P510 Dose escalation of subcutaneous vedolizumab in patients with ulcerative colitis: A post hoc analysis of the VISIBLE trial data

Abstract

Vedolizumab (VDZ), a gut-selective, α 4β7 integrin monoclonal antibody, is approved for intravenous (IV) administration to patients with moderate-severe ulcerative colitis (UC). Subcutaneous (SC) VDZ was evaluated for maintenance therapy for UC in VISIBLE 1, a double-blind, placebo-controlled, Phase 3 study, and its open-label extension (OLE). We evaluated the efficacy of increasing dose frequency of VDZ SC from every-2-weeks (Q2W) to weekly administration (QW) after treatment failure (disease worsening or need for rescue medication).In VISIBLE 1 (NCT02611830; EudraCT 2015-000480-14), a Q2W dosing regimen was used for patients with UC who achieved clinical response at week 6 (after open-label IV VDZ inductions at weeks 0 and 2) and were randomised to maintenance treatment with VDZ SC. Patients who did not respond at week 6 but responded by week 14 rolled over to the VISIBLE OLE (NCT02620046; EudraCT: 2015-000482-31) and received Q2W VDZ SC dosing. In VISIBLE 1 and the OLE, 2 groups of patients experienced dose escalation: (1) patients who entered the VISIBLE OLE study on a Q2W VDZ dosing regimen but experienced disease worsening and were escalated to QW dosing (OLE Q2W/QW); and (2) patients who experienced treatment failure during Q2W VDZ treatment in VISIBLE 1, rolled over to OLE, and were escalated to a QW dosing regimen (VISIBLE 1 treatment failure). Efficacy was evaluated by clinical remission and response rates after dose escalation using partial Mayo scores at the visits in the Visible OLE study. In this interim analysis, not all patients continuing in the trial had not completed all study visits. Only patients who had completed a given visit (evaluable patients) were included in the analyses for that visit.Of the 54 patients who received dose escalation 52% were male. Mean age was 39 years, mean UC duration was 7.4 years; 76% had severe disease activity (Mayo 9–12) at baseline, and 43% had prior anti-TNF therapy failure (Table 1). Of the patients with dose escalation, 27.1% (13/48 evaluable patients) recaptured clinical remission 16 weeks after dose escalation and 10.8% (4/37 evaluable patients) were in clinical remission after 48 weeks (Table 2). A similar trend was observed for clinical response rates in this patient population.Increasing the frequency of VDZ SC dosing to QW recaptured lost response to treatment for some patients. These are interim results of the OLE study; further follow-up during the ongoing OLE will provide more insight into the long-term efficacy and safety of dose escalation with VDZ SC.