Analysing Cord Blood Levels of TNF Inhibitors to Validate the EULAR Points to Consider for TNF Inhibitor Use During Pregnancy

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2021 Sep 8

PMID 34493490

Citations 7

Authors

Nafise Ghalandari

Erik Kemper

Ineke Hubertina Crijns

Gertjan Wolbink

Theo Rispens

Hieronymus Tw Smeele

Radboud Jem Dolhain

Affiliations

Soon will be listed here.

Abstract

Background: To minimise placental transfer of tumour necrosis factor inhibitors (TNFi), the European League Against Rheumatism (EULAR) created points to consider (PtC) for the use of TNFi during pregnancy. We are the first to validate the EULAR-PtC by analysing TNFi concentrations in cord blood.

Methods: Patients were derived from the Preconceptional Counselling in Active Rheumatoid Arthritis Study. TNFi was stopped at the time points recommended by the EULAR. Maternal blood and cord blood were collected and analysed for the concentration of TNFi.

Results: 111 patients were eligible for the analysis. Median stop time points were gestational age (GA) 37.0 weeks for certolizumab pegol, GA 25.0 weeks for etanercept, GA 19.0 weeks for adalimumab and GA 18.4 weeks for infliximab. Certolizumab pegol (n=68) was detectable in 5.9% of cord blood samples, with a median concentration of 0.3 µg/mL (IQR: 0.2-1.3) and a median cord/maternal concentration ratio of 0.010. Etanercept (n=30) was not detected in any cord blood samples. Adalimumab (n=25) was detectable in 48.0% of cord blood samples, with a median concentration of 0.5 µg/mL (IQR: 0.2-0.7) and a median concentration ratio of 0.062 (IQR: 0.018-0.15). Infliximab (n=14) was detectable in 57.1% of cord blood samples, with a median concentration of 0.4 µg/mL (IQR: 0.1-1.2) and a median concentration ratio of 0.012 (IQR: 0.006-0.081).

Conclusion: Compliance with the EULAR-PtC results in absence or low levels of TNFi in cord blood.

Citing Articles

Management of Rheumatic Diseases During Pregnancy and Breastfeeding: Position Paper of the Working Group for Obstetrics and Prenatal Medicine in the German Society for Gynecology and Obstetrics e. V. (AGG - Section Maternal Diseases in Pregnancy).

Kuschel B, Schafer-Graf U, Schmidt M, Kuhnert M, Hagenbeck C, Thurmel K Geburtshilfe Frauenheilkd. 2024; 84(2):130-143.

PMID: 38344044 PMC: 10853030. DOI: 10.1055/a-2201-2680.

Physiologic Changes During Pregnancy and Impact on Small-Molecule Drugs, Biologic (Monoclonal Antibody) Disposition, and Response.

Eke A, Gebreyohannes R, Fernandes M, Pillai V J Clin Pharmacol. 2023; 63 Suppl 1:S34-S50.

PMID: 37317492 PMC: 10365893. DOI: 10.1002/jcph.2227.

Reported congenital malformations after exposure to non-tumour necrosis factor inhibitor biologics: A retrospective comparative study in EudraVigilance.

Ghalandari N, Crijns H, Bergman J, Dolhain R, van Puijenbroek E, Hazes J Br J Clin Pharmacol. 2022; 88(12):5378-5388.

PMID: 35894810 DOI: 10.1111/bcp.15471.

Pharmacovigilance pregnancy data in a large population of patients with chronic inflammatory disease exposed to certolizumab pegol.

Clowse M, Fischer-Betz R, Nelson-Piercy C, Scheuerle A, Stephan B, Dubinsky M Ther Adv Musculoskelet Dis. 2022; 14:1759720X221087650.

PMID: 35464812 PMC: 9023886. DOI: 10.1177/1759720X221087650.

Continuous Use of Etanercept During Pregnancy Does Not Affect TNF-Alpha Levels in Umbilical Cord Blood.

Nishide M, Yagita M, Kumanogoh A Biologics. 2022; 16:17-19.

PMID: 35386275 PMC: 8979416. DOI: 10.2147/BTT.S358449.

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