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Safety and tolerability of antagonist anti‐human CD40 Mab ch5D12 in patients with moderate to severe Crohn's disease
Author(s) -
KASRAN A.,
BOON L.,
WORTEL C. H.,
HOGEZAND R. A.,
SCHREIBER S.,
GOLDIN E.,
BOER M.,
GEBOES K.,
RUTGEERTS P.,
CEUPPENS J. L.
Publication year - 2005
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2005.02526.x
Subject(s) - medicine , tolerability , cd154 , crohn's disease , cd40 , monoclonal antibody , gastroenterology , immunology , antagonist , disease , antibody , adverse effect , pharmacology , receptor , cytotoxic t cell , biochemistry , chemistry , in vitro
Summary 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.