Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection

Julsgaard, Mette, Christensen, Lisbet A., Gibson, Peter R., Gearry, Richard B., Fallingborg, Jan, Hvas, Christian L., Bibby, Bo M., Uldbjerg, Niels, Connell, William R., Rosella, Ourania, Grosen, Anne, Brown, Steven J., Kjeldsen, Jens, Wildt, Signe, Svenningsen, Lise, Sparrow, Miles P., Walsh, Alissa, Connor, Susan J., Radford-Smith, Graham, Lawrance, Ian C., Andrews, Jane M., Ellard, Kathrine and Bell, Sally J. (2016) Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection. Gastroenterology, 151 1: 110-119. doi:10.1053/j.gastro.2016.04.002


Author Julsgaard, Mette
Christensen, Lisbet A.
Gibson, Peter R.
Gearry, Richard B.
Fallingborg, Jan
Hvas, Christian L.
Bibby, Bo M.
Uldbjerg, Niels
Connell, William R.
Rosella, Ourania
Grosen, Anne
Brown, Steven J.
Kjeldsen, Jens
Wildt, Signe
Svenningsen, Lise
Sparrow, Miles P.
Walsh, Alissa
Connor, Susan J.
Radford-Smith, Graham
Lawrance, Ian C.
Andrews, Jane M.
Ellard, Kathrine
Bell, Sally J.
Title Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection
Journal name Gastroenterology   Check publisher's open access policy
ISSN 0016-5085
1528-0012
Publication date 2016-07
Year available 2016
Sub-type Article (original research)
DOI 10.1053/j.gastro.2016.04.002
Open Access Status Not Open Access
Volume 151
Issue 1
Start page 110
End page 119
Total pages 10
Place of publication Maryland Heights, MO, United States
Publisher W. B. Saunders
Collection year 2017
Language eng
Formatted abstract
Background & Aims: Little is known about in utero exposure to and postnatal clearance of anti-tumor necrosis factor (anti-TNF) agents in neonates. We investigated the concentrations of adalimumab and infliximab in umbilical cord blood of newborns and rates of clearance after birth, and how these correlated with drug concentrations in mothers at birth and risk of infection during the first year of life.

Methods: We performed a prospective study of 80 pregnant women with inflammatory bowel diseases at tertiary hospitals in Denmark, Australia, and New Zealand from March 2012 through November 2014: 36 received adalimumab and 44 received infliximab; 39 received concomitant thiopurines during pregnancy. Data were collected from medical records on disease activity and treatment before, during, and after pregnancy. Concentrations of anti-TNF agents were measured in blood samples from women at delivery and in umbilical cords, and in infants for every 3 months until the drug was no longer detected.

Results: The time from last exposure to anti-TNF agent during pregnancy correlated inversely with the concentration of the drugs in the umbilical cord (adalimumab: r = -0.64, P = .0003; infliximab: r = -0.77, P < .0001) and in mothers at time of birth (adalimumab, r = -0.80; infliximab, r = -0.80; P < .0001 for both). The median ratio of infant: mother drug concentration at birth was 1.21 for adalimumab (95% confidence interval [CI], 0.94-1.49) and 1.97 for infliximab (95% CI, 1.50-2.43). The mean time to drug clearance in infants was 4.0 months for adalimumab (95% CI, 2.9-5.0) and 7.3 months for infliximab (95% CI, 6.2-8.3; P < .0001). Drugs were not detected in infants after 12 months of age. Bacterial infections developed in 4 infants (5%) and viral infections developed in 16 (20%), all with benign courses. The relative risk for infection was 2.7 in infants whose mothers received the combination of an anti-TNF agent and thiopurine, compared with anti-TNF monotherapy (95% CI, 1.09-6.78; P = .02).

Conclusions: In a prospective study of infants born to mothers who received anti-TNF agents during pregnancy, we detected the drugs until 12 months of age. There was an inverse correlation between the time from last exposure during pregnancy and drug concentration in the umbilical cord. Infliximab was cleared more slowly than adalimumab from the infants. The combination of an anti-TNF agent and thiopurine therapy during pregnancy increased the relative risk for infant infections almost 3-fold compared with anti-TNF monotherapy. Live vaccines therefore should be avoided for up to 1 year unless drug clearance is documented, and pregnant women should be educated on the risks of anti-TNF use.
Keyword ERA Study
Inflammatory Bowel Diseases
Safety
Vaccination
Adalimumab
Infliximab
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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