Safety Prediction of Infants Born to Mothers with Crohn's Disease Treated with Biological Agents in the Late Gestation Period

Abstract

Objectives: Knowledge gaps exist in the use of biologics for pregnant patients with Crohn's disease (CD), especially the usage of ustekinumab (UST) and infliximab (IFX) infusion during the late gestation period. In this case series, we investigated perinatal and neonatal outcomes and pharmacokinetics of these biologics in pregnant CD patients. Methods: Pregnant CD patients under treatment with IFX or UST during January 2017 to December 2019 were monitored. Growth and development of their babies were followed up to six months. Drug concentrations were measured in maternal peripheral and cord blood at delivery and infants' blood at six months of age. Results: Four cases were kept IFX treatment until late gestation (median last dose: 31.2 weeks). One case received UST until 23 weeks of gestation. All cases were in clinical remission but moderately undernourished. Babies were delivered by cesarean section at full term without any complications or congenital abnormalities. No growth or developmental defects and no susceptibility to infections were observed by six months. However, two babies whose mothers received IFX after 30 weeks of gestation were detected IFX in their blood at six months of age (0.94 and 0.24 pg/ml). Concentrations of UST in maternal and cord blood were 267.7 and 756.5 ng/ml, respectively. UST was not detected in the infant at six months of age. Conclusions: Administration of UST or IFX to pregnant patients with CD is safe, particularly IFX to be given in the late gestation period. Understanding of the pharmacokinetics of biologics in maternal-infant interactions may improve the management of pregnant CD patients.

What Should We Know about Drugs Levels and Therapeutic Drug Monitoring during Pregnancy and Breastfeeding in Inflammatory Bowel Disease under Biologic Therapy?

“…Data in the literature on ustekinumab pharmacokinetics during pregnancy remains unclear, limited to small case series and concern exclusively drug measurement in maternal, cord and infant blood and not on drug concentrations in intestinal tissues. Sako M et al investigated drug concentrations at delivery in maternal peripheral and cord blood from a patient with CD treated with ustekinumab and in infants' blood at six months (37). Similar to anti-TNF agents, the level of ustekinumab in cord blood was 2.8-fold higher compared with that measured in maternal serum, but drug concentration was undetectable in the baby's bloodstream after six months (37) (38) (39).…”

The Effect of Pregnancy and Inflammatory Bowel Disease on the Pharmacokinetics of Drugs Related to Inflammatory Bowel Disease—A Systematic Literature Review

“…A total of 12 studies [13][14][15][16][17][18][19][20][21][22][23][24] were included, of which four studies [14,15,17,21] presented data on more than one drug. Five unique drug types were found, namely infliximab (IFX), adalimumab (ADL), vedolizumab (VDZ), ustekinumab (UST) and golimumab (GLM).…”

“…In participants were included, of which 94% were diagnosed with CD and 6% with study of Mitrova et al [24] was a prospective cohort study in which the median 28 years. The study of Sako et al was a case report in which the woman was 35 age [22]. Both studies presented their data as unspecified concentration, only at d Since the concentration was only available at delivery, it was not possible to behavior of the UST concentration during the pregnancy.…”

“…The study of Mitrova et al [24] was a prospective cohort study in which the median age was 28 years. The study of Sako et al was a case report in which the woman was 35 years of age [22]. Both studies presented their data as unspecified concentration, only at delivery.…”

“…In conclusion, 12 studies were found that presented drug concentrations for IFX, ADL, VDZ, UST and GLM. Most studies [16,19,20,[22][23][24] only presented a concentration at delivery. The studies that presented data during the whole pregnancy showed an increase in concentration for IFX, a relative stable concentration for ADL and a decreasing concentration for VDZ.…”