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Pediatric Recurrent Pericarditis: Appropriateness of the Standard of Care and Response to IL-1 Blockade - 05/05/23

Doi : 10.1016/j.jpeds.2022.11.034 
Roberta Caorsi, MD 1, , Antonella Insalaco, MD 2, , Francesca Bovis, PhD 3, Giorgia Martini, MD 4, Marco Cattalini, MD, PhD 5, Marcello Chinali, MD 6, Alessandro Rimini, MD 7, Chiara Longo, MD 8, Silvia Federici, MD, PhD 2, Camilla Celani, MD 2, Giovanni Filocamo, MD, PhD 9, Rita Consolini, MD 10, Maria Cristina Maggio, MD 11, Gloria Fadanelli, MD 12, Francesco Licciardi, MD 13, Micol Romano, MD 14, Barbara Lia Teruzzi, MD 15, Andrea Taddio, MD, PhD 16, Angela Miniaci, MD 17, Francesco La Torre, MD 18, Alessandro De Fanti, MD 19, Giulio Cavalli, MD 20, Barbara Bigucci, MD 21, Romina Gallizzi, MD 22, Matteo Chinello, MD 23, Massimo Imazio, MD 24, Antonio Brucato, MD 25, Rolando Cimaz, MD 26, Fabrizio De Benedetti, MD 2, , Marco Gattorno, MD 1,
1 Center of Autoinflammatory Diseases and Immunodeficiencies, Department of Pediatrics and Rheumatology, IRCCS Istituto G. Gaslini, Genova, Italy 
2 Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy 
3 Department of Health Sciences (DISSAL), University of Genoa, Genova, Italy 
4 Pediatric Rheumatology Unit, University of Padua, Padova, Italy 
5 Pediatrics Clinic, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy 
6 Pediatric Cardiology e Cardio-Surgery, IRRCS Ospedale Pediatrico Bambino Gesù, Roma, Italy 
7 Department of Cardiology, IRCCS Istituto G. Gaslini, Genova, Italy 
8 Department of Pediatrics, University of Genoa, Genova, Italy 
9 Division of Pediatric Immunology and Rheumatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy 
10 Department of Pediatrics, Università di Pisa, Pisa, Italy 
11 University Department PROMISE “G. D’Alessandro”, University of Palermo, Italy 
12 Division of Pediatrics, Ospedale Santa Chiara, Trento, Italy 
13 Immuno-Rheumatology Unit, Ospedale Infantile Regina Margherita, Torino, Italy 
14 ASST G. Pini-CTO, Milan, Italy 
15 Department of Pediatric Rheumatology, ASST GOM Niguarda Milano, Milan, Italy 
16 Institute for Maternal and Child Health IRCCS "Burlo Garofolo" and Univeristy of Trieste, Trieste, Italy 
17 Pediatric Unit, Program of Pediatric Rheumatology, Immunology and Pneumo-Allergology, Policlinico S. Orsola-Malpighi Bologna, Bologna, Italy 
18 Department of Pediatrics, Pediatric Rheumatology Section, "Giovanni XXIII" Pediatric Hospital, Bari, Italy 
19 Pediatric Rheumatology, Ospedale di Reggio Emilia, Reggio Emilia, Italy 
20 Clinical Immunology and Rheumatology Unit, Ospedale San Raffaele, Milano, Italy 
21 Division of Pediatrics, Ospedale di Rimini, Rimini, Italy 
22 Pediatric Unit, Department of Medical of Health Sciencies Magna Grecia, University of Catanzaro, Catanzaro, Italy 
23 Pediatric Onco-Ematology Unit, Azienda Ospedaliera Universitaria Integrata di Verona Ospedale Donna Bambino, Verona, Italy 
24 Cardiology, Cardiothoracic Department, University Hospital "Santa Maria della Misericordia", ASUFC, Udine, Italy 
25 L. Sacco Department of Clinical and Biomedical Science, Università degli studi di Milano, Milan, Italy 
26 Department of Clinical Sciences and Community Health and RECAP-RD, University of Milan, Italy 

Reprint requests: Roberta Caorsi, MD, Center of autoinflammatory diseases and immunodeficiencies, Department of Pediatrics and Rheumatology, IRCCS Istituto G. Gaslini, Via Gaslini 5, 16147 Genova, ItalyCenter of autoinflammatory diseases and immunodeficienciesDepartment of Pediatrics and RheumatologyIRCCS Istituto G. GasliniVia Gaslini 5Genova16147Italy

Abstract

Objective

To analyze, in a cohort of pediatric patients with recurrent pericarditis undergoing anti-interleukin (IL)-1 treatment: the agent and dosing used as first-line treatment, the long-term efficacy of IL-1 blockers, the percentage of patients achieving a drug-free remission, and the presence of variables associated with drug-free remission.

Study design

Data were collected from patients’ charts. The annualized relapse rate (ARR) was used for evaluation of treatment efficacy, and bivariate logistic regression analysis was used for variables associated with drug-free remission.

Results

Fifty-eight patients, treated between 2008 and 2018, were included in the study (mean follow-up. 2.6 years). Of the 56 patients treated with first-line drugs, 14 not responsive patients were underdosed. Fifty-seven patients were treated with anakinra: the ARR before and during daily treatment was 3.05 and 0.28, respectively (P < .0001); an increase to 0.83 was observed after the reduction/withdrawal of treatment (P < .0001). The switch from anakinra to canakinumab (5 patients) was associated to an increase of the ARR (0.49 vs 1.46), but without statistical significance (P = .215). At last follow-up, only 9 of the 58 patients had withdrawn all treatments. With the limits of a retrospective study and the heterogeneity between the patients enrolled in the study, a shorter duration of treatment with anakinra was the only variable associated with drug-free remission.

Conclusions

This study shows that most pediatric patients with recurrent pericarditis needing IL-1 blockade received an inadequate treatment with first-line agents. The effectiveness of anakinra is supported by this study, but few patients achieved drug-free remission. The different rate of response to anakinra and canakinumab may suggest a possible role of IL-1α in the pathogenesis of recurrent pericarditis.

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Keywords : pericarditis, therapy, anti-inflammatory agents nonsteroidal, colchicine, steroids, interleukin-1

Abbreviations : ARR, ESC, IL-1, NSAIDs


Plan


 R.C. received consultancy and speaker fee from SOBI and Novartis. A.I., M.C., A.R., and R.C. received speaker fee from SOBI. F.B. received teaching honoraria from Novartis. B received speaker fee from SOBI. G.F. received consultancy fee from SOBI. R.G. received speaker fee from Novartis. M.I. received speaker fee from Sobi and Kiniksa. F.B. received speaker fee and consultancy fee from SOBI and Novartis. M.G. received speaker fee, consultancy fee, and unrestricted grant from SOBI and Novartis. The other authors declare no conflicts of interest.


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