Despite implementation of the isotretinoin PPP in most member states, isotretinoin-exposed pregnancies were reported. This has led some member states to implement additional measures to the PPP, resulting in inconsistency with the approach agreed in 2003 following the European-wide review. It has been further suggested that common elements should be developed for PPPs for all medicines that are known to carry a high teratogenic risk.

BackgroundTo 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.MethodsPatients 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.Results111 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).ConclusionCompliance with the EULAR-PtC results in absence or low levels of TNFi in cord blood.

The observed non-adherence to the isotretinoin PPP calls for careful evaluation of risk minimisation plans and participation of all stakeholders in the development of these plans.

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