Metabolic and Cardiovascular Benefits of Hydroxychloroquine in Patients with Rheumatoid Arthritis: a Systematic Review and Meta-analysis

Objective: Cardiovascular disease (CVD) is the leading cause of mortality in patients with rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) has been shown to improve survival rates in other inflammatory diseases. We aimed to assess the available literature on the cardiovascular impact of HCQ in patients with RA.

Methods: We systematically searched for studies evaluating the effects of HCQ on cardiovascular outcomes of known risk factors for CVD in patients with RA. Databases searched were MEDLINE (via PubMed), EMBase, Cochrane Library and the American College of Rheumatology and European League Against Rheumatism annual meetings. A meta-analysis was performed with a random-effects model, estimating mean differences (MDs), HRs and 95% CIs. Data were extracted by one investigator and independently checked by another.

Results: The literature search revealed 185 articles and abstracts of interest; further examination resulted in 16 studies fulfilling the criteria. The MDs between HCQ users and non-users in levels of total, low-density and high-density cholesterol and triglycerides were -9.8 (95% CI -14.0 to -5.6), -10.6 (95% CI -14.2 to -7.0), +4.1 (95% CI 2.2 to 6.0) and -19.2 (95% CI -27.2 to -11.1), respectively. Diabetes incidence was lower for HCQ ever users than never users (HR 0.59 (95% CI 0.49 to 0.70)). HCQ seemed to decrease insulin resistance and incidence of CVD, but data were too few for meta-analysis.

Conclusion: Besides its limited efficacy for disease activity and progression, HCQ may benefit the metabolic profile and to a lesser extent cardiovascular events in patients with RA, which suggests its usefulness combined with other conventional synthetic disease-modifying antirheumatic drugs.