Statins were developed for their antilipid properties, but they also act as anti-inflammatories. In vitro studies indicate that statins may be beneficial in treating rheumatoid arthritis. McCarey and colleagues studied the clinical effects of atorvastatin on patients with rheumatoid arthritis in a double-blind, randomized, placebo-controlled trial.
One hundred and sixteen adults with continued active rheumatoid arthritis after at least three months of adequate disease-modifying antirheumatic drug therapy participated in the study. Active disease was defined as at least six swollen joints and at least two other features (six tender joints, 30 minutes or more of morning stiffness, or erythrocyte sedimentation rate [ESR] of 28 mm per hour or higher). Exclusion criteria included diabetes, elevated coronary heart disease risk, familial hypercholesterolemia, steroid intake of 10 mg or more per day, and significant renal insufficiency. Patients remained on all therapy for rheumatoid arthritis and other conditions throughout the study. After assessment, patients were randomized to receive 40 mg of atorvastatin or placebo. The primary outcome was change in the DAS28 scale, a validated composite disease activity score that incorporates ESR, visual analog score for pain, and number of swollen or tender joints. Additional outcomes included health assessment questionnaires, C-reactive protein, plasma lipids, and endothelial function markers. Physicians assessed patients after three and six months of therapy; evaluation included screening for changes in liver and kidney function.
The two groups were generally comparable on entry to the study, but pain scores and global assessments were slightly lower in the atorvastatin group. At six months, DAS28 was significantly reduced in the atorvastatin group compared with placebo. Thirty-one percent of the atorvastatin group achieved moderate or good DAS28 response compared with only 10 percent of the placebo group. The atorvastatin group also showed significant improvements in acute-phase reactants. Levels of C-reactive protein and ESR declined by 50 and 28 percent respectively in patients receiving atorvastatin compared with those receiving placebo. These results remained consistant after adjusting for all significant variables. Other indicators of disease activity, particularly the number of swollen joints, also improved during atorvastatin therapy. Very few adverse events occurred in either group. More atorvastatin patients completed the study than placebo patients (53 out of 58 compared with 45 out of 58, respectively). More placebo patients received intramuscular or intra-articular steriod injections during the study.
The authors conclude that atorvastatin was associated with a modestly beneficial but clinically useful effect in patients with rheumatoid arthritis. They speculate that statins provide vascular protective and adjunctive immune-modifying effects to disease-modifying antirheumatic drug therapy and could be effective in treating chronic inflammatory diseases.