Title: A phase I study of visilizumab a humanized anti-CD3, monoclonal antibody, in severe steroid-refractory ulcerative colitis
Authors: Plevy, Scott ×
Salzberg, Bruce
Van Assche, Gert
Regueiro, Miguel
Hommev, Daniel
Sandborn, William
Hanauer, Stephen
Targan, Stephan
Mayer, Lloyd
Mahadevan, Uma
Frankel, Matthew
Lowder, James #
Issue Date: Nov-2007
Publisher: W.B. Saunders
Series Title: Gastroenterology vol:133 issue:5 pages:1414-1422
Abstract: Background & Aims: To evaluate the safety and biological activity of visilizumab (a humanized anti-CD3 monoclonal antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. Methods: In this open-label phase 1 study, 32 subjects received visilizumab at a dose of 10 or 15 mu g/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index < 10 with a minimum decrease of 3 points; remission was <4 points. Endoscopic remission was a Mayo endoscopic subscore of 0 or 1. Results: Eight patients received 15 mu g/kg visilizumab. Because of dose-limiting toxicities (T-cell recovery >30 days in 2 of 8 patients), the dose was reduced to 10 mu g/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-mu g/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4(+) T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. Conclusions: Visilizumab had an acceptable safety profile at the 10-mu g/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid-refractory ulcerative colitis.
ISSN: 0016-5085
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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