Rheumatology Unit, Department of Medicine, University Hospital of Padua, Padua Italy.
Rheumatology Unit, Department of Medicine, University Hospital of Padua, Padua Italy.
Semin Arthritis Rheum. 2021 Feb;51(1):28-35. doi: 10.1016/j.semarthrit.2020.10.001. Epub 2020 Dec 17.
The most efficacious strategy to manage pregnant patients with antiphospholipid syndrome (APS) refractory to conventional heparin/low-dose aspirin treatment or at high risk of adverse pregnancy outcomes has not been determined with any degree of certainty. The study set out to evaluate the efficacy and safety of the second-line treatments most frequently used in addition to conventional therapy, and the data were analyzed to identify which is/are associated to the best pregnancy outcomes.
A systematic review of the literature on studies concerning second-line treatments for refractory and/or high risk pregnant APS women published between February 2006 and February 2020 was conducted. The records were retrieved by searching Medline via Pubmed, the Web of Science platform, the Cochrane library database and clinicaltrials.gov.
Fourteen studies met the eligibility criteria of the review: six retrospective cohort studies, one case-control, one case-series and six case reports. The results of single treatment protocols based upon hydroxychloroquine (HCQ), low-dose steroids (LDS), intravenous immunoglobulins (IVIG), plasma exchange (PE) or pravastatin and of combination protocols based upon HCQ+LDS, IVIG+LDS, PE+LDS and PE+IVIG used during 313 pregnancies in 303 APS women were analyzed and compared. The second-line treatments produced 261/313 (83.4%) live births; severe pregnancy complications were registered in 75/313 (24%) pregnancies. Drug side-effects were observed in 3/313 (0.9%) pregnancies. Statistical analysis identified a significantly higher live birth rate and/or a significantly lower number of severe complications in the pregnancies treated with IVIG, HCQ, pravastatin, PE+IVIG and PE+LDS.
Our results suggest using low-dose IVIG (< 2 g/Kg/month) or HCQ 400 mg/day starting before pregnancy in women with APS refractory to conventional therapy, while high-dose IVIG (2 g/Kg/month) associated with PE or alone in those with high risk±refractory APS.
对于常规肝素/低剂量阿司匹林治疗无效或有不良妊娠结局高风险的抗磷脂综合征（APS）孕妇，目前尚无法确定最有效的治疗策略。本研究旨在评估除常规治疗外最常使用的二线治疗的疗效和安全性，并对数据进行分析以确定哪种治疗方法与最佳妊娠结局相关。
对 2006 年 2 月至 2020 年 2 月期间发表的关于难治性和/或高危妊娠 APS 妇女二线治疗的文献进行了系统性回顾。通过 Medline 经 Pubmed、Web of Science 平台、Cochrane 图书馆数据库和 clinicaltrials.gov 检索文献。
共有 14 项研究符合本综述的纳入标准：6 项回顾性队列研究、1 项病例对照研究、1 项病例系列研究和 6 项病例报告。分析比较了羟氯喹（HCQ）、低剂量类固醇（LDS）、静脉注射免疫球蛋白（IVIG）、血浆置换（PE）或普伐他汀单一治疗方案，以及 HCQ+LDS、IVIG+LDS、PE+LDS 和 PE+IVIG 联合治疗方案，共 303 例 APS 妇女的 313 次妊娠。二线治疗产生 261/313（83.4%）活产；75/313（24%）妊娠中出现严重妊娠并发症。3/313（0.9%）妊娠中观察到药物副作用。统计分析显示，IVIG、HCQ、普伐他汀、PE+IVIG 和 PE+LDS 治疗的妊娠活产率更高，或严重并发症更少。
我们的结果表明，对于常规治疗无效的 APS 妇女，在怀孕前开始使用低剂量 IVIG（<2 g/Kg/月）或 HCQ 400mg/天，而对于高危+难治性 APS 妇女，使用高剂量 IVIG（2 g/Kg/月）联合 PE 或单独使用。
