Colchicine-resistant Familial Mediterranean Fever: triggering factors are highly prevalent and reduced under IL-1 inhibition

Article title: Do we consider enough the presence of triggering factors in the evaluation of patients with FMF? Triggering factors are highly prevalent in colchicine-resistant FMF patients.

First author: Bayram Farisogullari

Journal: Internal and Emergency Medicine

Link to the article: https://pubmed.ncbi.nlm.nih.gov/38103114/

Introduction

The objective of this study was to investigate the frequency of triggering factors in patients with Familial Mediterranean Fever (FMF) who are resistant to colchicine and in those who are responsive to colchicine, and to assess the impact of interleukin-1 (IL-1) antagonist therapy on triggering factors in colchicine-resistant patients.

Patients and Methods

Colchicine-resistant FMF patients treated with IL-1 antagonists and colchicine-responsive patients treated with colchicine and experiencing ≤ 3 attacks in the previous year were questioned about the presence of 12 different triggering factors: cold exposure, emotional stress, fatigue, intense physical activity, menstruation (for women), sleep deprivation, prolonged standing, long-distance travel, high-fat diet, prolonged fasting, infections, and trauma.

Colchicine-resistant patients were questioned for two periods: before and after initiation of IL-1 antagonist therapy.

Results

A total of 63 patients were included, comprising 28 colchicine-resistant patients (19 treated with anakinra and 9 with canakinumab) and 35 colchicine-responsive patients. Only half carried two pathogenic mutations in exon 10 of the MEFV gene (Table 1). Overall, 77.8% of patients reported at least one triggering factor, with a mean number of 2.6 per patient.

The most common triggering factors, in decreasing order of frequency, were emotional stress, menstruation, cold exposure, prolonged standing, and long-distance travel. Triggering factors accounted for approximately one-third of attacks, and 57.1% of patients reported using avoidance strategies. The frequency of triggering factors was higher in colchicine-resistant patients than in colchicine-responsive patients (89.3% vs 68.6%; p = 0.04).

Among colchicine-resistant patients, the frequency of triggering factors decreased from 89.3% to 32.1% under IL-1 antagonist therapy, and the proportion of attacks initiated by a triggering factor decreased from 27.8% to 14.4% (p < 0.001) (Table 2).

Discussion

Triggering factors were more frequent in colchicine-resistant patients than in colchicine-responsive patients. Treatment with IL-1 antagonists appeared to reduce both the number of triggering factors and the proportion of attacks induced by these factors.

Conclusion

Triggering factors are common in FMF and should be systematically assessed, particularly when colchicine resistance develops. IL-1 antagonists reduce their impact and may be useful as long-term therapy or as preventive treatment during predictable exposures.

Characteristics of familial Mediterranean fever after 65 years of age

First author: François Rodrigues et al.

Link to article: https://doi.org/10.1016/j.ejim.2024.10.010

              Familial Mediterranean Fever (FMF) is an autosomal recessive disease caused by mutations in MEFV, characterized by recurrent febrile attacks. The natural history of the disease, which began in children and had a high mortality rate in the last century, is unknown in people over 65.

        This retrospective study included the records of 59 patients with FMF followed at Hôpital Tenon (Paris, France), representing 9% of the total number of patients followed for FMF. The median age was 73 years. Although all patients were treated with colchicine, the study population, born in the 1940s-1950s, had a late diagnosis (median age 28 years) and a delayed initiation of colchicine (35 years, median year of introduction 1980). 73% of patients had an elevated intercritical CRP on colchicine, and 37% had to receive an inteleukin-1 inhibitor, with good tolerability. The prevalence of AA amyloidosis was 10%. The most frequent comorbidities were cardiovascular (59% of patients) and, unexpectedly, hepatic (37%), with a high frequency of non-alcoholic, non-viral cirrhosis (27%) and no associated diabetes, suggesting a link with FMF. Nine patients (15%) had died at the time of collection, two from complications of FMF, two from hepatic cirrhosis, and five from infections.

             In conclusion, the study indicates that FMF can remain active after the age of 65, motivating specialized lifelong follow-up with CRP monitoring between attacks, as well as the prescription of biotherapy in the event of unsatisfactory disease control.

Caractéristiques de la fièvre méditerranéenne familiale après 65 ans.pdf

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Canakinumab treatment real world evidence in 3 monogenic periodic fever syndromes in 2009-2022: an interim analysis using the French JIR cohort database

First author: Isabelle Koné-Paut et al.

Link to article: DOI: 10.1186/s13075-024-03316-7

Abstract

Background: Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in 3 monogenic periodic fever syndrome: Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS).

Methods: This study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study.

Results: 31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab.

Conclusion: This interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.

Canakinumab treatment real world evidence.pdf

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