Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
Department of Community Health Sciences, University of Calgary, Calgary, Canada.
Aliment Pharmacol Ther. 2017 May;45(10):1329-1338. doi: 10.1111/apt.14040. Epub 2017 Mar 20.
Transplacental transfer of infliximab and adalimumab results in detectable drug levels in the cord blood and infant.
To determine if pregnancy influenced the pharmacokinetics of anti-TNF agents in women with inflammatory bowel disease.
Twenty-five women from the University of Calgary inflammatory bowel disease(IBD) pregnancy clinic on maintenance infliximab or adalimumab were recruited prospectively with serum bio-banking performed each trimester. Infliximab trough and adalimumab steady-state levels were the outcomes of interest and were analysed using the ANSER infliximab and adalimumab assays. Multivariate linear mixed-effects models were constructed to assess infliximab and adalimumab drug levels during pregnancy adjusting for the clinical covariates of albumin, BMI and CRP.
Fifteen women (eight Crohn's disease, seven ulcerative colitis) received infliximab and 10 women with 11 pregnancies were treated with adalimumab. Median age was 29.6 years (IQR: 27.6-31.2 years). Median disease duration was 9.2 years (IQR: 3.16-15.0 years). Median trough infliximab concentrations were 8.50 μg/mL (IQR: 7.23-10.07 μg/mL), 10.31 μg/mL (IQR: 7.66-15.63 μg/mL) and 21.02 μg/mL (IQR: 16.01-26.70 μg/mL) at trimesters 1, 2 and 3 respectively. Significant changes in albumin and BMI (P < 0.05) but not CRP (P > 0.05) were documented throughout pregnancy. After adjusting for albumin, BMI and CRP, infliximab trough levels increased during pregnancy, by 4.2 μg/mL per trimester (P = 0.02), while adalimumab drug levels remained stable (P > 0.05).
Infliximab levels rise during pregnancy, whereas adalimumab levels remain stable after accounting for changes in albumin, BMI and CRP. Therapeutic drug monitoring in the second trimester may be useful in guiding dosing in the third trimester.
英夫利昔单抗和阿达木单抗经胎盘转运可使脐血和婴儿血中检测到药物水平。
确定妊娠是否影响炎症性肠病（IBD）妇女中抗 TNF 药物的药代动力学。
卡尔加里大学 IBD 妊娠诊所的 25 名接受英夫利昔单抗或阿达木单抗维持治疗的妇女前瞻性入组，并在每个孕早期进行血清生物样本库检测。英夫利昔单抗谷浓度和阿达木单抗稳态浓度是本研究的观察终点，并使用 ANSER 英夫利昔单抗和阿达木单抗检测进行分析。采用多元线性混合效应模型，根据白蛋白、BMI 和 CRP 的临床协变量，评估妊娠期间英夫利昔单抗和阿达木单抗的药物水平。
15 名妇女（8 名克罗恩病，7 名溃疡性结肠炎）接受英夫利昔单抗治疗，10 名妇女（11 名孕妇）接受阿达木单抗治疗。中位年龄为 29.6 岁（IQR：27.6-31.2 岁）。中位疾病病程为 9.2 年（IQR：3.16-15.0 年）。英夫利昔单抗谷浓度中位数分别为妊娠 1、2 和 3 期的 8.50μg/ml（IQR：7.23-10.07μg/ml）、10.31μg/ml（IQR：7.66-15.63μg/ml）和 21.02μg/ml（IQR：16.01-26.70μg/ml）。在整个妊娠期间，白蛋白和 BMI（P<0.05）发生了显著变化，但 CRP 没有（P>0.05）。在调整白蛋白、BMI 和 CRP 后，英夫利昔单抗谷浓度在妊娠期间每增加 4.2μg/ml（P=0.02），而阿达木单抗药物浓度保持稳定（P>0.05）。
英夫利昔单抗水平在妊娠期间升高，而阿达木单抗水平在考虑白蛋白、BMI 和 CRP 变化后保持稳定。在妊娠中期进行治疗药物监测可能有助于指导妊娠晚期的剂量调整。
