P499 Efficacy and safety of 2 or 3 vedolizumab intravenous infusions as induction therapy for ulcerative colitis and Crohn’s disease: results from VISIBLE 1 and 2

Abstract

Background: Vedolizumab is a gut-selective, humanized, alpha4beta7 integrin monoclonal antibody approved for intravenous administration to patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD). A subcutaneous formulation is in development as maintenance therapy. Here, we evaluate clinical response to 2 or 3 doses of vedolizumab intravenous induction therapy in the phase 3 VISIBLE 1 (UC) and VISIBLE 2 (CD) vedolizumab subcutaneous maintenance trials. Method(s): In both trials, patients received open-label vedolizumab 300 mg intravenous induction therapy at Weeks 0 and 2. At Week 6, clinical responders were randomized into the subcutaneous maintenance phase and nonresponders were given a third intravenous infusion and reassessed at Week 14. Clinical response in UC was assessed at Week 6 as a >=3-point and >=30% decrease in complete Mayo score from Week 0 (Baseline) and at Week 14 as a >=2-point and >=25% decrease in partial Mayo score from Week 0, together with a rectal bleeding subscore decrease >=1 point or absolute subscore 70-point decrease in CD Activity Index score from Week 0. Safety of vedolizumab intravenous induction was assessed. The VISIBLE 1 trial has been completed, whereas VISIBLE 2 is currently ongoing (efficacy data only available as captured by an interactive voice response system). Result(s): Among the 383 (UC) and 644 (CD) patients who received open-label vedolizumab induction, 56.1% (106/225) with UC and 63.7% (410/644) with CD had a clinical response at Week 6 after 2 vedolizumab intravenous infusions. Among patients who received a third induction infusion, clinical response rates were 79.7% (114/143) in UC and 63.2% (122/193) in CD. Overall, 86.2% (330/383) of UC patients and 82.6% (532/644) of CD patients achieved a clinical response after 2 or 3 vedolizumab intravenous infusions. In VISIBLE 1, treatment-emergent adverse events (62.9% of patients; 17% treatment-related) and serious treatment-emergent adverse events (10.4% of patients; 0.5% treatment-related) were consistent with prior studies and there were no deaths. Adverse events (30.0%) and lack of efficacy (30.0%) were the main reasons for discontinuation. Conclusion(s): Vedolizumab intravenously induced a clinical response after 2 infusions in more than half of both UC and CD patients. Patients failing to respond after 2 infusions appeared to benefit from a third infusion and responses were achieved in the vast majority of patients overall. The safety/tolerability profile of vedolizumab intravenous induction was consistent with previous reports.Copyright © 2019 AGA Institute. All rights reserved.