Timing of Live Attenuated Vaccination in Infants Exposed to Infliximab or Adalimumab in Utero: A Prospective Cohort Study in 107 Children

• Published in: Journal of Crohn's and colitis Vol. 16; no. 12; pp. 1835 - 1844
• Main Authors: Liu, Zheng, Julsgaard, Mette, Zhu, Xiao, Martin, Jennifer, Barclay, Murray L, Cranswick, Noel, Gibson, Peter R, Gearry, Richard B, van der Giessen, Janine, Connor, Susan J, Rosella, Ourania, Grosen, Anne, Toong, Catherine, Flanagan, Emma, Wieringa, Jantien W, Janneke van der Woude, C, Bell, Sally J
• Format: Journal Article
• Language: English
• Published: England 05.12.2022
• Subjects: Adalimumab - therapeutic use; Bayes Theorem; Child; Female; Humans; Infant; Infant, Newborn; Inflammatory Bowel Diseases - drug therapy; Infliximab - therapeutic use; Maternal Exposure; Pregnancy; Prospective Studies; Tumor Necrosis Factor Inhibitors - therapeutic use; Vaccination; Vaccines, Attenuated - administration & dosage; pharmacokinetics; clearance; Anti-tumour necrosis factor alpha; pregnancy outcome; inflammatory bowel disease; pregnancy
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjac093

For infants exposed in utero to anti-tumour necrosis factor-α [TNF] medications, it is advised that live-attenuated vaccinations be postponed until the drug is cleared, but little is known about time to clearance. To minimize delays before live-attenuated vaccination can be given, we aimed to develop a pharmacokinetic model to predict time-to-clearance in infants exposed during pregnancy. We prospectively followed in utero infliximab/adalimumab-exposed infants of mothers with inflammatory bowel disease across four countries between 2011 and 2018. Infants with a detectable anti-TNF umbilical-cord level and at least one other blood sample during the first year of life were included. Overall, 107 infants were enrolled, including 166 blood samples from 71 infliximab-exposed infants and 77 samples from 36 adalimumab-exposed infants. Anti-TNF was detectable in 23% [n = 25] of infants at 6 months. At 12 months, adalimumab was not detected but 4% [n = 3] had detectable infliximab. A Bayesian forecasting method was developed using a one-compartment pharmacokinetic model. Model validation showed that the predicted clearing time was in accordance with the measured observations. A clinician-friendly online calculator was developed for calculating full anti-TNF clearing time: https://xiaozhu.shinyapps.io/antiTNFcalculator2/. Almost one-quarter of infants born to mothers receiving anti-TNF during pregnancy have detectable anti-TNF at 6 months. To limit the time to live-attenuated vaccination in infants of mothers receiving anti-TNF during pregnancy, the results of a cord drug level at birth and a second sample ≥ 1 month thereafter can be used to estimate the time for full anti-TNF clearance in these children.