was used to control alpha. Results: Baseline CDAI was slightly higher in the VDZ than the PBO group (313.9 vs 301.3; P = 0.015); pt characteristics were otherwise similar. In the anti-TNF failure population, clinical remission rates at wk 6 were not statistically significant between VDZ and PBO groups; thus, key secondary endpoint analyses are exploratory. (Table Presented) Greater proportions of VDZ-treated pts had CDAI 100 response at wk 6 and were in clinical remission by wk 10 vs PBO in the anti-TNF failure and in the overall populations. In the overall population, more pts in the VDZ group had sustained clinical remission vs PBO. Treatment-emergent AEs were reported in 56% of VDZ pts vs 60% of PBO pts; serious AEs were reported in 6% vs 8%, respectively, with no deaths. Conclusions: In the anti-TNF failure population, clinical remission rates at wk 6 were not higher with VDZ vs PBO. However, CDAI 100 response at wk 6 and clinical remission at wk 10 were higher in the VDZ group, suggesting that remission may be achieved beyond the 6-wk period of treatment and evaluation used for the primary analysis in this study. VDZ therapy had beneficial effects in the anti-TNF failure and overall populations vs PBO.