Prospective randomized open-label multicenter phase I/II dose escalation trial of visilizumab (HuM291) in severe steroid-refractory ulcerative colitis
✍ Scribed by Daniel C. Baumgart; Stephan R. Targan; Axel U. Dignass; Lloyd Mayer; Gert van Assche; Daan W. Hommes; Stephen B. Hanauer; Uma Mahadevan; Walter Reinisch; Scott E. Plevy; Bruce A. Salzberg; Alan L. Buchman; Grigor M. Mechkov; Zahariy A. Krastev; James N. Lowder; Matthew B. Frankel; William J. Sandborn
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 232 KB
- Volume
- 16
- Category
- Article
- ISSN
- 1078-0998
No coin nor oath required. For personal study only.
✦ Synopsis
Background:
Visilizumab is a humanized igg(2) monoclonal anti-cd3 antibody. we evaluated its safety and dose response in severe intravenous steroid-refractory ulcerative colitis (uc).
Methods:
In all, 104 patients were treated. in stage i, 73 patients were randomly assigned to receive intravenous visilizumab 5, 7.5, 10, or 12.5 microg/kg/day for 2 consecutive days. in stage ii, 33 patients received visilizumab at the optimal clinical dose (ocd) of 5 microg/kg/day for 2 days. symptomatic response and remission were defined by the modified truelove-witts severity index. clinical response and remission were defined by the mayo score.
Results:
The rates of symptomatic response at day 15 in the 5, 7.5, 10, or 12.5 microg/kg dose groups were 71%, 70%, 50%, and 61%, respectively, in stage i and in 54% in stage ii. the symptomatic remission rates were 35%, 5%, 22%, and 11% in stage i and 18% in stage ii. the rates of clinical response at day 30 in the 5, 7.5, 10, or 12.5 microg/kg dose groups were 71%, 65%, 50%, and 67%, respectively, in stage i and 55% in stage ii. the clinical remission rates were 6%, 5%, 0%, and 11% in stage i and 6% in stage ii. all patients experienced adverse events. serious adverse events included abdominal abscess, cytomegalovirus infection, atrial fibrillation, herpes zoster, and esophageal candidiasis.
Conclusions:
Treatment with visilizumab induced symptomatic response and clinical response. results with 5 microg/kg/day were similar to those observed with higher doses.