Thématique :
Originalité :
Solidité :
Très solide
Doit faire évoluer notre pratique :
Nom du veilleur :
Mme Charlotte FAFART
Coup de coeur :
  2016 Jul;151(1):110-9  
  doi : 10.1053/j.gastro.2016.04.002  
  Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection  
  Julsgaard M, Christensen LA, Gibson PR, Gearry RB, Fallingborg J, Hvas CL, Bibby BM, Uldbjerg N, Connell WR Rosella O, Grosen A, Brown SJ, Kjeldsen J, Wildt S, Svenningsen L, Sparrow MP, Walsh A, Connor SJ, Radford Smith G, Lawrance IC, Andrews JM, Ellard K, Bell SJ  

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.

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.

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).

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.

Question posée
Quelles sont les concentrations d’IFX et d’ADA chez les enfants nés de mères exposées aux anti-TNF pendant leur grossesse et existe-t-il un impact sur le risque d’infection chez les enfants ?
Question posée
Un taux résiduel d’anti-TNF peut s’observer chez le nourrisson jusqu’à 12 mois après la naissance. L’IFX s’élimine plus lentement que l’ADA. Un sur-risque d’infection (X3) s’observait plus particulièrement chez les enfants dont la mère était sous combothérapie anti-TNF/azathioprine pendant la grossesse comparativement à un anti-TNF seul.

Ces résultats sont très intéressants et devraient changer notre pratique clinique. En effet, une combothérapie doit être évitée en raison du sur-risque d’infection. L’administration de vaccins vivants atténués devrait être retardée à non pas 6 mois mais 12 mois après la naissance. Une information de la patiente mais également des gynécologues et pédiatres est fondamentale lorsque la mère est traitée par anti-TNF au cours de sa grossesse.