Ustekinumab during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk, and infant serum

Jumpei Saito; Kayoko Kaneko; Hiroyo Kawasaki; Takeshi Hayakawa; Naho Yakuwa; Tomo Suzuki; Haruhiko Sago; Akimasa Yamatani; Atsuko Murashima

doi:10.1186/s40780-022-00249-8

Ustekinumab during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk, and infant serum

J Pharm Health Care Sci. 2022 Jul 1;8(1):18. doi: 10.1186/s40780-022-00249-8.

Authors

Jumpei Saito¹, Kayoko Kaneko², Hiroyo Kawasaki³, Takeshi Hayakawa⁴, Naho Yakuwa⁵, Tomo Suzuki⁶, Haruhiko Sago⁶, Akimasa Yamatani³, Atsuko Murashima^{2

5}

Affiliations

¹ Department of Pharmacy, National Center for Child Health and Development, Okura 2-10-1, Setagaya-ku, Tokyo, 157-8535, Japan. saito-jn@ncchd.go.jp.
² Division of Maternal Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.
³ Department of Pharmacy, National Center for Child Health and Development, Okura 2-10-1, Setagaya-ku, Tokyo, 157-8535, Japan.
⁴ Sangenjaya Hayakawa Clinic, Tokyo, Japan.
⁵ Japan Drug Information Institute in Pregnancy, National Center for Child Health and Development, Tokyo, Japan.
⁶ Division of Obstetrics, Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan.

Abstract

Background: Patients with ulcerative colitis (UC) may be concerned about medication safety during preconception, pregnancy, and lactation, and they should be closely followed up to ensure that UC activity is controlled during the perinatal period. Reported information on the safety of ustekinumab during pregnancy and lactation is limited. In this case report, we examined the safety of ustekinumab in a fetus and breastfed infant with reference to drug concentrations in maternal serum, cord blood, breast milk, and infant serum.

Case presentation: A 36-year-old female who developed hematochezia and was diagnosed with ulcerative colitis at age 24 was pregnant with her first child. During pregnancy she was treated with subcutaneous bimonthly ustekinumab, at a dose of 90 mg, until 29 weeks of gestation. Her ulcerative colitis symptoms remained in remission. At 38 weeks of gestation she underwent cesarean section and delivered a healthy female infant weighing 3043 g and with no congenital malformations. The infant received routine vaccinations with no adverse events. Ustekinumab treatment was resumed at 7 weeks postpartum. The ustekinumab concentration in maternal serum at 12 days after injection (30.7 weeks of gestation) was 7968.5 ng/mL, and it decreased to 106.1 ng/mL at 114 days after the last dose. In cord blood, the ustekinumab concentration was 1131.2 ng/mL at 65 days after the last dose; this was 2.5 times higher than that in the maternal serum, which was consistent with a previous report. Ustekinumab was detected in infant serum collected at 71 days after the last maternal dose (299.0 ng/mL), with rapid elimination from the infant's body. In breast milk, the maximum ustekinumab concentrations were 13.6 ng/mL at 9 days after the last maternal dose, respectively. The ratio of the calculated areas under the time-concentration curves of ustekinumab in breast milk and maternal serum was 0.0008 (257.1/327632.7), which was comparable with a previous human study.

Conclusion: The placental transfer and breast milk secretion of ustekinumab in our case were comparable with previous reports. Use of ustekinumab during pregnancy and lactation was feasible in this case. Further research is needed to clarify the safety of ustekinumab during pregnancy and lactation.

Keywords: Lactation; Pregnancy; Ulcerative colitis; Ustekinumab.