POS0202 ANALYZING CORD BLOOD LEVELS OF TNF INHIBITORS TO VALIDATE THE EULAR POINTS-TO-CONSIDER FOR TNF INHIBITOR USE DURING PREGNANCY
Authors: E. Kemper, N. Ghalandari, H. J. M. J. Crijns, H. T. Smeele, R. Dolhain
Journal: Annals of the Rheumatic Diseases (2021)

Background: Increasing evidence suggests that TNF inhibitors (TNFi) are safe to use during pregnancy 1 . A drawback of TNFi use during pregnancy is active transport across the placenta, which is affected by the structure of the TNFi 1 . The European League Against Rheumatism (EULAR) defined points to consider (PtC) on the use of TNFi during pregnancy 2 : to prevent placental transfer, etanercept should be discontinued at gestational age (GA) 30-32 weeks, and both adalimumab and infliximab should be discontinued at GA 20 weeks. Certolizumab pegol can be conditionally continued throughout pregnancy. Objectives: The aim of this research is to validate the EULAR PtC by measuring the level of TNFi in cord blood. Methods: Patients were derived from the PreCARA study, an ongoing prospective cohort study on inflammatory rheumatic diseases and pregnancy in the Netherlands. Patients were treated according to a treat-to-target approach, which included the use of TNFi. TNFi were, if possible, discontinued at recommended stop time points. Maternal blood samples were collected in each trimester. Cord blood was analyzed for the presence of certolizumab pegol, etanercept, adalimumab and infliximab. Levels of TNFi in the cord blood were compared between patients that stopped at the advised GA and patients who did not. Results: Data from 111 patients with inflammatory rheumatic diseases were used for the current analysis. Most patients stopped treatment before the recommended GA (table 1). Certolizumab pegol (n = 68) was measured in a low number of cord blood samples (5.9%) and in low concentrations (median, (IQR): 0.25 µg/ml (0.15 – 1.3)). Etanercept was not detected in any cord blood samples (n = 28). Adalimumab (n = 24) and infliximab (n = 13) were measured more often in cord blood (in 50.0% and 61.5% of patients, respectively), this also was observed in patients that stopped before the recommended GA (in 47.7% for adalimumab and 60.0% for infliximab). However, the observed concentrations were low: the maximum observed concentrations in cord blood were 2.1 µg/ml (stopped at GA 19.4 weeks) for adalimumab and 4.5 µg/ml (stopped at GA 21.1 weeks) for infliximab. Conclusion: Stopping TNFi around the GA recommended by the EULAR PtC resulted in no measurable levels or low concentrations of TNF inhibitor in the cord blood in a majority of patients. References: [1]Smeele HTW, Dolhain RJEM. Current perspectives on fertility, pregnancy and childbirth in patients with Rheumatoid Arthritis. Semin Arthritis Rheum. 2019;49(3S):S32-S35. doi:10.1016/j.semarthrit.2019.09.010 [2]Götestam Skorpen C, Hoeltzenbein M, Tincani A, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis . 2016;75(5):795-810. doi:10.1136/annrheumdis-2015-208840 Table 1. TNF inhibitor use during pregnancy and TNF inhibitor concentrations in mother’s blood and cord blood. Certolizumab pegol (n = 68) Etanercept (n = 28) Adalimumab (n = 24) Infliximab (n = 13) Stop time point as recommended by EULAR N/A GA 30-32 GA 20 GA 20 Gestational age at time of stopping TNFi, median±IQR 37.29 (32.79 – 38.29) 25.43 (18.71 – 28.36) 18.79 (8.93 – 19.86) 18.86 (14.57 – 20.00) Measurable TNFi in cord blood, n (%) 4 (5.9%) 0 (0%) 12 (50.0%) 8 (61.5%) Maternal concentration of TNFi in the 1st trimester, median±IQR (µg/ml) 24.55 (19 – 31) 2.1 (0.8 – 2.5) 8.2 (1.5 – 10) 14 (7.98 – 21) Maternal concentration of TNFi in the 2nd trimester, median±IQR (µg/ml) 22.52 (13 – 30.72) 1.4 (0.89 – 2.7) 6 (4.5 – 7.5) 6.37 (4.2 – 20) Maternal concentration of TNFi in the 3rd trimester, median±IQR (µg/ml) 20.5 (13 – 29.58) 0.2 (0.2 – 0.67) 0.85 (0.1 – 1.4) 1.4 (0.09 – 1.9) Concentration of TNFi in the cord blood if measurable, median±IQR (µg/ml) 0.25 (0.15 – 1.3) - 0.45 (0.15 – 0.65) 0.4 (0.12 – 1.15) Disclosure of Interests: Erik Kemper: None declared, Nafise Ghalandari: None declared, Hubertina Johanna Maria Josephina Crijns: None declared, Hieronymus TW Smeele: None declared, Radboud Dolhain Speakers bureau: UCB, Roche, Abbvie, Genzyme, Novartis, Consultant of: Galapagos, Grant/research support from: UCB