Bruce E Sands1, Brian G Feagan2, Paul Rutgeerts3, Jean-Frédéric Colombel4, William J Sandborn5, Richmond Sy6, Geert D'Haens7, Shomron Ben-Horin8, Jing Xu9, Maria Rosario9, Irving Fox9, Asit Parikh10, Catherine Milch9, Stephen Hanauer11. 1. The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: bruce.sands@mssm.edu. 2. Robarts Clinical Trials Inc, and Robarts Research Institute, Department of Medicine, and Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada. 3. Department of Gastroenterology, University Hospital Gasthuisberg and Katholieke Universiteit, Leuven, Belgium. 4. The Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; Département d'Hépato-Gastroentérologie et Centre d'Investigations Cliniques, Centre Hospitalier Régional Universitaire de Lille, Université Lille Nord de France, Lille, France. 5. Division of Gastroenterology, University of California San Diego, La Jolla, California. 6. Department of Gastroenterology, University of Ottawa, Ottawa, Ontario, Canada. 7. Department of Gastroenterology, Inflammatory Bowel Disease Centre of the Academic Medical Centre, Amsterdam, the Netherlands. 8. Department of Gastroenterology, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 9. Takeda Pharmaceuticals International Co, Cambridge, Massachusetts. 10. Takeda Pharmaceuticals International, Inc, Deerfield, Illinois. 11. Division of Gastroenterology, The University of Chicago Medical Center, Chicago, Illinois.
Abstract
BACKGROUND & AIMS: There is an increasing need for new treatments for patients with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double-blind trial to evaluate the efficacy and safety of vedolizumab, an antibody against the integrin α4β7, as induction therapy. METHODS:Patients with moderately to severely active CD (CD activity index [CDAI] score, 220-400 points) were assigned randomly to groups given vedolizumab (300 mg) or placebo intravenously at weeks 0, 2, and 6. The primary analysis involved 315 patients with previous TNF antagonist failure (ie, an inadequate response to, loss of response to, or intolerance of ≥1 TNF antagonists); we determined the proportion of patients in clinical remission (CDAI, ≤150 points) at week 6. Secondary analyses evaluated outcomes at weeks 6 and 10 in this population and in the overall population (N = 416), which included patients naive to TNF antagonist therapy (n = 101). RESULTS: Among patients who had experienced previous TNF antagonist failure, 15.2% of those given vedolizumab and 12.1% of those given placebo were in remission at week 6 (P = .433). At week 10, a higher proportion of this population given vedolizumab was in remission (26.6%) than those given placebo (12.1%) (nominal P = .001; relative risk, 2.2; 95% confidence interval, 1.3-3.6). A higher proportion of patients with previous TNF antagonist failure given vedolizumab also had a CDAI-100 response (≥100-point decrease in CDAI score from baseline) at week 6 than those given placebo (39.2% vs 22.3%; nominal P = .001; relative risk, 1.8; 95% confidence interval, 1.2-2.5). Adverse event results were similar among all groups. CONCLUSIONS:Vedolizumab was not more effective than placebo in inducing clinical remission at week 6 among patients with CD in whom previous treatment with TNF antagonists had failed. The therapeutic benefits of vedolizumab in these patients were detectable at week 10. ClinicalTrials.gov number: NCT01224171.
RCT Entities:
BACKGROUND & AIMS: There is an increasing need for new treatments for patients with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double-blind trial to evaluate the efficacy and safety of vedolizumab, an antibody against the integrin α4β7, as induction therapy. METHODS:Patients with moderately to severely active CD (CD activity index [CDAI] score, 220-400 points) were assigned randomly to groups given vedolizumab (300 mg) or placebo intravenously at weeks 0, 2, and 6. The primary analysis involved 315 patients with previous TNF antagonist failure (ie, an inadequate response to, loss of response to, or intolerance of ≥1 TNF antagonists); we determined the proportion of patients in clinical remission (CDAI, ≤150 points) at week 6. Secondary analyses evaluated outcomes at weeks 6 and 10 in this population and in the overall population (N = 416), which included patients naive to TNF antagonist therapy (n = 101). RESULTS: Among patients who had experienced previous TNF antagonist failure, 15.2% of those given vedolizumab and 12.1% of those given placebo were in remission at week 6 (P = .433). At week 10, a higher proportion of this population given vedolizumab was in remission (26.6%) than those given placebo (12.1%) (nominal P = .001; relative risk, 2.2; 95% confidence interval, 1.3-3.6). A higher proportion of patients with previous TNF antagonist failure given vedolizumab also had a CDAI-100 response (≥100-point decrease in CDAI score from baseline) at week 6 than those given placebo (39.2% vs 22.3%; nominal P = .001; relative risk, 1.8; 95% confidence interval, 1.2-2.5). Adverse event results were similar among all groups. CONCLUSIONS:Vedolizumab was not more effective than placebo in inducing clinical remission at week 6 among patients with CD in whom previous treatment with TNF antagonists had failed. The therapeutic benefits of vedolizumab in these patients were detectable at week 10. ClinicalTrials.gov number: NCT01224171.
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