Outcomes of MIS-C patients treated with anakinra: a retrospective multicenter national study

Francesco Licciardi; Carlotta Covizzi; Marta Dellepiane; Nicole Olivini; Maria Vincenza Mastrolia; Andrea Lo Vecchio; Viviana Monno; Maria Tardi; Angela Mauro; Maria Alessio; Giovanni Filocamo; Marco Cattalini; Andrea Taddio; Roberta Caorsi; Gian Luigi Marseglia; Francesco La Torre; Andrea Campana; Gabriele Simonini; Angelo Ravelli; Davide Montin

doi:10.3389/fped.2023.1137051

Outcomes of MIS-C patients treated with anakinra: a retrospective multicenter national study

Front Pediatr. 2023 Aug 22:11:1137051. doi: 10.3389/fped.2023.1137051. eCollection 2023.

Authors

Francesco Licciardi¹, Carlotta Covizzi¹, Marta Dellepiane¹, Nicole Olivini², Maria Vincenza Mastrolia³, Andrea Lo Vecchio⁴, Viviana Monno⁵, Maria Tardi⁶, Angela Mauro⁷, Maria Alessio⁴, Giovanni Filocamo⁸, Marco Cattalini⁹, Andrea Taddio¹⁰, Roberta Caorsi¹¹, Gian Luigi Marseglia¹², Francesco La Torre⁵, Andrea Campana², Gabriele Simonini³, Angelo Ravelli¹¹, Davide Montin¹

Affiliations

¹ Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, "Regina Margherita" Children Hospital, University of Turin, Turin, Italy.
² Pediatrics Unit, University Department of Pediatrics (DEAPG), Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.
³ Rheumatology Unit, Department of Paediatrics, Meyer Children's Hospital, University of Florence, Florence, Italy.
⁴ Section of Paediatrics, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
⁵ Pediatric Rheumatology Section, Department of Pediatrics, Giovanni XXIII Pediatric Hospital, Bari, Italy.
⁶ Rheumatology Unit, Department of Pediatrics, Santobono Pausilipon Children Hospital, Naples, Italy.
⁷ COVID Unit, Emergency Department, Santobono-Pausilipon Children Hospital, Naples, Italy.
⁸ Pediatric Rheumatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy.
⁹ Spedali Civili, Unità di Immunologia e Reumatologia Pediatrica, Clinica Pediatrica dell'Università di Brescia, Brescia, Italy.
¹⁰ Institute for Maternal and Child Health "IRCCS Burlo Garofolo", Trieste and University of Trieste, Trieste, Italy.
¹¹ Clinica Pediatrica e Reumatologia, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
¹² Pediatric Clinic Foundation IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy.

Abstract

Background: The treatment of multisystem inflammatory syndrome in children unresponsive to first-line therapies (IVIG and/or steroids) is challenging. The effectiveness of IL-1 receptor antagonist, anakinra, is debated.

Patients and methods: We conducted an anonymous retrospective multicenter study on MIS-C patients treated with anakinra in Italy from January 2020 to February 2021. Our study outcomes included the percentage of patients who required further therapeutic step-up, the percentage of patients who experienced fever resolution within 24 h and a reduction of CRP by half within 48 h, and the percentage of patients who developed Coronary Artery Anomalies (CAA) during follow-up.

Results: 35 cases of MIS-C were treated in 10 hospitals. Of these, 13 patients started anakinra while in the ICU, and 22 patients started anakinra in other wards. 25 patients (71.4%) were treated with corticosteroids at a starting dose 2-30 mg/Kg/day plus IVIG (2 g/Kg), 10 patients (28.6%) received only corticosteroids without IVIG. Anakinra was administered intravenously to all patients in Group A (mean dose 8 mg/Kg/day), and subcutaneously in Group B (mean dose 4 mg/Kg/day). Only two patients required further treatment step-up and no patients developed CAA after receiving anakinra. The most commonly observed side effect was an increase in ALT, occurring in 17.1% of patients.

Conclusions: In this retrospective cohort of severe MIS-C patients treated with anakinra we report favorable clinical outcomes with a low incidence of side effects. The simultaneous use of steroids ± IVIG in these patients hinders definitive conclusions regarding the need of IL-1 inhibition in MIS-C treatment.

Keywords: COVID-19; MIS-C; SARS-CoV2; multisystem inflammatory syndrome; pediatrics.

Grants and funding

The authors declare that this study received funding from SOBI as economic support for the submission; the funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.