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Highly Accessed Editorial

What is the future of CCR5 antagonists in rheumatoid arthritis?

Tsutomu Takeuchi* and Hideto Kameda

Author Affiliations

Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjyuku, Toky 160-8582, Japan

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Arthritis Research & Therapy 2012, 14:114  doi:10.1186/ar3775


See related research by Fleishaker et al., http://arthritis-research.com/content/14/1/R11

Published: 30 March 2012

Abstract

Fleishaker and colleagues reported on a double-blind placebo controlled clinical trial of a C-C chemokine-receptor type 5 (CCR5) antagonist, maraviroc, in rheumatoid arthritis (RA) patients with inadequate response to methotrexate, showing that it was ineffective. Two additional CCR5 antagonists, SCH351125 and AZD5672, also failed to demonstrate clinical efficacy. In addition, CCR5-blocking antibodies could not inhibit synovial fluid-induced monocyte chemotaxis. Thus, CCR5 appears not to be a desirable target in RA treatment. Given the multiple functions of CCR5, redundancies in the chemokine system, and patient selection in the trial, we overview the recent understanding for chemokine receptor blockade in the treatment of RA