William J Sandborn1, Filip Baert2, Silvio Danese3, Željko Krznarić4, Taku Kobayashi5, Xiaopan Yao6, Jingjing Chen6, Maria Rosario6, Siddharth Bhatia7, Krisztina Kisfalvi6, Geert D'Haens8, Séverine Vermeire9. 1. Division of Gastroenterology, University of California-San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu. 2. Department of Gastroenterology, AZ Delta, Roeselare, Belgium. 3. Gastrointestinal Immunopathology, Humanitas University, Italy. 4. Division of Gastroenterology and Hepatology, University Hospital Centre Zagreb, Zagreb, Croatia. 5. Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan. 6. Takeda Development Center Americas Inc, Cambridge, Massachusetts. 7. Takeda International, London, UK. 8. Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands. 9. Department of Clinical and Experimental Medicine, University Hospitals Leuven, Leuven, Belgium.
Abstract
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. Subcutaneous vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis. 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 ulcerative colitis 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 end point was clinical remission at week 52, which was defined as a total Mayo score of ≤2 and no subscore >1. RESULTS: Among the randomized 216 patients, 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% confidence interval, 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 ulcerative colitis who had a clinical response to intravenous vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov ID: NCT02611830; EudraCT 2015-000480-14.
RCT Entities:
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. Subcutaneous vedolizumab was investigated as maintenance treatment in patients with moderately to severely active ulcerative colitis. 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 ulcerative colitis 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 end point was clinical remission at week 52, which was defined as a total Mayo score of ≤2 and no subscore >1. RESULTS: Among the randomized 216 patients, 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% confidence interval, 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 ulcerative colitis who had a clinical response to intravenous vedolizumab induction therapy. It has a favorable safety and tolerability profile. ClinicalTrials.gov ID: NCT02611830; EudraCT 2015-000480-14.
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Authors: Wan Sun; Blair Fennimore; Dawn B Beaulieu; Razvan Arsenescu; Adam C Stein; Jingjing Chen; Tiffany Lin; Sonya McKnight; Harisha Kadali; Maria Rosario; Richard A Lirio Journal: Clin Pharmacokinet Date: 2021-02-05 Impact factor: 6.447
Authors: HoUng Kim; Rieke Alten; Fraser Cummings; Silvio Danese; Geert D'Haens; Paul Emery; Subrata Ghosh; Cyrielle Gilletta de Saint Joseph; JongHyuk Lee; James O Lindsay; Elena Nikiphorou; Ben Parker; Stefan Schreiber; Steven Simoens; Rene Westhovens; Ji Hoon Jeong; Laurent Peyrin-Biroulet Journal: MAbs Date: 2021 Jan-Dec Impact factor: 5.857