Exposure during pregnancy to Il-1 targeted therapies and pregnancy, foetal and neonatal outcomes: a study from the French Teratology Information Service.

Abstract

To describe the outcomes of pregnancies exposed to IL-1 targeted therapies (anti-IL-1): anakinra and/or canakinumab. We performed a descriptive observational study based on data from CRAT, the French Teratology Information Service. We included prospective and retrospective pregnancies exposed to anakinra and/or canakinumab with known outcomes. Pregnancy, foetal and neonatal outcomes were analysed. Between 2007 and 2023, 57 pregnant women exposed to anti-IL-1 were referred, including 27 (47.3%) treated for Still's disease. Among prospective cases, 52 foetuses (one twin pregnancy) were exposed to anakinra (n = 43), canakinumab (n = 5) or both medications (n = 4). For anakinra: (i) 40/47 cases (85.1%) were exposed during the first trimester (T1), and 21/47 (44.7%) during all pregnancy, (ii) 40/47 (85.1%) resulted in livebirths, 5/47 (10.6%) early miscarriages, one medical abortion (mother-transmitted syndrome) and one elective abortion, (iii) one isolated hypospadias was reported (anakinra between 0 and 4 weeks of gestation), for a prevalence of major congenital malformation of 3.03% IC 95% [0.1-15.1] among T1-exposed pregnancies. For canakinumab, all cases (9/9) were exposed during T1 and 2/9 during all pregnancy: all resulted in livebirths with no malformation. Concerning retrospective pregnancies (anakinra = 6/6), all resulted in live births. Cardiopathy with hypospadias was identified in a child with a rare genetic anomaly. No significant effects were reported while breastfeeding (n = 9). In this study, the largest series to date, our results do not suggest occurrence of specific negative outcomes in pregnancies exposed to anti-IL-1. The imputability of anakinra in the malformations observed is unlikely. If needed, their use during pregnancy should be considered.