Background/Purpose:   Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in rheumatoid arthritis (RA). CVD risk factor reduction, such as reducing cholesterol and plasma glucose may be beneficial for preventing CVD. Hydroxychloroquine (HCQ), a DMARD with a good safety profile and low cost, has been reported to improve lipid profiles and glucose level in RA. We aimed to examine the association between HCQ with plasma lipid and glucose levels in a large RA cohort.

Patients and Methods:   We recruited RA patients from public, private, military and Veterans Administration rheumatology clinics, and invited them for yearly follow up evaluations in which we assessed demographic and laboratory features, as well as hydroxychloroquine use.

We performed cross sectional analyses at baseline comparing fasting lipid profiles and plasma glucose between patients that were currently taking HCQ and those that were not. We subsequently used cross-sectional time- series regression models including all follow up visits, dividing patients into three groups based on hydroxychloroquine exposure: Those who had never taken HCQ during the time of our study, those who took it intermittently, and those who took it continuously.

Results:   We studied 1261 patients (938 female, 323 male) with a mean ± SD age of 59.6±11.5 years. At baseline 254 patients were on HCQ. After adjusting for age, sex, ethnicity and lipid lowering medications, patients taking HCQ had significantly lower total cholesterol (TC) (P-value= 0.001), LDL (P-value≤0.001), triglycerides (TG) (P-value=0.013), and lipid profile ratios TC/HDL (P-value ≤0.001) and LDL/HDL (P-value ≤0.001). Furthermore, HDL was significantly higher in patients taking HCQ (P-value≤0.001). Plasma glucose level was not significantly associated with HCQ.

Patients were followed for a total of 4,646 visits between 1996 and 2014, and each patient was classified by HCQ exposure. After adjusting for confounders, patients that were continuously exposed to HCQ showed significantly lower lipid levels in TC, LDL, TG, TC/HDL, LDL/HDL, and higher HDL compared to the other two groups (P-value ≤ 0.01). Plasma glucose levels were only significantly different only when comparing patients never exposed to HCQ with those that were taking it at all visits (P-value = 0.003) (Table 1).

Table 1. Pooled follow-up visits of 1,261 RA patients divided by HCQ exposure

*P-values were adjusted (P_adj) for age, sex, ethnicity and if the patients were currently on lipid lowering medications.

Conclusion: HCQ use was associated with significantly lower TC, LDL, TG, and TC/HDL and LDL/HDL ratios, and with higher HDL.  The association of HCQ with plasma glucose was not as strong as that with lipids. These findings support the need for a randomized trial to establish the role of HCQ in CVD prevention in RA patients.