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

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Lancet. 2004 Jun 19;363(9426):2015-21.

Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind,

randomised placebo-controlled trial.

McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I,

Capell HA, Sattar N.

Centre for Rheumatic Diseases, University of Glasgow, Glasgow Royal

Infirmary, Glasgow, UK.

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.

PMID: 15207950

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