Pos1183 Pregnancy Outcomes in Caps Patients on Il-1 Inhibition

Background: In Cryopyrin-Associated Periodic Syndromes (CAPS), IL-1 inhibition has been proven to control disease activity and improve quality of life. With good disease management on IL-1 inhibition during reproductive age, effects on fertility and potential risks during pregnancy become crucial. Limited safety data is available about effects of IL-1 inhibition on conception, pregnancy, or breastfeeding. Objectives: To evaluate pregnancy outcomes in CAPS patients exposed to IL-1 inhibitors before and during pregnancy. Methods: In this single-center retrospective study, seven pregnancies from four CAPS patients are described. Patient characteristics include age at initial diagnosis, pre-pregnancy disease status, medications, organ involvement, and genetic mutations. Detailed analyses encompass aspects of the pregnancy processes, complications, IL-1 inhibitor type and dosage, therapy adjustments, primary disease status during pregnancy, and fetal outcomes including gestational age at delivery, birth weight, APGAR score, anomalies, and neonatal events. Results: Patient profiles and disease activity: Four female CAPS-patients (two patients with a likely pathogenic E311K mutation, one with a pathogenic R260W mutation and one with a pathogenic T348M mutation) participated in the study, which included a total of seven pregnancies. Hearing loss was present at diagnosis in two patients with the likely pathogenic E311 mutation. The median age at diagnosis was 22.2 years (IQR: 18-27.2), and the median age at pregnancy was 29 years (IQR: 27-30). All patients received Anakinra for a median of one year before switching to canakinumab prior to pregnancy. The median duration of canakinumab treatment before pregnancy was 5 years (IQR: 2.5-11.25) with stable disease remission in all patients. Pregnancy progression and maternal outcomes: Anakinra was given during four pregnancies and Canakinumab during two. In one case, Anakinra was administered until the 18th week of gestation, after which it was switched to Canakinumab due to injection site reactions and leg edema. Anakinra was initially given at the standard daily subcutaneous dose of 100 mg. However, the dosage was doubled in two pregnancies due to disease activation – one patient exhibited rash, fatigue, and joint pain, while the other showed progression of hearing loss. Treatment with Canakinumab at 300 mg every 8 weeks did not result in disease activation during pregnancy, and no dose adjustment was required. In one pregnancy under Anakinra, maternal bleeding and miscarriage occurred at week 10. No other complications were reported. Fetal Outcomes: Seven live births (four girls and three boys) resulted from seven pregnancies, including one twin pregnancy. Four births were spontaneous, and three were delivered by caesarean section. The median gestational age at delivery was 37 weeks (IQR: 37-39), with a median birth weight of 2740 grams (IQR: 2060-3570) and median APGAR score of 9/9/10. No fetal anomalies were observed. One premature infant born at 28 weeks with a birth weight of 1800 grams, while the mother was on Anakinra during pregnancy, required hospitalization due to RSV bronchitis. Another child of the same mother, also on Anakinra during pregnancy, was born vaginally at 37 weeks with a birth weight of 2060 grams and classified as Small for Gestational Age (SGA), received inpatient antibiotic treatment for neonatal infection. Conclusion: This study provides valuable data to supplement the limited knowledge regarding the safety of IL-1 antagonists during pregnancy in CAPS patients. The favorable outcomes observed in the majority of pregnancies indicate that IL-1 inhibition may be continued safely in CAPS patients during their reproductive journey. REFERENCES: [1] Brien ME et al. J Clin Med. 2021;11(1):225. doi:10.3390/jcm11010225. [2] Youngstein T et al. Rheumatology (Oxford, England), 56(12), 2102–2108. doi:10.1093/rheumatology/kex305. Acknowledgements: NIL. Disclosure of Interests: Özlem Satirer: None declared, Susa Benseler: None declared, Jasmin B. Kuemmerle-Deschner SOBI/Novartis, SOBI/Novartis, SOBI/Novartis.