Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial

McCarey, D.W., McInnes, I.B. , Madhok, R., Hampson, R., Scherbakov, O., Ford, I. , Capell, H. and Sattar, N. (2004) Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet, 363(9426), pp. 2015-2021. (doi:10.1016/S0140-6736(04)16449-0) (PMID:15207950)

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Abstract

BACKGROUND: Rheumatoid arthritis is characterised by inflammatory synovitis, articular destruction, and accelerated atherogenesis. HMG-CoA (3-hydroxy-3-methylglutarylcoenzyme A) reductase inhibitors (statins) mediate clinically significant vascular risk reduction in patients without inflammatory disease and might have immunomodulatory function. We postulated that statins might reduce inflammatory factors in rheumatoid arthritis and modify surrogates for vascular risk.

METHODS: 116 patients with rheumatoid arthritis were randomised in a double-blind placebo-controlled trial to receive 40 mg atorvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug therapy. Patients were followed up over 6 months and disease activity variables and circulating vascular risk factors were measured. Coprimary outcomes were change in disease activity score (DAS28) and proportion meeting EULAR (European League Against Rheumatism) response criteria. Analysis was by intention to treat.

FINDINGS: At 6 months, DAS28 improved significantly on atorvastatin (-0.5, 95% CI -0.75 to -0.25) compared with placebo (0.03, -0.23 to 0.28; difference between groups -0.52, 95% CI -0.87 to -0.17, p=0.004). DAS28 EULAR response was achieved in 18 of 58 (31%) patients allocated atorvastatin compared with six of 58 (10%) allocated placebo (odds ratio 3.9, 95% CI 1.42-10.72, p=0.006). C-reactive protein and erythrocyte sedimentation rate declined by 50% and 28%, respectively, relative to placebo (p < 0.0001, p=0.005, respectively). Swollen joint count also fell (-2.69 vs -0.53; mean difference -2.16, 95% CI -3.67 to -0.64, p=0.0058). Adverse events occurred with similar frequency in patients allocated atorvastatin and placebo.

INTERPRETATION: These data show that statins can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Ford, Professor Ian and Capell, Dr Hilary and McCarey, Dr David and Madhok, Dr Rajan and Sattar, Professor Naveed
Authors: McCarey, D.W., McInnes, I.B., Madhok, R., Hampson, R., Scherbakov, O., Ford, I., Capell, H., and Sattar, N.
Subjects:R Medicine > RC Internal medicine
R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Lancet
Publisher:The Lancet Publishing Group
ISSN:0140-6736
ISSN (Online):1474-547X

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