Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5 years of post-marketing experience
Pregnancy outcomes in patients with multiple sclerosis treated with teriflunomide: Clinical study data and 5 years of post-marketing experience
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DOI：
10.1177/1352458519843055
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发表时间：
2020-06-01
影响因子：
5.8
通讯作者：
Chambers, Christina
中科院分区：
文献类型：
--
作者：
Vukusic, Sandra;Coyle, Patricia K.;Chambers, Christina
背景：特立氟胺在怀孕期间是禁忌的。尽管指导人们采取有效的避孕措施，但仍有一些人怀孕了。目的：报告特立氟胺临床试验和上市后环境中发生的妊娠结果。方法：总结特立氟胺单药治疗临床试验和上市后的妊娠结果（数据截止日期：2017 年 12 月）。结果：在 437 例经确认的特立氟胺暴露妊娠中，222 例具有已知结果（70 例来自临床试验；152 例来自上市后环境）；前瞻性报告 161 项，回顾性报告 61 项。活产 107 例（48.2%），选择性流产 63 例（28.4%），自然流产 47 例（21.2%），宫外孕 3 例（1.4%），死产 1 例（0.5%），孕产妇死亡导致胎儿死亡 1 例（0.5%）。在已知妊娠结局的病例中报告了四种出生缺陷：输尿管肾盂扩张（仅被认为是严重缺陷）；先天性脑积水；室间隔缺损；以及右足外翻畸形。产前超声检查发现一例囊性水瘤（妊娠结局未知）。一项选择性流产是在产前诊断出胎儿异常（卵子枯萎）后进行的。临床试验中前瞻性报告的活产/死产结局中重大出生缺陷的风险为 3.6% (1/28)，上市后报告中为 0.0% (0/51)。结论：结果与一般人群一致。目前的人类数据并未表明接触特立氟胺的妊娠有致畸信号。
Background: Teriflunomide is contraindicated in pregnancy. Some pregnancies have occurred despite guidance to use effective contraception. Objectives: To report outcomes of pregnancies occurring in teriflunomide clinical trials and the post-marketing setting. Methods: Outcomes are summarized for pregnancies in teriflunomide monotherapy clinical trials and the post-marketing setting (data cutoff: December 2017). Results: Of 437 confirmed teriflunomide-exposed pregnancies, 222 had known outcomes (70 from clinical trials; 152 from the post-marketing setting); 161 were reported prospectively and 61 retrospectively. There were 107 (48.2%) live births, 63 (28.4%) elective abortions, 47 (21.2%) spontaneous abortions, 3 (1.4%) ectopic pregnancies, 1 (0.5%) stillbirth, and 1 (0.5%) maternal death leading to fetal death. Four birth defects were reported among cases with known pregnancy outcome: ureteropyeloectasia (only defect considered major); congenital hydrocephalus; ventricular septal defect; and malformation of right foot valgus. A case of cystic hygroma was identified on antenatal ultrasound (pregnancy outcome unknown). One elective abortion followed prenatal diagnosis of fetal anomaly (blighted ovum). The risk of major birth defects in prospectively reported live birth/stillbirth outcomes was 3.6% (1/28) in clinical trials and 0.0% (0/51) in post-marketing reports. Conclusions: Outcomes were consistent with the general population. Current human data do not indicate a teratogenic signal in teriflunomide-exposed pregnancies.