DOP16 An evaluation of the exposure–efficacy relationship for subcutaneous vedolizumab maintenance treatment of Crohn’s disease: Pharmacokinetic findings from VISIBLE 2

Abstract

Background: The exposure-efficacy relationship and immunogenicity rates of the new vedolizumab subcutaneous (SC) formulation have been established for maintenance treatment of ulcerative colitis (UC).1 Here, we report vedolizumab SC exposure-efficacy and immunogenicity in Crohn's disease (CD). Method(s): VISIBLE 2 (NCT02611817; EudraCT 2015-000481-58) was a pivotal, Phase III, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of vedolizumab SC (108 mg every 2 weeks) as maintenance treatment in patients with moderately to severely active CD. After intravenous (IV) vedolizumab (300 mg Weeks 0 and 2) induction, patients with a clinical response at Week 6 (>= 70-point decrease in CD Activity Index [CDAI] from Week 0) were randomized to blinded maintenance treatment and included in the analyses. Vedolizumab serum concentrations were measured before dosing using an enzyme-linked immunosorbent assay. Immunogenicity was assessed with a drug-tolerant electrochemiluminescence assay. Predicted vedolizumab trough concentrations at Week 52 were grouped by quartiles (Qs) andWeek 52 efficacy outcome rates calculated for each Q. Missing efficacy outcome data were imputed as failures. Efficacy outcomes were clinical remission (CDAI = 100-point decrease in CDAI from Week 0 at Week 52). Result(s): After vedolizumab IV induction (n = 644), patients with a clinical response were randomized and received vedolizumab SC (n = 275) or placebo (n = 134) as maintenance treatment. At Week 52, patients on vedolizumab SC maintenance treatment had a positive exposure-efficacy relationship for clinical remission (Q1, 37.7%; Q4, 50.7%) and enhanced clinical response (Q1, 37.7%; Q4, 53.6%; Figs 1,2). Overall, 7/275 patients (2.5%) on vedolizumab SC (after vedolizumab IV induction) developed anti-vedolizumab antibodies (AVAs): 3/7 patients were persistently AVA-positive and 4/7 had neutralizing antibodies. Five of seven AVA-positive patients on vedolizumab SC did not achieve clinical remission and enhanced clinical response at Week 52; two of those patients were persistently AVA-positive. Immunogenicity was not associated with injection-site reactions or hypersensitivity reactions. Conclusion(s): These preliminary results suggest a trend for higher vedolizumab SC serum concentrations with greater efficacy in CD, but the association was less pronounced than that reported in UC.1 The AVA rate was similar to what was observed in prior vedolizumab IV studies.2 In this study, vedolizumab immunogenicity appeared to be associated with clinical outcome.