Department of Gastroenterology, St Vincent's Hospital Melbourne Pty Ltd, Melbourne, Australia.
University of Melbourne, Melbourne, Australia.
Aliment Pharmacol Ther. 2022 Mar;55(6):700-704. doi: 10.1111/apt.16739. Epub 2021 Dec 14.
Ustekinumab is increasingly used in pregnant women with inflammatory bowel disease (IBD). Existing safety data are reassuring, but the stability of ustekinumab levels in pregnancy, degree of transfer to the infant and time to infant clearance are unknown.
In this prospective observational study, ustekinumab-exposed women with IBD had trough levels measured in each trimester of pregnancy and at delivery. Infant ustekinumab levels were measured at delivery and ongoing until clearance was achieved. Trough ustekinumab level stability in individuals across pregnancy was compared by Skillings-Mack test. Spearman coefficients were used to correlate maternal and infant delivery levels, and median time to infant ustekinumab clearance was defined.
19 pregnant women receiving ustekinumab were included. There was no difference in ustekinumab levels across pregnancy in those with two or more representative trough levels (P = 0.83, n = 11). Infant delivery ustekinumab levels were higher than maternal levels, with a median infant:maternal ratio of 1.79 (IQR 1.26-3.1). There was a positive correlation between maternal and infant delivery ustekinumab levels (r = 0.75, P = 0.001) and an inverse correlation between the number of days from final antenatal dose and delivery infant ustekinumab level (r = -0.65, P = 0.006). Median time of infant ustekinumab clearance was 9 (range 6-19) weeks (n = 9).
Ustekinumab drug levels appear stable in pregnancy, with a delivery infant:maternal ratio similar to that of anti-TNFs. Infant ustekinumab clearance was complete by 20 weeks post-partum, however, infants exposed in utero should avoid live vaccination before 12 months of age until further clearance data are obtained.
越来越多的炎症性肠病（IBD）孕妇使用乌司奴单抗。现有的安全性数据令人安心，但乌司奴单抗在妊娠期间的稳定性、向婴儿的转移程度以及婴儿清除的时间尚不清楚。
在这项前瞻性观察研究中，IBD 接受乌司奴单抗治疗的孕妇在每个妊娠期间和分娩时测量药物谷浓度。在分娩时以及持续到清除为止，测量婴儿的乌司奴单抗水平。通过 Skillings-Mack 检验比较个体在整个妊娠期间的乌司奴单抗谷浓度稳定性。使用 Spearman 系数来关联母婴分娩时的水平，并定义婴儿清除乌司奴单抗的中位时间。
共纳入 19 名接受乌司奴单抗治疗的孕妇。在具有两个或更多代表性谷浓度的患者中，乌司奴单抗水平在整个妊娠期间没有差异（P=0.83，n=11）。婴儿分娩时的乌司奴单抗水平高于母体水平，中位数婴儿：母体比值为 1.79（IQR 1.26-3.1）。母婴分娩时的乌司奴单抗水平之间存在正相关（r=0.75，P=0.001），而从最后一次产前剂量到分娩时婴儿乌司奴单抗水平的天数之间存在负相关（r=-0.65，P=0.006）。婴儿乌司奴单抗清除的中位时间为 9 周（范围 6-19 周）（n=9）。
乌司奴单抗在妊娠期间药物水平似乎稳定，其婴儿：母体比值与抗 TNFs 相似。婴儿乌司奴单抗在产后 20 周内完全清除，但在获得进一步清除数据之前，在子宫内暴露的婴儿应在 12 个月前避免接种活疫苗。
