BACKGROUND Sporadic studies suggest hydroxychloroquine (HCQ) may be effective for thrombosis prevention in patients with primary antiphospholipid syndrome (PAPS) and may lead to antiphospholipid antibody (aPL) titer reduction but data from randomized studies are lacking. METHODS We conducted a pilot open-label randomized prospective study aiming to evaluate the safety and efficacy of HCQ for thrombosis prevention in 50 patients with PAPS allocated 1:1 to HCQ plus standard care (systemic anticoagulation and/or antiplatelet therapy) vs. standard care alone, as well as the effect of HCQ on aPL titers of 50 PAPS patients and 15 asymptomatic aPL carriers. RESULTS HCQ use plus standard care was associated with lower incidence rate of thrombosis than standard care alone (0.001 vs. 0.007, log-rank p =0.048) over an average 2.6-year follow-up, and a multivariate hazard ratio of 0.09 (95% CI = 0.01-1.26, p = 0.074) after adjusting for the effect of age, sex, traditional cardiovascular risk factors, triple aPL positivity, history of recurrent thrombotic events at baseline, and poor anticoagulation quality (INR levels within therapeutic range for ≤80% of follow-up). No significant difference in safety outcomes was observed between the two groups. Long-term HCQ use was associated with a decrease in aPL titers except for IgM anticardiolipin antibodies, which tended to decrease overtime regardless of treatment allocation. CONCLUSIONS HCQ may represent an effective adjuvant treatment for thrombosis prevention in patients with PAPS, which may be mediated via a reduction in aPL titers. Larger randomized trials are needed in order to corroborate this finding and investigate the thromboprotective role of HCQ in asymptomatic aPL carriers.

中文翻译：

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羟氯喹对原发性抗磷脂综合征中血栓形成的预防和抗磷脂抗体水平的影响：一项开放性试验性前瞻性随机前瞻性研究。

背景技术零星的研究表明，羟氯喹（HCQ）可以有效预防原发性抗磷脂综合征（PAPS）患者的血栓形成，并可能导致抗磷脂抗体（aPL）效价降低，但是缺乏随机研究的数据。方法我们进行了一项开放性试验性前瞻性随机前瞻性研究，旨在评估HCQ预防1：1分配给HCQ加标准治疗（全身抗凝和/或抗血小板治疗）与标准治疗的PAPS患者的安全性和有效性。以及HCQ对50名PAPS患者和15名无症状aPL携带者的aPL效价的影响。结果在平均2.6年的随访中，使用HCQ加标准护理与血栓形成的发生率比仅标准护理更低（0.001比0.007，对数秩p = 0.048），调整年龄，性别，传统心血管危险因素，三重aPL阳性，基线时血栓事件复发史和抗凝不良的影响后，多因素风险比为0.09（95％CI = 0.01-1.26，p = 0.074）。质量（INR水平在治疗范围内，≤随访的80％）。两组之间在安全性结果上没有观察到显着差异。长期使用HCQ会导致aPL滴度降低，但IgM抗心磷脂抗体却会随着治疗时间的延长而逐渐降低，而与治疗分配无关。结论HCQ可能是预防PAPS患者血栓形成的有效辅助治疗，这可以通过降低aPL滴度来介导。