Pregnancy outcomes after maternal and paternal anti-IL-1 treatment exposure in cryopyrin associated periodic syndromes (CAPS)

Abstract

Objectives To determine the effect of paternal and maternal anti-IL-1 treatment exposures on pregnancies and neonatal outcomes in CAPS. Methods A single-center study consecutive adult CAPS patients and their partners was performed between January 2012 and July 2024. All were screened for pregnancies and anti-IL-1 exposure before conception and/or during pregnancy; teratogenic co-therapies resulted in exclusion. Data included patient characteristics, disease activity, anti-IL-1 treatment, pregnancy complications, neonatal outcomes and child health trajectories. Results Among 112 patients 11 pregnancies were recorded including eight maternal and three paternal anti-IL-1 exposures. All patients had moderate CAPS, 43% had hearing loss. At conception, all patients received canakinumab. Among the eight maternal exposures, six switched to anakinra, one refused the switch and continued canakinumab, and one had to be switched back to canakinumab due to significant local injection reactions. Pregnancy complications included one miscarriage and one preterm birth, both associated with disease activity. Neonatal outcomes were favorable, with a mean gestational age of 37 + 6 weeks and an average birth weight of 3028 g. No congenital malformations were observed. Neonatal complications included one presumed sepsis (culture negative) requiring IV antibiotics and one mild RSV infection. CAPS was diagnosed in five of 11 offspring, all of whom achieved effective disease control early, with no cases of hearing loss or amyloidosis. Conclusion In summary, the benefit risk ratio of maternal and paternal anti-IL-1 exposure during conception and pregnancy in our CAPS patients was favourable. CAPS disease activity may have a significant impact on development of pregnancy complications.