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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


La Fièvre Méditerranéenne Familiale (FMF)






















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.


Figure 01
Figure 02

 
 
 

First author : Ozen S

Review: Annals of the Rheumatic Diseases

Reference: Ann Rheum Dis. 2025 Apr 9:S0003-4967(25)00084-6

Link to pubmed: EULAR/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update - PubMed

Recommandations approuvées par l’EULAR et la PReS pour la FMF

2024 European Recommendations on Familial Mediterranean Fever (FMF) – Summary:


Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. Due to its clinical and genetic variability, specialized management is essential. In 2024, the EULAR and PReS societies updated their guidelines.


General Principles:

  • FMF requires specialist expertise for both diagnosis and management.

  • The primary goal is complete control of inflammation, including subclinical inflammation, to prevent complications such as AA amyloidosis.

  • Lifelong treatment is necessary, with strict adherence, primarily based on daily colchicine therapy.

  • Care should be patient-centered, aiming to preserve quality of life.


Key Recommendations:

  • Colchicine should be initiated as soon as a clinical diagnosis is made.

  • The dosage must be tailored to tolerance and adherence (single or divided daily doses).

  • If symptoms persist or subclinical inflammation remains, the dose should be increased within recommended limits (maximum 2 mg/day in children, 3 mg/day in adults).

  • If colchicine fails despite good adherence, interleukin-1 blockers (anakinra, canakinumab) are recommended.

  • Chronic musculoskeletal manifestations may require additional treatments (DMARDs, biologics).

  • Regular monitoring (clinical, biological, toxicity, adherence) is essential.

  • Colchicine should be continued during pregnancy and breastfeeding.

  • During acute attacks, colchicine should be maintained at the same dose, with symptomatic treatment added (e.g., NSAIDs).

  • A minimum core set of assessment criteria is proposed: attack frequency, quality of life, biological markers (CRP, SAA).


Quality indicators, clinical priorities (especially adherence), and implementation strategies are provided to harmonize care across centers.



 
 
 

Author: Di Cola et al.

Ref : Di Cola et al, Arthritis Res Ther. 2025 Mar 19;27(1):59.


La dose quotidienne nécessaire de colchicine chez les patients atteints de Fièvre Méditerranéenne Familiale pourrait être plus élevée chez les femmes

Summary


To date, no data exist on the relationship between daily colchicine dosage and body weight in patients with Familial Mediterranean Fever (FMF). This question is frequently raised by patients or their parents during consultations. The objective of our study was to describe the daily colchicine dosage in a cohort of patients with FMF.


We conducted a retrospective analysis from 2016 to 2023 on adult FMF patients who were prospectively followed at the French National Reference Center for Auto-inflammatory Diseases at Tenon Hospital.


Among the 272 patients studied, 149 were women (57.8%), with a mean age of 43 years. The average weight was 67.8 kg, and the mean BMI was 24.2 kg/m². Colchicine was taken by 96% of the patients. A subgroup of 30 patients was receiving 2.5 mg/day of colchicine: the majority were women (n=23; 76.7%; p=0.018), with a significantly lower average weight (p=0.019); in fact, 26 out of 30 (87%) weighed less than 50 kg. Female sex was associated with a higher daily dose of colchicine (p=0.0208), whereas no significant correlation was found with weight (p=0.4073).


No signs of toxicity were observed in patients receiving 2.5 mg/day of colchicine, including those weighing under 50 kg, the majority of whom were women.


One hypothesis is that this increased need for colchicine in some women may be related to hormonal factors, with a possible hyperactivation of pyrin.


This is the first study to examine the relationship between weight and colchicine dosage in adults with FMF, highlighting a potential link with female sex.


This work provides reassurance to patients receiving 2.5 mg/day of colchicine: there is no toxicity at this dose in the absence of renal impairment.




 
 
 
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