Efficacy of Vedolizumab in Fistulising Crohn's Disease: Exploratory Analyses of Data from GEMINI 2

Abstract

Background and aims: Medical management of fistulising Crohn's disease [CD] is constrained by the limited number of available therapies. We evaluated the efficacy of vedolizumab, a gut-selective α4β7 integrin antagonist approved for treating moderately to severely active CD, in a subpopulation of patients with fistulising CD who participated in the GEMINI 2 trial [NCT00783692].

Methods: Exploratory analyses of data from the GEMINI 2 trial were conducted in 461 responders to 6-week vedolizumab induction therapy who received maintenance placebo [VDZ/PBO, N = 153] or vedolizumab [VDZ/VDZ, N = 308]. Fistula closure rates were assessed at Weeks 14 and 52, and the time to fistula closure was analysed by the Cox proportional hazards model with adjustments for significant covariates.

Results: At entry into the maintenance period, 153 [33%] patients had a history of fistulising disease and 57 [12%] patients had ≥1 active draining fistula. By Week 14, 28% of VDZ/VDZ-treated patients compared with 11% of VDZ/PBO-treated patients (95% confidence interval [CI], -11.4 to 43.9) achieved fistula closure. Corresponding rates at Week 52 were 31% and 11% (absolute risk reduction [ARR]: 19.7%; 95% CI, -8.9 to 46.2). Similarly, VDZ/VDZ-treated patients had faster time to fistula closure and were more likely to have fistula closure at Week 52 [33% vs 11%; HR: 2.54; 95% CI, 0.54-11.96]. Prior failure of antibiotic therapy was a negative predictor of fistula closure [HR: 0.217; 95% CI, 0.059-0.795; p = 0.021], whereas trough vedolizumab concentrations did not affect closure rates.

Conclusions: Our findings are consistent with the beneficial effect of vedolizumab treatment for fistulising CD.

Figure 1.

Fistula closure in patients with ≥1 draining fistula at baseline, Week 14 and Week 52 by treatment group. All patients in this analysis [n = 57] received induction treatment with vedolizumab [Weeks 0–6, not shown]. Black bars represent the VDZ/PBO maintenance group [n = 18] and grey bars represent the VDZ/VDZ maintenance group [n = 39]. ^aMaintenance baseline, Week 6. Abbreviations: PBO, placebo; VDZ, vedolizumab.

Figure 2.

[A] Time to fistula closure in all patients with fistula at baseline and [B] the subgroup of patients with perianal fistula only by treatment group. All patients in this analysis had ≥1 draining fistula at baseline [n = 57] and received previous induction treatment with vedolizumab [Weeks 0–6]. Kaplan–Meier 12-month estimate of fistula closure with VDZ/VDZ treatment is shown. Abbreviations: CI, confidence interval; HR, hazard ratio; PBO, placebo; VDZ, vedolizumab.