University of Wisconsin School of Medicine and Public Health, Madison.
AP-HP, Cochin University Hospital and Université de Paris, CRESS, INSERM, INRA, F-75004, Paris, France.
Arthritis Care Res (Hoboken). 2021 May;73(5):707-716. doi: 10.1002/acr.24155. Epub 2021 Mar 30.
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.
尽管羟氯喹（HCQ）在治疗系统性红斑狼疮（SLE）中起着关键作用，但只有不到 50%的患者按照规定服用 HCQ。测量 HCQ 的血药浓度可以帮助临床医生区分不依从与 HCQ 疗效不佳。我们的目的是系统地回顾文献并进行荟萃分析，以检查 HCQ 水平与 1）不依从和 2）SLE 疾病活动指数（SLEDAI）评分之间的相关性，在 SLE 中。
进行了全面的搜索。我们纳入了测量 HCQ 水平并评估成年人 SLE 中依从性或 SLEDAI 评分的观察性和干预性研究。森林图比较了 HCQ 水平与报告的不依从或 SLEDAI 评分之间相关性的汇总估计值。
在筛选的 604 项研究中，有 17 项进行了审查。我们发现，HCQ 水平较低的患者报告不依从的可能性高 3 倍（优势比 2.95 [95%置信区间（95%CI）1.63, 5.35]，P < 0.001）。预先分析显示，HCQ 水平低于阈值的组的平均 SLEDAI 评分高 3.14 分（δ = 3.14 [95%CI -0.05, 6.23]，P = 0.053），HCQ 水平<500 ng/ml 的组高 1.4 分（δ = 1.42 [95%CI 0.07, 2.76]，P = 0.039）。在 1223 名患者中，HCQ 水平≥750 ng/ml 的患者发生活动性疾病的风险降低 58%，其 SLEDAI 评分降低 3.2 分。
我们发现 HCQ 水平低与报告的不依从之间存在很强的关联。我们的结果表明，HCQ 水平≥750 ng/ml 可能是一个潜在的治疗目标。
