Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis.
Gastroenterology. 2019 Aug 27;:
Authors: Sandborn WJ, Baert F, Danese S, Krznarić Ž, Kobayashi T, Yao X, Chen J, Rosario M, Bhatia S, Kisfalvi K, D’Haens G, Vermeire S
BACKGROUND & AIMS: Maintenance treatment with vedolizumab, a monoclonal antibody that inhibits the gut-selective α4β7 integrin, is administered intravenously. Some patients might prefer a subcutaneous formulation of vedolizumab for maintenance treatment. Vedolizumab SC was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis (UC).
METHODS: We performed a phase 3, double-blind, double-dummy trial, at 141 sites in 29 countries, from December 18, 2015 through August 21, 2018. Patients with moderately to severely active UC received open-label treatment with intravenous vedolizumab 300 mg at weeks 0 and 2. At week 6, patients with clinical response were randomly assigned maintenance treatment with subcutaneous vedolizumab (108 mg) every 2 weeks, intravenous vedolizumab 300 mg every 8 weeks, or placebo. The primary endpoint was clinical remission at week 52, defined as a total Mayo score of 2 or lower and no subscore greater than 1.
RESULTS: Among 216 patients randomly assigned to groups, clinical remission at week 52 was achieved by 46.2%, 42.6%, and 14.3% of patients in the subcutaneous vedolizumab, intravenous vedolizumab, and placebo groups, respectively (subcutaneous vedolizumab vs placebo: Δ32.3%; 95% CI, 19.7%-45.0%; P<.001). The subcutaneous vedolizumab group also had greater endoscopic improvement and durable clinical response at week 52 compared with placebo (both P<.001). The incidence of injection-site reactions was more frequent in patients given subcutaneous vedolizumab (10.4%) than intravenous vedolizumab (1.9%) or placebo (0%); these were not treatment limiting, most were mild, and none resulted in discontinuation. Subcutaneous and intravenous vedolizumab safety profiles were otherwise similar.
CONCLUSIONS: Subcutaneous vedolizumab is effective as maintenance therapy in patients with moderately to severely active UC who had a clinical response to intravenous vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov no: NCT02611830; EudraCT 2015-000480-14.
PMID: 31470005 [PubMed – as supplied by publisher]