Background/Purpose: Cardiovascular disease is a significant comorbidity among RA patients. As such, dyslipidemia and the effect of DMARD therapy on lipid profiles is an important consideration in RA management. Previous reports show that suppression of systemic inflammation, particularly in early RA, leads to increased cholesterol levels. While the magnitude of this effect appears to vary by treatment and populations studied, there has been limited study of this effect in the important subgroup of MTX suboptimal responders with subsequent escalation of DMARD therapy.

Methods:   Statistical analyses were performed using data from the Rheumatoid Arthritis Comparison of Active Therapies (RACAT) trial. Patients with active RA despite treatment with MTX were randomized to receive triple therapy (MTX/HCQ/SSZ) or MTX/etanercept (ET). Those showing inadequate response were crossed over at 24 weeks. Using banked serum from baseline, 24, and 48 weeks (n=204), levels of total cholesterol (TC), LDL, VDL, HDL, and triglyceride (TG) were measured. Changes in lipids between each time point were examined using generalized estimating equations (GEE models), adjusting for baseline characteristics and DAS-28. To further examine the effect of treatment on lipid profiles, we compared changes in the first 24 weeks of exposure to each treatment (patients started on triple therapy plus those crossed over to triple therapy at 24 weeks versus patients started on MTX/ET plus those crossed over to MTX/ET at 24 weeks) using additional GEE models.

Results:   There were significant decreases in VDL, TG, and TC:HDL ratio and a significant increase in HDL over observation after controlling for baseline characteristics (Table). With further adjustment for DAS-28, effect sizes were reduced and no longer significant. Comparing the effect of MTX/ET to triple therapy on lipids over the first 24 weeks of exposure, there was a larger decrease in VDL with triple therapy (β=3.32 mg/dL; p=0.037). In adjusted models, the effect size was largely unchanged with p-values of borderline significance (3.08, p=0.056 adjusting for baseline characteristics; 3.10, p=0.055 adjusting for baseline characteristics + DAS-28).

Conclusion:   These data show favorable changes in VDL, HDL, TG, and the TC:HDL ratio in RA patients after escalating therapy following treatment failure with MTX. This is driven largely by improvement in DAS-28, differing from previous reports where suppression of disease activity is associated with elevation in cholesterol levels. In addition, data here show a trend toward more favorable levels of VDL with triple therapy relative to MTX/ET, supporting previous work showing more favorable lipid profiles with triple therapy in early RA. Additional research is needed to elucidate the clinical implications of these changes in lipids, as well as the effect of altered lipoprotein function in RA. Table 1.