Defining colchicine resistance/intolerance in patients with familial Mediterranean fever: a modified-Delphi consensus approach

Özen, Seza; Sağ, Erdal; Ben-Chétrit, Eldad; Gattorno, Marco; Gül, Ahmet; Hashkes, Philip J.; Koné‐Paut, Isabelle; Lachmann, Helen; Tsitsami, Elena; Twilt, Marinka; Benedetti, Fabrizio; Kuemmerle‐Deschner, Jasmin

doi:10.1093/rheumatology/keaa863

Cited by 44 publications

(30 citation statements)

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“…Alternative treatment options were also identified for resistant cases. Resistance to colchicine therapy was defined as ≥1 attack per month despite receiving the maximum tolerated dose for ≥6 months ( 13 , 15 ). According to the recommendations ( 13 ), the colchicine dose was calculated from 1.2 mg/m 2 /day.…”

Section: Methodsmentioning

confidence: 99%

Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort

et al. 2022

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Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting phenotypic heterogeneity. It is a clinically diagnosed disease supported by MEditerranean FeVer (MEFV) gene mutation analysis. However, the phenotype-genotype correlation is not yet established clearly. We aimed to determine the clinical findings, phenotype-genotype correlation, and treatment outcomes within a large pediatric FMF cohort. The medical charts of children with FMF who were diagnosed and followed up at the eight pediatric rheumatology units were reviewed retrospectively. All patients in the cohort were analyzed for sequence variants in exon 2,3,5 and 10 of the MEFV gene. Patients without any mutations or with polymorphisms including R202Q were excluded. A total of 3,454 children were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 12.1 ± 5.2, 5.1 ± 3.8, and 7.3 ± 4.0 years, respectively. Of 3,454 patients, 88.2% had abdominal pain, 86.7% had fever, 27.7% had arthritis, 20.2% had chest pain, 23% had myalgia, and 13.1% had erysipelas-like erythema. The most common MEFV mutation patterns were homozygous (32.5%) and heterozygous (29.9%) mutations of exon 10. Homozygous M694V was present in 969 patients (28.1%). Allele frequencies of common mutations were M694V (55.3%), M680I (11.3%), V726A (7.6%), and E148Q (7.2%). Children carrying homozygous or compound heterozygous exon 10 mutations had an earlier age of disease onset (4.6 vs. 5.6 years, p = 0.000) and a higher number of attacks per year (11.1 vs. 9.6, p = 0.001). Although 8% of the patients had a family history of amyloidosis, 0.3% (n = 11) had the presence of amyloidosis. M694V homozygosity was detected in nine patients who developed amyloidosis. Colchicine resistance was present in 4.2% of our patients. In this largest pediatric cohort reviewed and presented to date, patients with exon 10 mutations, particularly the M694V homozygous mutation, have been demonstrated earlier disease onset, annual attack count, and more frequent colchicine-resistant cases. Although E148Q is considered as a polymorphism in some populations, it was identified as a disease-causing mutation in our cohort. Secondary amyloidosis is still happening in adults however, it is extremely rare among children, presumably due to increased awareness, tight control, and the availability of anti-IL1 agents in colchicine-resistant cases.

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Section: Methodsmentioning

confidence: 99%

Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort

et al. 2022

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“…Hair colchicine testing was recently proposed ( 136 ) to assess objectively and non-invasively adherence from 2 to 6 months before the sampling. Toxicity of colchicine is rare in our study, as approved by experts in the literature ( 129 ).…”

Section: Discussionmentioning

confidence: 69%

“…According to the Franco-Israeli consortium, crFMF is defined as the occurrence of six or more typical attacks in 1 year or three in 4-6 months associated with an increase in inflammatory markers between attacks (126); according to European Alliance of Associations for Rheumatology (EULAR) definition, as at least one flare per month in the last 6 months with full compliance to treatment (127) and as more than six attacks per year or more than four attacks in the last 6 months with persistent biological inflammation (128). Recently, Ozen et al (129) agreed that crFMF included recurrent attacks (one or more attacks per month over 3 months) or persistent laboratory inflammation in-between attacks. Eighty-two percent of patients receiving IL1 inhibitors were considered crFMF in our study, similar to results (89%) of Kacar et al (130).…”

Section: Discussionmentioning

confidence: 99%

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Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review

et al. 2021

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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. Data from both the registry and the literature review confirmed that the main reasons for use of IL-1 blockers were the following: failure of previous treatment (n = 57, 61.3% and n = 964, 75.3%, respectively), persistence of disease activity with frequent attacks (n = 44, 47.3% and n = 1,023, 79.9%) and/or uncontrolled inflammatory syndrome (n = 46, 49.5% and n = 398, 31.1%), severe disease complication or associated comorbidities (n = 38, 40.9% and n = 390, 30.4%), and worsening of patients’ quality of life (n = 36, 38.7% and n = 100, 7,8%). No reasons were specified for 12 (16.4%) JIRcohort patients and 154 (12%) patients in the literature.ConclusionIn the absence of standardized indications for IL-1 inhibitors in crFMF, MKD, and TRAPS, these results could serve as a basis for developing a treat-to-target strategy that would help clinicians codify the therapeutic escalation with IL-1 inhibitors.

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“…Colchicine is the frontline therapy to suppress inflammation and prevent attacks and complications in FMF [11]. Colchicine resistance, defined as one or more attacks per month during three months or persistent systemic inflammation between attacks, is detected in about 5% of patients [12][13][14]. Biological drugs, especially anti-IL-1 agents, are used to treat colchicine resistant/intolerant patients [15].…”

Section: Fmf Diagnosis Is Mainly Based On Clinical Presentations Mefv Gene Analysis Could Support the Clinical Diagnosismentioning

confidence: 99%

Similarities and Differences Between Familial Mediterranean Fever and Behçet’s Disease

Akça

Batu

2021

CAJMHE

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Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease, mainly affecting populations originating from the Eastern Mediterranean region. Behçet’s Disease (BD) is grouped in polygenic autoinflammatory diseases. It is a systemic vasculitis that affects all types and sizes of blood vessels. The aim of this article is to shed light on similarities and differences between FMF and BD. BD is frequently reported along the ancient Silk Road, extending from the Far East to the Mediterranean basin. Several studies have searched for the association between FMF and BD. FMF is caused by mutations of the MEditerranean FeVer (MEFV) gene while an increased frequency of MEFV mutations is reported in BD patients. Although BD and FMF share some epidemiological and pathophysiological features, there are distinct clinical characteristics of these nosological entities. Mucocutaneous manifestations, especially recurrent oral ulcers, are the most common symptom in BD patients whereas fever accompanied by serosal inflammation is the main clinical presentation in FMF patients.

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Defining colchicine resistance/intolerance in patients with familial Mediterranean fever: a modified-Delphi consensus approach

Cited by 44 publications

References 29 publications

Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort

Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort

Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review

Similarities and Differences Between Familial Mediterranean Fever and Behçet’s Disease

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