Although research regarding the increased cardiovascular (CV) morbidity and mortality in rheumatoid arthritis (RA) has burgeoned in recent years, the need remains for a better understanding of the effects of widely used DMARDs on CV risk and risk factors in RA patients. These authors set out to evaluate the long-term changes in cholesterol levels in patients with early RA who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial.
They describe the long-term effects of disease activity, DMARD use and patient characteristics on cholesterol levels in a large clinical trial of patients with early RA, demonstrating two major points: 1) suppression of RA-related inflammation is associated with increases in cholesterol levels, which are highest in the early phase of therapy regardless of treatment, and 2) use of triple therapy is associated with decreases in the total cholesterol:high-density lipoprotein (HDL) cholesterol ratio over long-term follow-up. The effects of these cholesterol changes on CV events in patients with RA warrant further study.
Methods: Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and HDL cholesterol were analyzed in 416 patients participating in the TEAR trial during 102 weeks of follow-up. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated-measures analysis with mixed-effect linear models to model within-subject covariance over time.
Results: Mixed-effect models controlling for traditional CV risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28-joint Disease Activity Score, the C-reactive protein level or the erythrocyte sedimentation rate were associated with increases in levels of HDL cholesterol, LDL cholesterol and total cholesterol in all treatment groups (P<0.001–0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol and higher ratios of total cholesterol:HDL cholesterol (P<0.001 for all) compared with MTX monotherapy or MTX plus etanercept therapy over the two-year follow-up.
Conclusion: Decreases in RA disease activity over long-term follow-up were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies. The use of triple therapy during two years of follow-up was associated with higher HDL cholesterol levels, lower LDL cholesterol levels and lower total cholesterol:HDL cholesterol ratios compared with those observed in patients who received MTX monotherapy or MTX plus etanercept combination therapy. Additional studies are needed to assess the effects of these cholesterol changes on CV events in patients with RA.