SUBCUTANEOUS ANAKINRA IN THE MANAGEMENT OF REFRACTORY MIS-C IN FRANCE

Perrine Dusser^1* Alexandre Belot^{2, 3} Fanny Bajolle⁴ Anne PAGNIER⁵ Ulrich Meinzer⁶ Frédéric Huet⁷ Soizic Tiriau⁸ Isabelle Kone-paut¹

• ¹CEREMAIA, Pediatric Rheumatology, Bicêtre university hospital, Assistance Publique-Hôpitaux de Paris, university of Paris Saclay, France
• ²Pediatric Nephrology, Rheumatology, Dermatology, Hôpital Femme Mère-Enfant, Hospices Civils de Lyon, Bron, France, France
• ³Reference Centre Of Inflammatory Rheumatism and Rare Autoimmune Diseases in Children (RAISE),, France
• ⁴Assistance Publique-Hôpitaux de Paris, M3C Department, Necker-Enfants Malades University Hospital, Université de Paris, Paris, France., France
• ⁵Department of General Pediatrics, Centre Hospitalier Universitaire de Grenoble, Grenoble, France, France
• ⁶Department of General Pediatrics, Pediatric Rheumatology and Infectious Diseases, RAISE, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, 75019 Paris, France, France
• ⁷Pediatric Department, University hospital of Dijon, France;, France
• ⁸Department of Pediatrics, hôpital Mère-Enfants, 44000 Nantes, France., France

Introduction: Multisystemic inflammatory syndrome in children (MIS-C) is a therapeutic emergency and can lead to myocardial dysfunction (17-75%) and heart failure (52%-53%). Immunoglobulins (IVIG) and corticosteroids (CST) have been validated for the management of this condition. Recent reports suggest that IL-1 receptor antagonist, namely anakinra, may be a valuable add-on to COVID-19 treatment for refractory patients. The purpose of this study was to describe the clinico-biological characteristics of patients treated with anakinra as well as the efficacy and safety of subcutaneous anakinra therapy in this condition.
Methods: Prospective multicentre study of children hospitalized for MIS-C between March 2020 and September 2022, from 23 international paediatric centres, followed for a mean duration of 3.072 ± 3.508 months. Patient data were extracted from the Juvenile Inflammatory Rheumatism (JIR) cohort. Clinico pathological characteristics, cardiac ultrasound data and adverse events were reported in patients receiving anakinra.
Results: Of 470 children admitted with MIS-C, 18 French patients (50% girls) with a mean age of 10.06 ± 3.9 years were treated with subcutaneous anakinra. Anakinra was used in two situations, macrophage activation syndrome (MAS) (4 patients) and heart failure (14 patients) with a median LVEF of 39.5% [30% - 45%]. The average dose of anakinra received was 2.53 ±1.3 mg/kg/day for a median duration of 3 days. Prior to introduction, 78% (n=14/18) of the patients had received CST and 56% (n=10/18) had received IVIG. Only 2 patients received IVIG alone and 6 received CST alone plus anakinra. In 10% of cases, IVIG was poorly tolerated from a cardiovascular point of view and was discontinued. Transient elevations in serum transaminases was noted in 4 patients on anakinra without the need for treatment or dose modification. In all patients, rapid (48 hours) improvement in myocardial function was observed (LVEF>55%) with a concomitant significant decrease in myocardial enzymes (p<0.05). All patients survived with complete recovery of cardiac function without sequelae.
Conclusions: Subcutaneous anakinra appears to be a safe and effective treatment for the management of heart failure or MAS in MIS-C patients. The value of IVIG in these two situations remains to be reviewed.