Despite the pivotal role that hydroxychloroquine (HCQ) plays in treating systemic lupus erythematosus (SLE), less than 50% of patients take HCQ as prescribed. Measurement of HCQ blood levels can help clinicians distinguish nonadherence versus lack of efficacy of HCQ. Our objective was to systematically review publications and perform a meta-analysis to examine the correlation between HCQ levels and 1) nonadherence and 2) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, in SLE.

A comprehensive search was performed. We included observational and interventional studies that measured HCQ levels and assessed adherence or SLEDAI scores in adults with SLE. Forest plots compared pooled estimates of correlations between HCQ levels and reported nonadherence or SLEDAI scores.

Among 604 studies screened, 17 were reviewed. We found 3-times higher odds of reported nonadherence in patients with low HCQ levels (odds ratio 2.95 [95% confidence interval (95% CI) 1.63, 5.35], P < 0.001). The mean SLEDAI score was 3.14 points higher in groups with below-threshold HCQ levels on a priori analysis (δ = 3.14 [95% CI -0.05, 6.23], P = 0.053), and 1.4 points higher in groups with HCQ levels of <500 ng/ml (δ = 1.42 [95% CI 0.07, 2.76], P = 0.039). Among 1,223 patients, those with HCQ levels ≥750 ng/ml had a 58% lower risk of active disease, and their SLEDAI score was 3.2 points lower.

We found a strong association between low HCQ levels and reported nonadherence. Our results suggest that HCQ levels of ≥750 ng/ml might be a potential therapeutic target.