Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers
Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers
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DOI：
10.1016/j.jacc.2020.05.045
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发表时间：
2020-07-21
影响因子：
24
通讯作者：
Buyon, Jill P.
中科院分区：
文献类型：
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作者：
Izmirly, Peter;Kim, Mimi;Buyon, Jill P.
实验和临床证据支持巨噬细胞Toll样受体信号传导在母体抗SSA/Ro介导的先天性心脏传导阻滞（CHB）中的作用。羟氯喹（HCQ）是一种广泛用于狼疮（包括妊娠期间）的口服Toll样受体拮抗剂，评价其降低CHB历史复发率18%的疗效。方法采用Simon最优方法设计多中心、开放、单组、2阶段临床试验。招募了既往妊娠合并CHB的抗SSA/Ro阳性母亲（n = 19阶段1; n = 35阶段2）。患者在妊娠第10周结束前每天接受400 mg HCQ，并在整个妊娠期间维持该剂量。主要结局为妊娠期间任何时间的2度或3度CHB，次要结局包括孤立性内膜弹力纤维增生症、出生时的1度CHB和皮疹。结果：通过意向治疗（ITT）分析，54例可评估妊娠中有4例导致主要结局（7.4%; 90%置信区间：3.4%至15.9%）。由于9名母亲在入组后但在主要结局之前服用了潜在的混淆药物（氟化糖皮质激素和/或静脉注射免疫球蛋白），为了单独评价HCQ，招募了另外9名母亲并遵循相同的方案。在仅限于暴露于HCQ的妊娠的符合方案分析中，54例胎儿中有4例（7.4%）出现了与ITT相同的主要结局。次要结局包括轻度内膜弹力纤维增生症（n = 1）和皮肤新生儿狼疮（n = 4）。结论：这些前瞻性数据支持HCQ显著降低CHB的复发率，低于历史发生率> 50%，表明该药应用于抗SSA/Ro暴露妊娠的胎儿心脏病二级预防。（羟氯喹[PATCH]预防先天性心脏传导阻滞的方法;（c）美国心脏病学会基金会2020年。
BACKGROUND Experimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro-mediated congenital heart block (CHB). OBJECTIVES Hydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. METHODS This multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon's optimal approach. Anti-SSA/Ro-positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2 degrees or 3 degrees CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1 degrees CHB at birth and skin rash. RESULTS By intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). CONCLUSIONS These prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; (c) 2020 by the American College of Cardiology Foundation.