Hydroxychloroquine for RA Boosts Metabolic, Cardiovascular Profile


The agent reduces cardiovascular events but has only a moderate effect on RA disease progression and activity.

In patients with rheumatoid arthritis, hydroxychloroquine decreases modifiable risk factors for cardiovascular disease, including lipid profile, diabetes incidence, and glycosylated hemoglobin levels.

Hydroxychloroquine reduces the incidence of cardiovascular events but has only a moderate effect on RA disease progression and disease activity and is not used as monotherapy.

Patients with rheumatoid arthritis are at higher risk for cardiovascular disease and death compared with the general population. Hydroxychloroquine has been shown to improve survival rates in other inflammatory diseases, such as systemic lupus erythematosus.

As a treatment for rheumatoid arthritis, hydroxychloroquine has a modest effect, but it can be used in combination therapy and may act synergistically with methotrexate.

Claire Rempenault and fellow researchers in France sought to uncover the impact of hydroxychloroquine on the metabolic profile and incidence of cardiovascular disease in patients with rheumatoid arthritis. They presented their findings in a recent Annals of the Rheumatic Diseases article.

The study

The authors conducted a systematic review and meta-analysis of the literature to look at hydroxychloroquine and rheumatoid arthritis.

Ultimately, 16 studies were included in the systematic review and 9 studies in the meta-analysis for lipid rates and diabetes incidence.

The results

• Lipid profiles were better in hydroxychloroquine patients; total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), and triglycerides (TG) were −9.8 mg/dL (95% confidence interval [CI], −14.0 to −5.6); −0.25 mmol/L, −10.6 mg/dL (95% CI, −14.2 to −7.0); +4.1 mg/dL (2.2; 6.0) (+0.10 mmol/L); and −19.1 mg/dL (95% CI, −27.2 to −11.1), respectively.

• After initiation of hydroxychloroquine, the average decrease in level of TC, LDL, and TG was −13.1 mg/dL (95% CI, −20.9 to −5.3) (−0.34 mmol/L); −12.3 mg/dL (95% CI, −20.2 to −4.6) (−0.32 mmol/L); and −12.5 mg/dL (95% CI, −28.9 to 3.9) (−0.14 mmol/L), respectively, and mean increase in HDL level was 1.6 mg/dL (95% CI, −0.96 to 4.3) (+0.04 mmol/L).

• The incidence of diabetes was lower in patients with rheumatoid arthritis who were receiving hydroxychloroquine than in those who were not (pooled hazard ratio, 0.59 [95% CI, 0.49 to 0.70]).

• Hemoglobin A1c was reduced in patients with rheumatoid arthritis who were taking hydroxychloroquine (−0.19±0.13%).

• Overall cardiovascular risk was reduced in patients with rheumatoid arthritis taking hydroxychloroquine (retrospective study odds ratio [OR], 0.27 [95% CI, 0.16 to 0.46]; case-control study adjusted OR, 0.45 [95% CI, 0.10 to 2.0]).

• In a recent retrospective study, hydroxychloroquine was associated with a reduced risk of cardiovascular disease (adjusted hazard ratio [HR], 0.60 [95% CI, 0.41 to 0.94], p=0.02) as well as a reduced incidence of composite coronary artery disease, stroke, and transient ischemic attack (adjusted HR, 0.67 [95% CI, 0.42 to 1.070], p=0.09).

Implications for physicians

• Because of a positive effect on both metabolic parameters and cardiovascular risk in patients with rheumatoid arthritis, hydroxychloroquine should be considered in combination therapy, especially in patients at higher risk for diabetes and cardiovascular disease.

• Patients who have rheumatoid arthritis with hyperglycemia, hyperlipidemia, or baseline cardiovascular risk factors may benefit from hydroxychloroquine treatment irrespective of the treatment for rheumatoid arthritis.

• Hydroxychloroquine is well tolerated and as such is a safe and well-established adjunct to other disease-modifying antirheumatic drugs in the treatment of patients with rheumatoid arthritis.


Rempenault C, Combe B, Barnetche T, et al. “Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis.” Ann Rheum Dis. 2017 Sep 25. pii: annrheumdis-2017-211836. doi: 10.1136/annrheumdis-2017-211836. [Epub ahead of print]

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