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

Zheng Liu; Mette Julsgaard; Xiao Zhu; Jennifer Martin; Murray L Barclay; Noel Cranswick; Peter R Gibson; Richard B Gearry; Janine van der Giessen; Susan J Connor; Ourania Rosella; Anne Grosen; Catherine Toong; Emma Flanagan; Jantien W Wieringa; C Janneke van der Woude; Sally J Bell; CARINA Study Group

doi:10.1093/ecco-jcc/jjac093

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

J Crohns Colitis. 2022 Dec 5;16(12):1835-1844. doi: 10.1093/ecco-jcc/jjac093.

Authors

Zheng Liu^{1

2

3}, Mette Julsgaard^{4

5

6}, Xiao Zhu^{7

8}, Jennifer Martin¹, Murray L Barclay⁹, Noel Cranswick², Peter R Gibson¹⁰, Richard B Gearry¹¹, Janine van der Giessen¹², Susan J Connor^{13

14

15}, Ourania Rosella¹⁰, Anne Grosen⁴, Catherine Toong^{14

16}, Emma Flanagan⁶, Jantien W Wieringa^{17

18}, C Janneke van der Woude¹², Sally J Bell^{6

19}; CARINA Study Group

Collaborators

CARINA Study Group:
Shannon Kanis, Jan Fallingborg, Christian L Hvas, Lisbet A Christensen, William R Connell, Steven J Brown, Jens Kjeldsen, Signe Wildt, Lise Svenningsen, Miles P Sparrow, Alissa Walsh, Graham Radford-Smith, Ian C Lawrance, Jane M Andrews, Kathrine Ellard

Affiliations

¹ Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Hunter Medical Research Institute, Kookaburra Circuit, Australia.
² Clinical Pharmacology, Department of Medicine, The Royal Children's Hospital Melbourne, Australia.
³ Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
⁴ Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
⁵ Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁶ Department of Gastroenterology, St Vincent's Hospital, and University of Melbourne, Melbourne, Australia.
⁷ Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, China.
⁸ School of Pharmacy, University of Otago, Dunedin, New Zealand.
⁹ Departments of Gastroenterology & Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand.
¹⁰ Department of Gastroenterology, Alfred Hospital, and Monash University, Melbourne, VIC, Australia.
¹¹ Department of Medicine, University of Otago, Christchurch, New Zealand.
¹² Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
¹³ Department of Gastroenterology, Liverpool Hospital, Sydney.
¹⁴ South Western Sydney Clinical, University of NSW Sydney.
¹⁵ Ingham Institute of Applied Medical Research, Sydney, Australia.
¹⁶ Sydney South West Pathology Service, Liverpool Hospital, University of NSW, Sydney, Australia.
¹⁷ Department of Pediatrics, Haaglanden Medical Center, the Hague, The Netherlands.
¹⁸ Department of Pediatrics, Division of Paediatric Infectious Diseases and Immunology, Erasmus MC University Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.
¹⁹ Department of Gastroenterology, Monash Health, and School of Clinical Sciences Monash University, Melbourne, VIC, Australia.

PMID: 35779236
DOI: 10.1093/ecco-jcc/jjac093

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.

Keywords: Anti-tumour necrosis factor alpha; clearance; inflammatory bowel disease; pharmacokinetics; pregnancy; pregnancy outcome.

MeSH terms

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

Substances

Adalimumab
Infliximab
Tumor Necrosis Factor Inhibitors
Vaccines, Attenuated

Abstract

MeSH terms

Substances

Grants and funding