Background and aims Pilot studies with visilizumab, a humanised monoclonal antibody to CD3, suggest efficacy for corticosteroid-refractory ulcerative colitis (UC). A placebo-controlled trial was warranted.
Methods A randomised, double-blind, placebo-controlled study evaluated the efficacy of visilizumab induction treatment in 127 patients with severely active UC despite treatment with ≥5 days of intravenous corticosteroids. Patients received placebo or visilizumab 5 μg/kg intravenously on days 1 and 2. Corticosteroids were tapered according to disease activity. Patients were followed up for 90 days. The primary end point was induction of response at day 45. Secondary end points included remission and mucosal healing at day 45, symptomatic response at day 15 and colectomy.
Results Response at day 45 occurred in 55% of patients receiving visilizumab compared with 47% of those who received placebo (p=0.475). Remission at day 45 occurred in 8% of patients receiving visilizumab compared with 9% of those who received placebo (p=0.704). Mucosal healing at day 45 occurred in 29% of patients receiving visilizumab compared with 26% of those who received placebo (p=0.799). Symptomatic response at day 15 occurred in 82% of patients receiving visilizumab compared with 74% of those who received placebo (p=0.244). Colectomy was performed in 18% of patients receiving visilizumab compared with 7% of those who received placebo (p=0.130). Cardiac disorders and vascular disorders occurred more frequently in the patients who received visilizumab.
Conclusion Visilizumab at a dose of 5 μg/kg for two consecutive days was not effective for severe, corticosteroid-refractory UC and was associated with increased cardiac and vascular adverse events.
(Registered at http://www.clinicaltrials.govNCT00279422/).
- ulcerative colitis
- T cells
- randomised controlled study
- inflammatory bowel disease
- monoclonal antibody
- induction therapy
- antibody targeted therapy
- clinical trials
- steroid-sparing efficacy
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Funding Supported by a research grant from Facet Biotech (previously PDL BioPharma), Redwood City, California, USA.
Competing interests WS, JFC, DH, LM, ST, SRT, GV and STa have served as consultants and received research support from PDL BioPharma. PS and DCB have received research support from PDL BioPharma, MF and JNL are former employees of PDL BioPharma.
Ethics approval This multicentre study was conducted globally at 75 sites in 14 countries (Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Netherlands, Norway, Slovakia, Ukraine, United States). The institutional review board or ethics committee at each site approved the protocol. All patients gave written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.