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
E. V. LoftusJr1, W. J. Sandborn2, D. Wolf3, S. Danese4, J. Chen5, X. Yao5, K. Kisfalvi*5, S. Vermeire6
1Mayo Clinic College of Medicine, Rochester, USA, 2University of California San Diego, La Jolla, USA, 3Atlanta Gastroenterology Associates, Atlanta, USA, 4Humanitas University, Milan, Italy, 5Takeda Development Center Americas Inc., Cambridge, USA, 6University Hospitals Leuven, Leuven, Belgium
Vedolizumab is a gut-selective, humanised, α4β7 integrin monoclonal antibody approved for intravenous (IV) administration to patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD). A subcutaneous (SC) formulation is in development as maintenance therapy. Here, we evaluate clinical response to 2 or 3 doses of vedolizumab IV induction therapy in the phase 3 VISIBLE 1 (UC; NCT02611830) and VISIBLE 2 (CD; NCT02611817) vedolizumab SC maintenance trials.
In both trials, patients received open-label vedolizumab 300 mg IV induction therapy at Weeks 0 and 2. At Week 6, clinical responders were randomised into the SC maintenance phase and nonresponders were given a third IV 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 ≤1 point at both time points. Clinical response for CD was a >70-point decrease in CD Activity Index score from Week 0. Safety of vedolizumab IV 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).
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 IV 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 IV infusions. In VISIBLE 1, treatment-emergent adverse events (TEAEs, 62.9% of patients; 17% treatment-related) and serious TEAEs (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.
Vedolizumab IV 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 IV induction was consistent with previous reports.