Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Department of Hygiene, Epidemiology, and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Autoimmun Rev. 2020 Apr;19(4):102491. doi: 10.1016/j.autrev.2020.102491. Epub 2020 Feb 19.
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.
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.
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.
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.
零星研究表明羟氯喹（HCQ）可能对原发性抗磷脂综合征（PAPS）患者的血栓预防有效，并可能导致抗磷脂抗体（aPL）滴度降低，但缺乏随机研究数据。
我们开展了一项试点、开放标签、前瞻性研究，旨在评估 HCQ 联合标准治疗（全身抗凝和/或抗血小板治疗）与单纯标准治疗相比，用于预防 50 例 PAPS 患者血栓形成的安全性和有效性，并评估 HCQ 对 50 例 PAPS 患者和 15 例无症状 aPL 携带者的 aPL 滴度的影响。
在平均 2.6 年的随访中，HCQ 联合标准治疗组的血栓发生率低于单纯标准治疗组（0.001 比 0.007，对数秩检验 p=0.048），调整年龄、性别、传统心血管危险因素、三重 aPL 阳性、基线时复发性血栓事件史和抗凝质量差（INR 水平在治疗范围内的时间≤80%）的影响后，多变量风险比为 0.09（95%CI=0.01-1.26，p=0.074）。两组间安全性结局无显著差异。除 IgM 抗心磷脂抗体外，长期使用 HCQ 与 aPL 滴度降低相关，且无论治疗分配如何，aPL 滴度随时间呈下降趋势。需要更大规模的随机试验来证实这一发现，并研究 HCQ 在无症状 aPL 携带者中的血栓保护作用。
