Pregnancy Outcomes After Exposure to Certolizumab Pegol Updated Results From a Pharmacovigilance Safety Database
Pregnancy Outcomes After Exposure to Certolizumab Pegol Updated Results From a Pharmacovigilance Safety Database
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DOI：
10.1002/art.40508
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发表时间：
2018-09-01
影响因子：
13.3
通讯作者：
Foerger, Frauke
中科院分区：
文献类型：
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作者：
Clowse, Megan E. B.;Scheuerle, Angela E.;Foerger, Frauke
目标。抗肿瘤坏死因子(抗肿瘤坏死因子)药物在控制慢性炎症性疾病方面是有效的，但关于它们在怀孕期间的使用和安全性的信息有限。因此，抗肿瘤坏死因子药物通常在怀孕早期停止使用。Certolizumab pegol(CZP)是一种聚乙二醇化的、不含FC的抗肿瘤坏死因子药物，被批准用于治疗风湿性疾病和/或克罗恩病，几乎没有活跃的胎盘转移。这项分析被用来评估服用CZP的妇女的妊娠结局，特别是那些在怀孕早期暴露的妇女。从UCB Pharma安全数据库中提取了截至2017年3月6日的孕妇CZP暴露的前瞻性和回溯性数据。分析仅限于前瞻性报告，以避免与回溯性提交相关的潜在偏见。确定活产、流产、择期流产、死产、重大先天畸形的发生情况。在1137例孕妇暴露于CZP的预期怀孕中，528例(包括10例双胞胎妊娠)有538例已知结局：459例活产(85.3%)，47例流产(8.7%)，27例选择性流产(5.0%)，5例死产(0.9%)。459例婴儿中有8例(1.7%)有严重的先天畸形。在452例妊娠中，有367例(81.2%)发生了早期妊娠暴露，导致459例活产。在452例孕妇中，201例(44.5%)在所有3个三个月期间暴露于空气中。这项分析代表了接受抗肿瘤坏死因子制剂治疗慢性炎症性疾病的孕妇的最大队列。对妊娠结局的分析表明，与普通人群相比，CZP没有致畸作用，也没有增加胎儿死亡的风险。这些数据对于考虑使用CZP治疗的育龄妇女来说是令人放心的。
Objective. Anti-tumor necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.Methods. Prospective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.Results. Of 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.Conclusion. This analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.