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Title: Statins May Provide Anti-Inflammatory Benefit in Patients with Rheumatoid Arthritis

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Lancet 2004;363:2015-2021
07/05/2004 02:19:00 PM
By Emma Hitt, PhD

Statins may result in clinical anti-inflammatory benefit by modifying vascular risk factors in patients with rheumatoid arthritis, a new study suggests. Patients with rheumatoid arthritis experience inflammatory synovitis, articular destruction, and accelerated atherogenesis. Statins work, in part, by modulating lipids, but they are also thought to have broader properties, including the ability to alter inflammatory pathways and to suppress adhesion molecule expression, leucocyte cytokine release, MHC class II expression, lymphocyte and macrophage cognate interactions, and effects on reactive oxygen and nitrogen intermediate production. David W. McCarey, MD, with the Centre for Rheumatic Diseases, at the University of Glasgow, United Kingdom, and colleagues randomised 116 patients with rheumatoid arthritis to receive 40 mg atorvastatin or placebo supplementary to their disease-modifying antirheumatic drug (DMARD) regimen. Disease activity variables and circulating vascular risk factors were measured over 6 months. Primary outcome measures were change in disease activity score (DAS28) and proportion meeting EULAR (European League Against Rheumatism) response criteria. After 6 months, an intention to treat analysis found that the DAS28 improved significantly in the group receiving atorvastatin compared with placebo ([P = .004). Of the 58 patients taking atorvastatin, 18 (31%) patients achieved the DAS28 EULAR response compared with only 6 of 58 (10%) taking placebo (odds ratio 3.9; P = .006). In addition, C-reactive protein declined by 50% (P < .0001) and erythrocyte sedimentation rate declined by 28% (P = .005) in patients taking atorvastatin versus those taking placebo. Swollen joint count was also reduced in the atorvastatin group (P = .0058). Adverse events were similar between groups. Furthermore, no significant liver function or muscle abnormality was detected in those taking atorvastatin. More patients in the placebo group received intra-articular or intramuscular administration of triamcinolone than in the atorvastatin group. "We have shown marked suppression with atorvastatin of acute-phase variables and a significant reduction in swollen joint count in patients with rheumatoid arthritis presenting with active disease despite existing DMARD therapy," Dr. McCarey and colleagues note. "Although not indicative for first line use," they add, "this effect of atorvastatin could prove beneficial in the context of DMARD combination design, in which a statin offers both vascular protective and adjunctive immune modulatory potential."

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