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Atorvastatin Therapy Mediated Some Aspects of Disease Activity in Patients with Rheumatoid Arthritis

Atorvastatin appears to significantly reduce swollen joints and suppress acute-phase variables in patients with active inflammatory rheumatoid arthritis despite ongoing therapy with disease-modifying antirheumatic drugs (DMARDs).

Iain B. McInnes, Centre for Rheumatic Diseases, Glasgow Royal Infirmary, United Kingdom, and colleagues assessed disease activity in 116 patients, median age of 56 years, over 6 months after equal randomisation to 40 mg atorvastatin or placebo in a double-blind trial.

The patients had a median duration of disease of 11.5 years, and maintained DMARD dosages during the study period. Intramuscular or intra-articular corticosteroid injection was permitted during the study except during the 4 weeks prior to clinical assessment. The treatment groups were generally comparable except in visual analogue score and patient global assessment values which were lower at baseline in the atorvastatin group.

The investigators analysed data according to intention-to-treat so and considered those not completing 6 months of therapy as non-responders. The primary outcomes were a change in disease activity score (DAS28) and the proportion of patients meeting European League Against Rheumatism (EULAR) response criteria.

At 6 months, 31% of the patients allocated to atorvastatin, compared with 10% of the placebo group, achieved DAS28 EULAR response. DAS28 improved significantly in the atorvastatin group, -0.50, compared with 0.03 in the placebo group. Adjustment for methotrexate use, which was higher in the atorvastatin group, did not change the significance of the reduction in the DAS28 (P = .007).

Acute-phase reactants, including C-reactive protein and erythrocyte sedimentation declined by 50% and by 28%, respectively, in the atorvastatin treated patients relative to placebo. Adjustment for methotrexate use did not alter these findings.

The mean difference in swollen joint count was -2.16, also in favour of the atorvastatin group. The patients treated with atorvastatin also showed a modification of vascular risk factors. Also, adverse events were similar between groups.

Additionally, 53 patients in the atorvastatin group compared with 45 in the placebo group completed the study to 6 months, "further indicating the beneficial effect of statin use and tolerability of therapy," the authors note.

"Although the magnitude of change is modest, the significant reduction in DAS28 provides proof of concept that pathways targeted by statins offer therapeutic opportunity in inflammatory disease," the authors conclude, adding "Further studies are now needed to establish what benefit is conferred by inclusion of statins on long-term outcomes in rheumatoid arthritis."

Lancet 2004;363:2015-21

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