Duke University Medical Center, Durham, North Carolina.
University of Texas Southwestern Medical Center, Dallas.
Arthritis Rheumatol. 2018 Sep;70(9):1399-1407. doi: 10.1002/art.40508. Epub 2018 Jul 22.
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.
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.
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.
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.
抗肿瘤坏死因子（anti-TNF）药物在控制慢性炎症性疾病方面具有显著疗效，但关于其在妊娠期间使用和安全性的数据较为有限。因此，anti-TNF 药物通常在妊娠早期被停用。培塞利珠单抗（CZP）是一种聚乙二醇化、无 Fc 段的 anti-TNF 药物，已获批用于治疗风湿性疾病和/或克罗恩病，其在胎盘内的主动转运极少或无。本分析旨在评估接受 CZP 治疗的女性的妊娠结局，尤其是妊娠早期暴露于 CZP 的女性。
通过 2017 年 3 月 6 日，从 UCB 制药安全数据库中提取关于母体 CZP 暴露的前瞻性和回顾性数据。分析仅限于前瞻性报告，以避免因回顾性提交而产生的潜在偏倚。确定活产数、流产数、选择性流产数、死胎数和主要先天畸形数。
在 1137 例前瞻性报告的妊娠中，母体暴露于 CZP，528 例（包括 10 例双胞胎妊娠）有 538 个已知结局：459 例活产（85.3%），47 例流产（8.7%），27 例选择性流产（5.0%），5 例死胎（0.9%）。459 例婴儿中，有 8 例（1.7%）患有主要先天畸形。452 例妊娠中有 367 例（81.2%）在第一孕期发生暴露，产生 459 例活产。在 452 例妊娠中有 201 例（44.5%）发生了整个孕期暴露。
本分析代表了最大的一组接受 anti-TNF 药物治疗慢性炎症性疾病的妊娠女性队列。与一般人群相比，妊娠结局分析并未表明 CZP 有致畸作用，也未增加胎儿死亡风险。对于考虑接受 CZP 治疗的育龄女性来说，这些数据令人放心。
