A multicenter, open-label clinical trial published in Medicine (Baltimore) has found that a low-dose combination of rosuvastatin and ezetimibe is both effective and safe in lowering low-density lipoprotein cholesterol (LDL-C) levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The only independent predictor of treatment response was the baseline LDL-C level.
The study enrolled adults aged 19 years and older with a confirmed diagnosis of either RA or OA involving the hands or knees. Participants met eligibility criteria for treatment with rosuvastatin/ezetimibe based on clinical indications for primary hypercholesterolemia or mixed dyslipidemia, in accordance with Korean national health insurance guidelines. All patients received a fixed-dose combination of rosuvastatin 5 mg and ezetimibe 10 mg daily for 12 weeks. At the end of the treatment period, 79.7% of patients with rheumatoid arthritis and 70.1% of those with osteoarthritis achieved at least a 50% reduction in LDL-C levels from baseline. The difference in response between the two groups was not statistically significant (P = 0.1086). Safety outcomes were also comparable across both groups, with no significant adverse events noted.
Further statistical analysis showed that baseline LDL-C level was the only independent factor predicting the degree of cholesterol reduction. Variables such as disease activity score, C-reactive protein (CRP), age, body mass index (BMI), smoking status, hypertension, diabetes mellitus, and glucocorticoid use did not show a significant association with treatment response in either univariate or multivariate regression models.
Cardiovascular disease (CVD) remains the leading cause of death in patients with rheumatoid arthritis, with prevalence significantly higher than in the general population. Interestingly, despite an increased risk of CVD, patients with RA often present with paradoxically lower levels of total cholesterol (TC), LDL-C, and high-density lipoprotein cholesterol (HDL-C)—a phenomenon attributed to chronic systemic inflammation affecting lipid metabolism.
Rosuvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is capable of reducing LDL-C levels by up to 55%. It also raises HDL-C levels by approximately 6%, lowers triglycerides (TG) by 15% or more, and reduces cholesterol accumulation within atherosclerotic plaques. Beyond lipid-lowering, rosuvastatin exhibits pleiotropic effects such as anti-inflammatory, antioxidant, and endothelial-protective properties. Ezetimibe, the only drug in its class, acts as a Niemann-Pick C1-Like 1 (NPC1L1) inhibitor that blocks cholesterol absorption at the intestinal brush border. It can reduce cholesterol absorption by up to 67%, leading to a 15–20% reduction in LDL-C. Ezetimibe also modestly increases HDL-C by approximately 3% and has minimal impact on triglyceride levels.
The findings underscore that combination therapy with low-dose rosuvastatin and ezetimibe is a safe and effective strategy for lowering LDL-C levels in both inflammatory (RA) and non-inflammatory (OA) arthritis populations. The response to treatment appeared to be driven by initial cholesterol levels rather than inflammatory disease status. These insights may help guide lipid management in patients with arthritis, especially those at elevated cardiovascular risk.
References
- Bak SH, Lee KA, Kim SS, Kim SH, Hong SJ, Kim HS. Efficacy and safety of low-dose rosuvastatin/ezetimibe for dyslipidemia in patients with rheumatoid arthritis or osteoarthritis. Medicine (Baltimore). 2025 Jul 4;104(27):e43133.
- Yan J, Yang S, Han L, Ba X, Shen P, Lin W, Li T, Zhang R, Huang Y, Huang Y, Qin K, Wang Y, Tu S, Chen Z. Dyslipidemia in rheumatoid arthritis: the possible mechanisms. Front Immunol. 2023 Oct 25;14:1254753.
- Chilbert MR, VanDuyn D, Salah S, Clark CM, Ma Q. Combination Therapy of Ezetimibe and Rosuvastatin for Dyslipidemia: Current Insights. Drug Des Devel Ther. 2022 Jul 7;16:2177-2186.