Johns Hopkins University School of Medicine, Baltimore, Maryland.
Arthritis Rheumatol. 2021 Jun;73(6):997-1004. doi: 10.1002/art.41621. Epub 2021 May 2.
Hydroxychloroquine (HCQ) has a primary role in the prophylaxis and treatment of systemic lupus erythematosus (SLE) and may be protective against thrombosis in SLE. Optimal weight-based dosing of HCQ is unknown. This study was undertaken to examine the usefulness of HCQ blood monitoring in predicting thrombosis risk in a longitudinal SLE cohort.
HCQ levels were serially quantified from EDTA whole blood by liquid chromatography-tandem mass spectrometry. The mean HCQ blood levels calculated prior to thrombosis or until the last visit were compared using t-tests between patients with and those without thrombosis. Pooled logistic regression was used to analyze the association between rates of thrombosis and HCQ blood level. Rate ratios (RRs) and 95% confidence intervals (95% CIs) were calculated.
In 739 patients with SLE, thrombosis occurred in 38 patients (5.1%). The mean ± SD HCQ blood level was lower in patients who developed thrombosis versus those who did not develop thrombosis (720 ± 489 ng/ml versus 935 ± 580 ng/ml; P = 0.025). Thrombosis rates were reduced by 13% for every 200-ng/ml increase in the most recent HCQ blood level (RR 0.87 [95% CI 0.78-0.98], P = 0.025) and by 13% for mean HCQ blood level (RR 0.87 [95% CI 0.76-1.00], P = 0.056). Thrombotic events were reduced by 69% in patients with mean HCQ blood levels ≥1,068 ng/ml versus those with levels <648 ng/ml (RR 0.31 [95% CI 0.11-0.86], P = 0.024). This remained significant after adjustment for confounders (RR 0.34 [95% CI 0.12-0.94], P = 0.037).
Low HCQ blood levels are associated with thrombotic events in SLE. Longitudinal measurement of HCQ levels may allow for personalized HCQ dosing strategies. Recommendations for empirical dose reduction may reduce or eliminate the benefits of HCQ in this high-risk population.
羟氯喹（HCQ）在系统性红斑狼疮（SLE）的预防和治疗中具有主要作用，并且可能对 SLE 中的血栓形成具有保护作用。HCQ 的最佳基于体重的剂量尚不清楚。本研究旨在通过对纵向 SLE 队列进行 HCQ 血液监测，来研究其在预测血栓形成风险中的作用。
通过液相色谱-串联质谱法，从 EDTA 全血中连续定量 HCQ 水平。使用 t 检验比较血栓形成前或最后一次就诊前平均 HCQ 血药浓度在发生血栓形成的患者和未发生血栓形成的患者之间的差异。使用汇总逻辑回归分析血栓形成率与 HCQ 血药浓度之间的关系。计算率比（RR）和 95%置信区间（95%CI）。
在 739 例 SLE 患者中，38 例（5.1%）发生血栓形成。与未发生血栓形成的患者相比，发生血栓形成的患者 HCQ 血药浓度更低（720±489ng/ml 比 935±580ng/ml；P=0.025）。最近一次 HCQ 血药浓度每增加 200ng/ml，血栓形成率降低 13%（RR0.87[95%CI0.78-0.98]，P=0.025）；平均 HCQ 血药浓度降低 13%（RR0.87[95%CI0.76-1.00]，P=0.056）。与 HCQ 平均血药浓度<648ng/ml 的患者相比，HCQ 平均血药浓度≥1068ng/ml 的患者血栓形成事件减少 69%（RR0.31[95%CI0.11-0.86]，P=0.024）。在调整混杂因素后，这一结果仍具有统计学意义（RR0.34[95%CI0.12-0.94]，P=0.037）。
低 HCQ 血药浓度与 SLE 中的血栓形成事件相关。HCQ 水平的纵向测量可能允许制定个体化的 HCQ 剂量策略。对经验性剂量降低的建议可能会降低或消除 HCQ 在这一高危人群中的获益。
