Véronique Hentgen1, Isabelle Koné-Paut2, Alexandre Belot3, Caroline Galeotti2, Gilles Grateau4, Aurelia Carbasse5, Anne Pagnier6, Pascal Pillet7, Marc Delord8, Michael Hofer9, Sophie Georgin-Lavialle4. 1. Department of Pediatrics, National Reference Center for Auto-inflammatory Diseases and Amyloidosis, CEREMAIA, Versailles Hospital, Versailles, France. 2. Department of Pediatric Rheumatology National Reference Center for Auto-Inflammatory Diseases and Amyloidosis, CEREMAIA, CHU du Kremlin Bicêtre, University of Paris Sud Saclay, UVSQ, Le Kremlin Bicêtre, France. 3. Pediatric Nephrology, Rheumatology, Dermatology, HFME, Hospices Civils de Lyon, National Referee Centre RAISE, & INSERM U1111, Université de Lyon, Lyon, France. 4. Department of Internal Medicine, National Reference Center for Auto-Inflammatory Diseases and Amyloidosis, CEREMAIA, Tenon Hospital, AP-HP, Sorbonne University, Paris, France. 5. Department of Pediatrics, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France. 6. Department of Pediatrics, CHU de Grenoble, Grenoble, France. 7. Department of Pediatrics, Hôpital des Enfants, CHRU Bordeaux, Bordeaux, France. 8. Direction de La Recherche Clinique et de L'Innovation (DRCI) Versailles Hospital, Versailles, France. 9. Unité Romande D'Immuno-Rhumatologie Pédiatrique, CHUV, University of Lausanne, Lausanne, Switzerland.
Abstract
Objectives: The major role of interleukin (IL)-1 in the pathogenesis of hereditary recurrent fever syndromes favored the employment of targeted therapies modulating IL-1 signaling. However the best use of IL1 inhibitors in terms of dosage is difficult to define at present. Methods: In order to better understand the use of IL1 inhibitors in a real-life setting, our study assessed the dosage regimens of French patients with one of the four main hereditary recurrent fever syndromes (Familial Mediterranean Fever (FMF), TNF receptor associated periodic syndrome (TRAPS), cryopyrin associated periodic fever (CAPS) and mevalonate kinase deficiency). The patients were retrieved retrospectively from the JIR cohort, an international platform gathering data of patients with pediatric inflammatory diseases. Results: Forty five patients of the JIR cohort with a hereditary recurrent fever syndrome had received at least once an IL1 inhibitor (anakinra or canakinumab). Of these, 43% received a lower dosage than the one suggested in the product recommendations, regardless of the type of the IL1 inhibitor. Especially patients with FMF and TRAPS seemed to need lower treatment regimens; in our cohort none of the FMF or TRAPS patients received an intensified dose of IL-inhibitor. On-demand treatment with a short half-life IL-1 inhibitor has also been used successfully for some patients with one of these two conditions The standard dose was given to 42% of the patients; whereas an intensified dose of IL-1 inhibitors was given to 15% of the patients (44% of CAPS patients and 17% of mevalonate kinase deficiency patients). In our cohort each individual patient's need for treatment seemed highly variable, ranging from on demand treatment regimens to intensified dosage maintenance therapies depending on the activity and the severity of the underlying disease. Conclusion: IL-1 inhibitors are a good treatment option for patients with a hereditary recurrent fever syndrome, but the individual need of the dosage of IL-1 inhibitors to control the disease effectively seems highly variable. Severity, activity but also the type of the underlying disease, belong to the parameters underpinning the treat-to-target strategy implemented in an everyday life practice.
Objectives: The major role of interleukin (IL)-1 in the pathogenesis of hereditary recurrent fever syndromes favored the employment of targeted therapies modulating IL-1 signaling. However the best use of IL1 inhibitors in terms of dosage is difficult to define at present. Methods: In order to better understand the use of IL1 inhibitors in a real-life setting, our study assessed the dosage regimens of French patients with one of the four main hereditary recurrent fever syndromes (Familial Mediterranean Fever (FMF), TNF receptor associated periodic syndrome (TRAPS), cryopyrin associated periodic fever (CAPS) and mevalonate kinasedeficiency). The patients were retrieved retrospectively from the JIR cohort, an international platform gathering data of patients with pediatric inflammatory diseases. Results: Forty five patients of the JIR cohort with a hereditary recurrent fever syndrome had received at least once an IL1 inhibitor (anakinra or canakinumab). Of these, 43% received a lower dosage than the one suggested in the product recommendations, regardless of the type of the IL1 inhibitor. Especially patients with FMF and TRAPS seemed to need lower treatment regimens; in our cohort none of the FMF or TRAPS patients received an intensified dose of IL-inhibitor. On-demand treatment with a short half-life IL-1 inhibitor has also been used successfully for some patients with one of these two conditions The standard dose was given to 42% of the patients; whereas an intensified dose of IL-1 inhibitors was given to 15% of the patients (44% of CAPS patients and 17% of mevalonate kinasedeficiencypatients). In our cohort each individual patient's need for treatment seemed highly variable, ranging from on demand treatment regimens to intensified dosage maintenance therapies depending on the activity and the severity of the underlying disease. Conclusion: IL-1 inhibitors are a good treatment option for patients with a hereditary recurrent fever syndrome, but the individual need of the dosage of IL-1 inhibitors to control the disease effectively seems highly variable. Severity, activity but also the type of the underlying disease, belong to the parameters underpinning the treat-to-target strategy implemented in an everyday life practice.
Authors: Jurgen Sota; Antonio Vitale; Antonella Insalaco; Paolo Sfriso; Giuseppe Lopalco; Giacomo Emmi; Marco Cattalini; Raffaele Manna; Rolando Cimaz; Roberta Priori; Rosaria Talarico; Ginevra de Marchi; Micol Frassi; Romina Gallizzi; Alessandra Soriano; Maria Alessio; Daniele Cammelli; Maria Cristina Maggio; Stefano Gentileschi; Renzo Marcolongo; Francesco La Torre; Claudia Fabiani; Serena Colafrancesco; Francesca Ricci; Paola Galozzi; Ombretta Viapiana; Elena Verrecchia; Manuela Pardeo; Lucia Cerrito; Elena Cavallaro; Alma Nunzia Olivieri; Giuseppe Paolazzi; Gianfranco Vitiello; Armin Maier; Elena Silvestri; Chiara Stagnaro; Guido Valesini; Marta Mosca; Salvatore de Vita; Angela Tincani; Giovanni Lapadula; Bruno Frediani; Fabrizio De Benedetti; Florenzo Iannone; Leonardo Punzi; Carlo Salvarani; Mauro Galeazzi; Rossella Angotti; Mario Messina; Gian Marco Tosi; Donato Rigante; Luca Cantarini Journal: Clin Rheumatol Date: 2018-05-17 Impact factor: 2.980
Authors: Samuel Deshayes; Sophie Georgin-Lavialle; Arnaud Hot; Cécile-Audrey Durel; Eric Hachulla; Nicolas Rouanes; Sylvain Audia; Thomas Le Gallou; Pierre Quartier; Geoffrey Urbanski; Laurent Messer; Stéphane Klein; Hubert de Boysson; Boris Bienvenu; Gilles Grateau; Achille Aouba Journal: J Rheumatol Date: 2018-01-15 Impact factor: 4.666