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管理妊娠、哺乳期炎症性肠病的药理学方法:生物制剂和口服小分子治疗药物。

A Pharmacological Approach to Managing Inflammatory Bowel Disease During Conception, Pregnancy and Breastfeeding: Biologic and Oral Small Molecule Therapy.

机构信息

Inflammatory Bowel Disease Centre, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z1, Canada.

出版信息

Drugs. 2019 Jul;79(10):1053-1063. doi: 10.1007/s40265-019-01141-w.

Abstract

The inflammatory bowel diseases commonly affect individuals during their peak reproductive years. Patients are often concerned about the impact of medical therapies on their ability to conceive, effect on the fetus, as well as the ability to breastfeed, which has led to poor medical adherence during pregnancy. However, most medications are safe, and discontinuation may lead to active disease, which is associated with adverse materno-fetal outcomes. The anti-TNF biologic therapies, infliximab and adalimumab have been extensively studied in the context of pregnancy. They are actively transferred to the placenta during the second and third trimesters; these have not been associated with an increased rate of congenital abnormalities or fetal death. The minimal amounts of drug that are transferred to breast milk are proteolyzed by the infant's digestive system with no reported short- or long-term adverse effects. There is a paucity of clinical data for the other approved anti-TNF agents or newer anti-integrin (vedolizumab) and anti-interleukin (ustekinumab) therapies used in the management of inflammatory bowel disease; however, no significant safety signals have been documented thus far. The new oral small molecule therapy, tofacitinib is teratogenic in animal models and is contra-indicated in patients attempting pregnancy. It is important that patients, as well as physicians managing patients with these conditions, be aware of the impact of these medical therapies during pregnancy.

摘要

炎症性肠病通常在个体的生育高峰期发作。患者通常会担心医学治疗对其生育能力、对胎儿的影响以及哺乳能力的影响,这导致了怀孕期间医疗依从性差。然而,大多数药物是安全的,停药可能会导致疾病活动,这与母婴不良结局有关。抗 TNF 生物制剂英夫利昔单抗和阿达木单抗在妊娠背景下已得到广泛研究。它们在妊娠第二和第三阶段积极向胎盘转移;这些药物与先天畸形或胎儿死亡的发生率增加无关。转移到母乳中的药物量很少,会被婴儿的消化系统蛋白水解,没有报告短期或长期的不良影响。其他已批准的抗 TNF 药物或新型抗整合素(vedolizumab)和抗白细胞介素(ustekinumab)治疗炎症性肠病的药物的临床数据很少;然而,迄今为止尚未记录到明显的安全信号。新型口服小分子药物托法替布在动物模型中具有致畸性,在试图怀孕的患者中禁用。重要的是,患者以及管理这些疾病的医生都应该意识到这些医学治疗在怀孕期间的影响。

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