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| |  HIV Drug, Maraviroc, Does Not Improve Signs, Symptoms of RA: Presented at ACR/ARHP By Liz Meszaros PHILADELPHIA -- October 18, 2009 -- Maraviroc failed to improve the signs and symptoms of rheumatoid arthritis (RA) in patients with active disease on background methotrexate therapy, according to interim study data presented here at the 2009 Annual Scientific Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP). Maraviroc is an antagonist of the human chemokine receptor 5 (CCR-5), and is approved for the treatment of patients infected with CCR-5-tropic HIV. In patients with RA, the presence of a nonfunctional receptor of the CCR-5 gene resulting from a 32-base pair deletion has been associated with reduced incidence and severity of disease. In this 12-week study, maraviroc was used to assess whether CCR-5 antagonism was safe and effective in treating RA patients taking background methotrexate. The safety/pharmacokinetic (PK) study demonstrated that maraviroc was well tolerated, and caused no drug-drug interactions with methotrexate. The proof-of-concept component was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study. One hundred ten subjects with active RA received weekly methotrexate (>=10 mg and <=25 mg) for at least 12 weeks, and had at least 6 tender and swollen joints and C-reactive protein levels of at least 7.0 mg/L. There were no significant differences between the 300 mg twice-daily maraviroc group (n = 77) and placebo (n = 33) in ACR20 responder rates when the full analysis set was used (27.27% vs 18.18%, P = .155). ACR50 and ACR70 responder rates were no different. ACR scale-measured responses, including CRP, were unchanged. The study was terminated for futility at the time of this interim analysis. “Selective antagonism of CCR-5 using maraviroc failed to improve the signs and symptoms of RA in patients with active disease receiving background methotrexate, and does not offer a meaningful therapeutic response in patients with active RA,” said lead investigator Dona Fleishaker, Pfizer, Inc., St. Louis, Missouri in a presentation on October 18. Maraviroc was, however, safe and well tolerated in the small, 16-subject safety/PK analysis, and the majority of adverse events were mild to moderate. The most common adverse events were constipation (7.8%), nausea (5.2%), fatigue (5.2%), urinary tract infection (3.9%), and respiratory tract infection (2.9%). Dr. Fleishaker noted that the HIV compound has a “black box” warning for hepatotoxicity. “We were very interested in watching the liver transaminase values.” No patients exhibited any elevations in these levels. “Results from the safety/PK section of this study demonstrated that maraviroc was well tolerated and not associated with any drug-drug interactions when used in combination with methotrexate,” concluded Dr. Fleishaker. [Presentation title: A Phase 2 Study to Assess the Efficacy and Safety of Maraviroc, a CCR-5 Antagonist in the Treatment of Rheumatoid Arthritis. Abstract 397]
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