Long-Term Follow-Up and Optimization of Interleukin-1 Inhibitors in the Management of Monogenic Autoinflammatory Diseases: Real-Life Data from the JIR Cohort (original) (raw)
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Frontiers in Immunology, 2021
BackgroundInterleukin (IL)-1 inhibitors represent the main treatment in patients with colchicine-resistant/intolerant familial Mediterranean fever (crFMF), mevalonate kinase deficiency (MKD), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). However, the reasons for the use of IL-1 inhibitors in these diseases are still not completely clarified.ObjectiveIdentify real-life situations that led to initiating anakinra or canakinumab treatment in hereditary recurrent fevers (HRFs), combining data from an international registry and an up-to-date literature review.Patients and MethodsData were extracted from the JIRcohort, in which clinical information (demographic data, treatment, disease activity, and quality of life) on patients with FMF, MKD, and TRAPS was retrospectively collected. A literature search was conducted using Medline, EMBASE, and Cochrane databases.ResultsComplete data of 93 patients with HRF (53.8% FMF, 31.2% MKD, and 15.1% TRAPS) were analyzed. Dat...
Modern Rheumatology, 2014
Objectives. The aim of this report was to evaluate and discuss treatment of pediatric familial Mediterranean fever (FMF) patients with anti-interleukin1 (IL-1) agents. Methods. Refractory or colchicine unresponsive FMF was described as severe and frequent attacks and/or having high acute phase reactance levels despite having a maximum dose of colchicine (2 mg/day). Disease course, adverse eff ects, duration of follow-up, treatment protocols, responses to the therapies were discussed. Results. Eight patients (6 male, 2 female) having refractory FMF were identifi ed. Mediterranean fever (MEFV) gene analyses revealed homozygous M694V mutations in six patients and heterozygote M694V mutations in one patient and no mutation in one patient. They were all treated with anakinra and/or canakinumab. The use of anti-IL-1 drugs was benefi cial to all patients. None of them had any severe adverse eff ects due to the therapy. Conclusions. Anakinra and canakinumab were eff ective in patient refractory to colchicine treatment as shown both in our series and in the literature. Therefore, controlled trials are needed to evaluate the safety and long-term effi cacy of IL-1 targeting agents in colchicine resistant patients.
Turkish Archives of Pediatrics
Interleukin-1 inhibitors are effective agents used in colchicine resistance or intolerance during the treatment of familial Mediterranean fever. This study aims to review the characteristics of patients treated with interleukin-1 inhibitors and their long-term follow-up in a large pediatric cohort of familial Mediterranean fever patients. Materials and Methods: The study was conducted in a pediatric rheumatology reference center. The patients treated with interleukin-1 inhibitors for at least 6 months were included and compared to other patients with familial Mediterranean fever. Clinical and laboratory characteristics of the cohort were recorded. Results: Among 542 patients with familial Mediterranean fever, 6.1% (n = 33) were treated with interleukin-1 inhibitors. Colchicine resistance was the reason in 82.8% and renal amyloidosis in 17.2% of the patients. Patients with interleukin-1 inhibitors had earlier disease onset and higher frequencies of acute arthritis, chest pain, and erysipelas-like erythema with pathogenic exon 10 mutations of the MEFV gene (all P < .04). All patients diagnosed with renal amyloidosis also received interleukin-1 inhibitors. Six patients were switched from anakinra to canakinumab or vice versa to control ongoing disease activity. Attack frequency was reduced in all patients. Conclusion: Interleukin-1 inhibitors are used in a relatively small number of pediatric patients with familial Mediterranean fever. Patients presenting with earlier disease onset, acute arthritis, chest pain, and erysipelas-like erythema and carrying pathogenic exon 10 mutations of the MEFV gene may show a higher need for interleukin-1 inhibitors. In pediatric familial Mediterranean fever patients who are resistant to colchicine, interleukin-1 inhibitors seem to be highly effective agents.
Arthritis care & research, 2017
Around 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anit-IL1) agents. Herein we report our experience with the off-label use of anti-IL1 agents in a large group of FMF patients. In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL1 treatment for at least 6 months were reviewed. In total, 172 FMF patients (83 [48%] female, mean age 36.2 [range, 18-68] years old) were included in the analysis; their mean age at symptom onset was 12.6 (range; 1-48) years, and the mean colchicine dose was 1.7 (0.5-4.0) mg/day. Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL1 treatment was used because of colchicin...
Arthritis Care & Research, 2017
Objectives: Periodic fever syndromes (PFS) are characterised by recurrent attacks of fever and localised inflammation. This study examined the diagnostic pathway and treatments at tertiary centres for FMF, TRAPS and MKD/HIDS. Methods: PFS specialists at medical centres in the USA, European Union and Eastern Mediterranean participated in a retrospective chart review, providing de-identified data in an electronic case report form. Patients were treated between 2008-2012 with at least 1 year of follow-up, all had clinical and/or genetically proven disease, and were on/eligible for biologic treatment. Results: 134 patients were analysed in total: FMF (n=49), TRAPS (n=47), and MKD/HIDS (n=38). Fever was commonly reported as severe across all indications. Other frequent severe symptoms were serositis for FMF patients and elevated acute-phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 years and 7.1 years, respectively) with a 1.8 year delay in FMF. An equal proportion of TRAPS patients first received anti-IL-1 and anti-TNF biologics whereas IL-1 blockade was the main choice for MKD/HIDS and FMF patients. For TRAPS patients, treatment with anakinra versus anti-TNF treatments as first biologic resulted in significantly higher clinical and biochemical responses (p=0.03 and p<0.01, respectively). No significant differences in responses were observed between biological agents among other cohorts.
Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes
The New England journal of medicine, 2018
Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canaki...
Classification criteria for autoinflammatory recurrent fevers
Annals of the Rheumatic Diseases, 2019
BackgroundDifferent diagnostic and classification criteria are available for hereditary recurrent fevers (HRF)—familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD) and cryopyrin-associated periodic syndromes (CAPS)—and for the non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA). We aimed to develop and validate new evidence-based classification criteria for HRF/PFAPA.MethodsStep 1: selection of clinical, laboratory and genetic candidate variables; step 2: classification of 360 random patients from the Eurofever Registry by a panel of 25 clinicians and 8 geneticists blinded to patients’ diagnosis (consensus ≥80%); step 3: statistical analysis for the selection of the best candidate classification criteria; step 4: nominal group technique consensus conference with 33 panellists for the discussion and selection of the final classification criteria; step 5: cross-section...
The Journal of Rheumatology, 2018
Objectives: Provisional evidence-based classification criteria for inherited periodic fever (HPF) have been recently developed. However, no consensus on how to combine clinical criteria, laboratory test and results of molecular analysis has been reached. Objective of the study is to understand which variables physicians consider as important for the classification of patients with HPF. Methods: Two following Delphi surveys were sent to health professionals working in the field of autoinflammation. In the first open survey 124 researchers could list all the variables they consider as useful for the diagnosis of each monogenic periodic fever. The variables could be of any type and each researcher could complete the survey for one or more disease. In the second survey 162 researcher were asked to select, from a list of items coming from the first survey, the 10 top variables and to rank them by assigning a score from 10 to 1. Results: The overall rate of response to the Delphi surveys, was of 85% for both sessions. The variables selected for each disease (corresponding to the 3 rd quartile considering the total score obtained by the variables after the second Delphi survey) were respectively: 21 for MKD, 22 for CAPS, 18 for FMF, and 20 for TRAPS. A positive genetic test reached the top rank in all the HPF. Conclusion: Our process led to the identification of those features considered to be the most important as candidate variable to be included in a new set of evidence based classification criteria for HPF.