Timing of Live Attenuated Vaccination in Infants Exposed to Infliximab or Adalimumab in Utero: A Prospective Cohort Study in 107 Children. (2nd July 2022)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of Crohn's and colitis. Volume 16:Number 12(2022)
• Page Start: 1835
• Page End: 1844
• Publication Date: 2022-07-02
• Subjects: Anti-tumour necrosis factor alpha -- clearance -- inflammatory bowel disease -- pharmacokinetics -- pregnancy -- pregnancy outcome; Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjac093
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background and Aims: 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. Methods: 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. Results: 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/ . Conclusions: 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. Graphical Abstract: