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The Clinical Significance of Monitoring Hydroxychloroquine Levels in Patients with Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis


Garg S1, Unnithan R2, Hansen KE1, Costedoat-Chalumeau N3,4, Bartels CM1. Arthritis Care Res (Hoboken). 2020 Jan 31. doi: 10.1002/acr.24155. [Epub ahead of print]

Author Information

1 University of Wisconsin, School of Medicine and Public Health, Department of Medicine, Rheumatology Division, Madison, WI, US.

2 University of Wisconsin, School of Medicine and Public Health, Madison, WI.

3 AP-HP, Cochin University Hospital, Internal Medicine Department, Referral center for rare autoimmune and systemicdiseases, Paris, France.

4 Université de Paris, CRESS, INSERM, INRA, F-75004, Paris, France.



Despite the pivotal role that hydroxychloroquine (HCQ) plays in treating 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. We systematically reviewed publications and performed a meta-analysis to examine the correlation between HCQ levels and 1) nonadherence, and 2) SLEDAI scores, in SLE.


A comprehensive search was performed. We included observational and interventional studies that measured HCQ levels, and assessed adherence or SLEDAI 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 (OR 2.95, 95% CI 1.63, 5.35, p <0.001). The mean SLEDAI score was 3.14 points higher in group 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 group with HCQ levels below 500 ng/ml (δ = 1.42, 95% CI 0.07, 2.76, p=0.039). Among 1223 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 good association between low HCQ levels and reported nonadherence. Our results suggest that HCQ levels ≥750 ng/mL might be a potential therapeutic target.