Monfared Niloufar, Gold Matthew, Carbery Isabel, Laube Robyn, Selinger Christian P
Leeds Gastroenterology Institute, Leeds Teaching Hospitals, Leeds LS9 7TF, UK.
J Clin Med. 2023 Dec 20;13(1):34. doi: 10.3390/jcm13010034.
Maintenance of remission during pregnancy is vital for women with inflammatory bowel disease (IBD). The antenatal safety of novel small molecules for IBD is yet to be ascertained. We aimed to describe the current evidence on reproductive data regarding small-molecule drugs. We performed a systematic review searching Embase Classic + Embase and Ovid MEDLINE for reproductive outcomes for tofacitinib, filgotinib, upadacitininb, and ozanimod. Additionally, we asked the manufacturers for available data on file regarding reproduction. We analysed data from 10 sources; six studies and four manufacturer reports were identified from our search. Significant malformation risks were reported for tofacitinib, filgotinib, upadacitininb, and ozanimod in animal studies. In 126 tofacitinib-exposed pregnancies, there were 55 live births with 2 congenital malformations and 1 serious infant infection, 14 terminations, 15 miscarriages, and 42 outcomes unknown. In 50 filgotinib-exposed pregnancies, there were 20 healthy babies, 1 congenital malformation, 9 terminations, 10 miscarriages, and 10 outcomes unknown. In 78 upadacitinib-exposed pregnancies, there were 30 healthy babies, 15 terminations, 15 miscarriages, and 18 outcomes unknown. In 60 ozanimod-exposed pregnancies, there were 31 live births with 1 congenital malformation, 1 case of intra-uterine growth restriction, 1 case of neonatal icterus, 13 terminations, 9 miscarriages, and 8 unknown outcomes. Animal data suggest significant risks of malformations for tofacitinib, filgotinib, upadacitininb, and ozanimod. Human data from clinical trials and real-world observations do not show concerning data so far, but these are very limited. Currently, alternative treatments should be used for IBD during pregnancy.
对于炎症性肠病（IBD）女性患者而言，孕期维持病情缓解至关重要。新型IBD小分子药物的产前安全性尚未确定。我们旨在描述关于小分子药物生殖数据的现有证据。我们进行了一项系统综述，在Embase Classic + Embase和Ovid MEDLINE中检索托法替布、非戈替尼、乌帕替尼和奥扎莫德的生殖结局。此外，我们向制造商索要了存档的有关生殖的可用数据。我们分析了来自10个来源的数据；从我们的检索中识别出6项研究和4份制造商报告。动物研究报告了托法替布、非戈替尼、乌帕替尼和奥扎莫德存在显著的致畸风险。在126例暴露于托法替布的妊娠中，有55例活产，其中2例先天性畸形和1例严重婴儿感染，14例终止妊娠，15例流产，42例结局未知。在50例暴露于非戈替尼的妊娠中，有20例健康婴儿，1例先天性畸形，9例终止妊娠，10例流产，10例结局未知。在78例暴露于乌帕替尼的妊娠中，有30例健康婴儿，15例终止妊娠，15例流产，18例结局未知。在60例暴露于奥扎莫德的妊娠中，有31例活产，其中1例先天性畸形，1例宫内生长受限，1例新生儿黄疸，13例终止妊娠，9例流产，8例结局未知。动物数据表明托法替布、非戈替尼、乌帕替尼和奥扎莫德存在显著的致畸风险。目前，来自临床试验和真实世界观察的人类数据尚未显示出令人担忧的数据，但这些数据非常有限。目前，孕期IBD应采用替代治疗。
