Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Hunter Medical Research Institute, Kookaburra Circuit, Australia.
Clinical Pharmacology, Department of Medicine, The Royal Children's Hospital Melbourne, Australia.
J Crohns Colitis. 2022 Dec 5;16(12):1835-1844. doi: 10.1093/ecco-jcc/jjac093.
For infants exposed in utero to anti-tumour necrosis factor-α [TNF] medications, it is advised that live-attenuated vaccinations be postponed until the drug is cleared, but little is known about time to clearance. To minimize delays before live-attenuated vaccination can be given, we aimed to develop a pharmacokinetic model to predict time-to-clearance in infants exposed during pregnancy.
We prospectively followed in utero infliximab/adalimumab-exposed infants of mothers with inflammatory bowel disease across four countries between 2011 and 2018. Infants with a detectable anti-TNF umbilical-cord level and at least one other blood sample during the first year of life were included.
Overall, 107 infants were enrolled, including 166 blood samples from 71 infliximab-exposed infants and 77 samples from 36 adalimumab-exposed infants. Anti-TNF was detectable in 23% [n = 25] of infants at 6 months. At 12 months, adalimumab was not detected but 4% [n = 3] had detectable infliximab. A Bayesian forecasting method was developed using a one-compartment pharmacokinetic model. Model validation showed that the predicted clearing time was in accordance with the measured observations. A clinician-friendly online calculator was developed for calculating full anti-TNF clearing time: https://xiaozhu.shinyapps.io/antiTNFcalculator2/.
Almost one-quarter of infants born to mothers receiving anti-TNF during pregnancy have detectable anti-TNF at 6 months. To limit the time to live-attenuated vaccination in infants of mothers receiving anti-TNF during pregnancy, the results of a cord drug level at birth and a second sample ≥ 1 month thereafter can be used to estimate the time for full anti-TNF clearance in these children.
对于在子宫内接触过抗肿瘤坏死因子-α（TNF）药物的婴儿，建议在药物清除后再接种减毒活疫苗，但对于药物清除时间知之甚少。为了尽量减少在可以接种减毒活疫苗之前的延迟，我们旨在开发一种药代动力学模型来预测在子宫内暴露于妊娠期间的婴儿的清除时间。
我们在 2011 年至 2018 年期间在四个国家前瞻性地随访了患有炎症性肠病的母亲所生的在子宫内接受英夫利昔单抗/阿达木单抗的婴儿。纳入了脐带血中存在可检测的抗 TNF 水平且在生命的第一年至少有一个其他血液样本的婴儿。
总体而言，共纳入 107 名婴儿，包括 71 名接受英夫利昔单抗暴露的婴儿的 166 个血液样本和 36 名接受阿达木单抗暴露的婴儿的 77 个样本。在 6 个月时，23%[n=25]的婴儿可检测到抗 TNF。在 12 个月时，未检测到阿达木单抗，但有 4%[n=3]的婴儿可检测到英夫利昔单抗。使用单室药代动力学模型开发了贝叶斯预测方法。模型验证表明，预测的清除时间与测量的观察结果相符。开发了一个便于临床医生使用的在线计算器，用于计算全抗 TNF 清除时间：https://xiaozhu.shinyapps.io/antiTNFcalculator2/。
母亲在怀孕期间接受抗 TNF 治疗的婴儿中，近四分之一在出生后 6 个月时可检测到抗 TNF。为了限制在母亲怀孕期间接受抗 TNF 治疗的婴儿中进行减毒活疫苗接种的时间，可以使用出生时脐带药物水平和此后≥1 个月的第二个样本来估计这些儿童全抗 TNF 清除的时间。
