Analysing cord blood levels of TNF inhibitors to validate the EULAR points to consider for TNF inhibitor use during pregnancy

Ann Rheum Dis. 2022 Mar;81(3):402-405. doi: 10.1136/annrheumdis-2021-221036. Epub 2021 Sep 7.

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.

Keywords: arthritis; certolizumab pegol; etanercept; rheumatoid; tumor necrosis factor inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adalimumab / blood
  • Adult
  • Antirheumatic Agents
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Certolizumab Pegol / blood
  • Etanercept / blood
  • Female
  • Fetal Blood / chemistry*
  • Fetal Blood / drug effects
  • Gestational Age
  • Humans
  • Infliximab / blood
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / drug therapy*
  • Reference Values
  • Reproducibility of Results
  • Rheumatology / standards*
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / blood*

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor Inhibitors
  • Infliximab
  • Adalimumab
  • Etanercept
  • Certolizumab Pegol