Background: Interleukin-1 (IL-1) inhibitors, including anakinra and canakinumab, are effective treatments for autoinflammatory diseases such as adult-onset Still’s disease (AOSD) and familial Mediterranean fever (FMF). These diseases often affect women of reproductive age, raising concerns about the safety of anti-IL1 therapies during pregnancy. Although data suggest no significant malformation or neonatal risks, prospective evidence remains limited [1].

Objectives: To prospectively evaluate maternal and neonatal outcomes in pregnancies exposed to anti-IL-1 inhibitors, focusing on complications, preterm birth and long-term infant health.

Methods: This study analysed women from the GR2 cohort, a French multicentre prospective registry of women with rare and/or rheumatological diseases. Pregnancies with periconceptional (canakinumab in the two months before conception and anakinra at the theoretical date of conception) or gestational exposure to anakinra or canakinumab were included. The prospective registry began in 2014 and we froze inclusions in February 2024 for this work. Data included disease activity, treatment, pregnancy outcomes and neonatal health, with follow-up data on child development.

Results: We included 37 pregnancies (including 3 twin pregnancies) in 31 patients exposed to anti-IL-1 (anakinra in 33 and canakinumab in 4). The underlying maternal autoinflammatory diseases were AOSD (n=17), FMF (n=16), unspecified systemic autoinflammatory disease (n=2), cryopyrin-associated autoinflammatory syndrome (n=1), TNF receptor associated periodic syndrome (n=1), recurrent pericarditis (n=1), respectively. One patient had both FMF and AOSD. Pregnant women were exposed to anti-IL-1 for a median duration of 26 weeks [6; 37.4], with the majority of patients treated in the periconceptional period and continuing into the third trimester for anakinra. Fifteen patients (41%) had at least one pregnancy-related complication. Eight women had infections (appendicitis, COVID infection, bronchitis, otitis externa, sialadenitis and pyelonephritis) with no required intensive care treatment reported (22%), 5 gestational diabetes (14%), 5 intrahepatic cholestasis (14%), 3 threatened preterm delivery (8%) but pregnancy finally carried to term, 2 intrauterine growth retardation (5%) and one woman presented pre-eclampsia (3%). One patient with uncontrolled FMF had two early spontaneous miscarriages (5%), both at the time of the crisis. Preterm delivery occurred in 14% of cases, all between 32 and 37 weeks of amenorrhea, with no extreme prematurity. Despite treatment, disease flares occurred in 72% of the pregnancies. Neonates had weighted 3 220 grams [2873; 3398], with only one singleton classified as small for gestational age. No malformations were observed. During the first days of life, one infant had an infection associated with stained amniotic fluid, one had neonatal still’s disease, and one had neonatal jaundice. All the 32 neonates followed until the 6-month follow up, were healthy, three were reported to have infections, one had laryngomalacia and one required surgery for an inguinal hernia. Twenty-two patients were followed more than six months with a median of 15 months after birth [12; 27]: all children were reported to be in good health with normal psychomotor development. Twenty mothers (53%) breastfed (mixed and exclusive).

Conclusion: Anti-IL-1 therapy during pregnancy in women with systemic autoinflammatory diseases appears to be safe, particularly for anakinra for which we have had the vast majority of pregnancies exposed to anti IL1 with low maternal and neonatal risks. Control of the underlying disease is a key factor in preventing complications. These findings provide reassuring evidence for the use of anakinra and canakinumab in pregnancy.

REFERENCES: [1] Faure-Bardon V, Beghin D, Latour M, Coulm B, Vauzelle C, Elefant E, et al. [Use of anti-IL-1 drugs during pregnancy]. Gynecol Obstet Fertil Senol. 16 avr 2024;S2468-7189(24)00194-6.

Acknowledgements: NIL.

Disclosure of Interests: Marion Delplanque: None declared , Léa Savey: None declared , Vincent Sobanski: None declared , Estibaliz Lazaro: None declared , Anne Murarasu grants from GSK et Chugai for attending meeting, René-Marc Flipo: None declared , Olivier Fain: None declared , Eric Hachulla: None declared , Véronique Le Guern: None declared , Benoit Marin: None declared , Delphine Beghin: None declared , Gaelle Guettrot Imbert: None declared , Anna Moltó: None declared , Nathalie Costedoat-Chalumeau BMS for a board, Roche et UCB for the institution, Sophie Georgin-Lavialle novartis and sobi.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.