Adalimumab during pregnancy puts baby at risk during vaccination

A 34-year-old woman, who took adalimumab for Crohn’s disease during pregnancy, gave birth to a baby who continues to have the drug in its system for 19 months and counting.

The case serves as a warning that adalimumab and similar medications could persist far longer than expected in infants born to mothers treated for inflammatory bowel disease (IBD), noted the woman’s physicians at University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France, who reported the case in Annals of Internal Medicine.

Adalimumab is a recombinant monoclonal antibody that binds to tumor necrosis factor-alpha (TNF-α) and blocks its interaction with TNF receptors. TNF inhibitors, including adalimumab and infliximab, are immunosuppressive agents that can increase the risk of serious infections. Thus, live vaccines are contraindicated in patients until TNF inhibitors are cleared from the system.

“On the basis of our experience, we suggest that clinicians caring for infants whose mothers received these agents during pregnancy consider measuring antibody levels in the infant before administering live vaccines,” the physicians wrote. 

In their article, the authors cited another case in which a 4.5-month-old infant died of disseminated bacillus Calmette-Guérin (BCG) infection after receiving routine BCG vaccination. The infant’s mother had been treated with infliximab throughout her pregnancy for symptoms of Crohn’s disease.

Unexplained persistence

In this newer case, the 34-year-old patient was in the first trimester of pregnancy when she experienced a clinical relapse of Crohn’s disease. Her physicians increased her dose of adalimumab until the disease was controlled, and then continued the TNF inhibitor at a maintenance dose for the rest of her pregnancy.

The patient had an uneventful vaginal delivery at 39 weeks gestation, and breastfed the baby for 3 months. She continued the same dose of adalimumab and her Crohn’s disease has remained in remission.

Monoclonal antibodies are known to cross the placental barrier during pregnancy, with the largest amount transferred during the third trimester, such that fetal levels rise above maternal levels. Adalimumab has also been found at small doses in the breast milk of mothers treated with the drug.

“We have measured the infant’s adalimumab levels since birth,” the authors wrote. “Representative values include 0.57 μg/mL at 9 months, 1.66 μg/mL at 13 months, 2.90 μg/mL at 17 months, and 1.07 μg/mL at 19 months.”

Otherwise, the infant has been developing normally, they added.

“This case is remarkable because the infant had measurable levels of adalimumab much longer than in
previous reports,” the physicians noted. “The persistence of this agent remains unexplained, although others have suggested that delayed clearance of antibodies by immature endoplasmic reticulum may be the cause.”

Regardless of the cause, the researchers advised clinicians to be aware of this possibility and to delay vaccines in children born to mothers treated with TNF inhibitors for inflammatory bowel disease.