Long-Term Follow-Up and Optimization of Interleukin-1 Inhibitors in the Management of Monogenic Autoinflammatory Diseases: Real-Life Data from the JIR Cohort

Frontiers in Pharmacology

Caroline Galeotti¹  Aurelia Carbasse²  Gilles Grateau³  Isabelle Koné-Paut³  Pascal Pillet⁴  Anne Pagnier⁵  Marc Delord⁶  Véronique Hentgen⁷  Michael Hofer⁸  Alexandre Belot⁹  Sophie Georgin-Lavialle^1,10 

[1] INSERM U1111, Université de Lyon, Lyon, France;Department of Internal Medicine, National Reference Center for Auto-Inflammatory Diseases and Amyloidosis, CEREMAIA, Tenon Hospital, AP-HP, Sorbonne University, Paris, France;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;Department of Pediatrics, CHU de Grenoble, Grenoble, France;Department of Pediatrics, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France;Department of Pediatrics, Hôpital des Enfants, CHRU Bordeaux, Bordeaux, France;Department of Pediatrics, National Reference Center for Auto-inflammatory Diseases and Amyloidosis, CEREMAIA, Versailles Hospital, Versailles, France;Direction de La Recherche Clinique et de L’Innovation (DRCI) Versailles Hospital, Versailles, France;;Pediatric Nephrology, Rheumatology, Dermatology, HFME, Hospices Civils de Lyon, National Referee Centre RAISE, &Unité Romande D’Immuno-Rhumatologie Pédiatrique, CHUV, University of Lausanne, Lausanne, Switzerland;

关键词: anakinra;    canakinumab;    cryopyrin-associated periodic syndrome;    Tumor Necrosis factor (TNF)-receptor-associated periodic syndrome;    mevalonate kinase deficiency;    posology;   

DOI  :  10.3389/fphar.2020.568865

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown