Journal
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Volume 22, Issue 2, Pages 111-122Publisher
WILEY
DOI: 10.1111/j.1365-2036.2005.02526.x
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Background: The ligation of CD40 by CD154 is a critical step in the interaction between APC and T cells. In animals, antagonizing CD40L-CD40 has been shown to reduce the severity of several autoimmune and inflammatory disorders, including experimental colitis. Aim: To investigate tolerability and safety of an antagonist chimeric monoclonal anti-human CD40 antibody (ch5D12) for treatment of Crohn's disease. Method: ch5D12 was administrated to 18 patients with moderate to severe Crohn's disease in a single dose, open-label dose-escalation phase I/IIa study. Results: ch5D12 plasma concentrations increased dose-dependently after infusion. Two patients developed an anti-ch5D12 antibody response. Overall response and remission rates were 72 and 22%, respectively with no evidence for a dose-response effect. Treatment with ch5D12 reduced microscopic disease activity and intensity of the lamina propria cell infiltrate, but did not alter percentages of circulating T and B cells. ch5D12 was well tolerated, although some patients experienced headache, muscle aches, or joint pains, which may have been related to the study drug. Conclusions: Antagonizing CD154-CD40 interactions with ch5D12 is a promising therapeutic approach for remission induction in Crohn's disease.
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