ABSTRACT: To compare the risk of incident hyperlipidemia in early rheumatoid arthritis (RA) patients after initiation of various disease-modifying antirheumatic drugs (DMARDs).We conducted a cohort study using insurance claims data (2001-2012) in early RA patients. Early RA was defined by the absence of any RA diagnosis or DMARD prescriptions for 12 months. Four mutually exclusive groups were defined based on DMARD initiation: tumor necrosis factor ? (TNF?) inhibitors ± nonbiologic (nb) DMARDs, methotrexate (MTX) ± nonhydroxycholorquine nbDMARDs, hydroxychloroquine ± non-MTX nbDMARDs, and other nbDMARDs only. The primary outcome was incident hyperlipidemia, defined by a diagnosis and a prescription for a lipid-lowering agent. For the subgroup of patients with laboratory results available, change in lipid levels was assessed. Multivariable Cox proportional hazard models and propensity score (PS) decile stratification with asymmetric trimming were used to control for confounding.Of the 17,145 early RA patients included in the study, 364 developed incident hyperlipidemia. The adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) for hyperlipidemia were 1.41 (95% CI 0.99, 2.00) for TNF? inhibitors, 0.81 (95% CI 0.63, 1.04) for hydroxychloroquine, and 1.33 (95% CI 0.95, 1.84) for other nbDMARDs compared with MTX in the full cohort, while HRs for the PS trimmed cohort were 1.18 (95% CI 0.80, 1.73), 0.75 (95% CI 0.58, 0.98), and 1.41 (95% CI 1.01, 1.98), respectively. In the subgroup analysis, hydroxychloroquine use showed significant reduction in low-density lipoprotein (-8.9 mg/dl, 95% CI -15.8, -2.0), total cholesterol (-12.3 mg/dl, 95% CI -19.8, -4.8) and triglyceride levels (-19.5 mg/dl, 95% CI -38.7, -0.3) from baseline compared with MTX.Use of hydroxychloroquine may be associated with a lower risk of hyperlipidemia among early RA patients.