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.

Familial Mediterranean Fever: a single dose of anakinra to stop an acute attack

Article title: A single dose of anakinra for arresting Familial Mediterranean Fever attacks: a proof-of-concept study

First author: E. Giat

Journal: Clinical and Experimental Rheumatology

Link to the article: https://pubmed.ncbi.nlm.nih.gov/41133353/

Author of the abstract: Dr Catherine Grandpeix-Guyodo

Introduction

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is characterized by recurrent febrile attacks of serositis (peritonitis, pleuritis, arthritis) and may, in the long term, be complicated by AA amyloidosis in cases of uncontrolled chronic inflammation. Colchicine is the standard long-term treatment; however, some patients experience incomplete response or intolerance, leading to the continuous use of IL-1 inhibitors (anakinra or canakinumab). Nevertheless, acute attacks may still occur despite treatment, and their management remains largely symptomatic, with limited efficacy of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs).

Patients and Methods

The objective of this prospective study was to evaluate the efficacy of a single dose of anakinra (100 mg subcutaneously) administered at the onset of an attack to interrupt its progression. The study included patients with typical FMF according to Tel Hashomer criteria, carrying one or two pathogenic MEFV mutations, treated with colchicine, and having experienced at least two serositis attacks in the previous year. Patients receiving continuous anti–IL-1 therapy were excluded, as were those with atypical attacks or chronic inflammatory states.

Patients were provided with a prefilled syringe of anakinra and received training in self-injection and early recognition of attack symptoms. The duration of treated attacks was compared with each patient’s usual attack duration.

Results

Thirty-five patients agreed to participate: five were excluded due to persistent inflammation; four experienced no attacks during the study period; two did not ultimately use anakinra during an attack; and one discontinued due to an adverse event. A total of 23 patients were analyzed, including 13 with two pathogenic MEFV mutations (considered to have “classical” FMF) and 10 with a single pathogenic MEFV mutation (considered “heterozygous” FMF).

The mean duration of treated attacks was 8.3 ± 6.8 hours, compared with 56.3 ± 16.8 hours under usual conditions. When anakinra was injected within the first 4 hours of attack onset, 85% of attacks were interrupted within 4 hours after injection. Later injections resulted in a less pronounced but still significant reduction compared with usual attack duration. Overall, 91% of treated attacks lasted less than 24 hours. Only one adverse event was reported (local injection-site reaction), highlighting the good tolerability of this strategy.

Six patients continued to use self-purchased anakinra to treat 43 additional attacks, with similar results, confirming the reproducibility and feasibility of this approach in real-life conditions.

Discussion

The authors emphasize that this strategy is not an alternative to continuous treatment in colchicine-resistant or -intolerant patients. Rather, it should be considered a “rescue” therapy, allowing rapid interruption of occasional acute attacks, reduction of pain, avoidance of emergency department visits, decreased absenteeism, and improved quality of life.

Conclusion

This prospective study demonstrates the efficacy and safety of a single, early injection of anakinra to significantly shorten FMF attacks (both classical and heterozygous forms) in adults. A randomized controlled trial is currently underway to confirm these findings and to better define the optimal role of this strategy within the therapeutic armamentarium.

Living with Familial Mediterranean Fever (FMF): what helps you cope better?

Article title: The effects of self-efficacy in managing the disease and disease adaptation levels of Familial Mediterranean

Fever (fmf) patients on satisfaction with life: a web-based cross-sectional study

First author: Demir RN

Journal: Orphanet Journal of Rare Diseases

Link to the article: https://ojrd.biomedcentral.com/articles/10.1186/s13023-025-03931-w

Author of the abstract: Rim BOURGUIBA

Abstract

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease in the world. It is characterized by recurrent inflammatory episodes of fever, abdominal pain, chest pain, and joint pain. Treatment is based on colchicine as first-line therapy, with biotherapy sometimes necessary. In addition to medical management, patients' ability to adapt to chronic disease and their sense of self-efficacy, defined as their feeling of personal effectiveness in managing the disease, can influence their quality of life. The objective of this study was to evaluate the impact of self-efficacy in FMF management and levels of adaptation to the disease on the satisfaction/quality of life of patients with FMF.

Methods:

A cross-sectional observational study was conducted using an online questionnaire distributed on Facebook and Instagram (FMF patient groups) between February and April 2024. The authors included adult Turkish patients (≥18 years old) who had been diagnosed at least one year prior.

The assessment tools used were:

- Self-Efficacy Scale for Chronic Disease (6 items).

- Adaptation to Chronic Illness Scale (25 items: physical, psychological, and social adaptation).

- Satisfaction With Life Scale.

Results

In this study of 423 adult Turkish patients with FMF, there was a predominance of females (73.8%), with ages ranging from 32 to 45 years. A disease duration of 21 years or more was reported in 38.3% of patients. The average self-efficacy score in disease management was relatively high (4.67/10). Adaptation to the disease was moderate overall (3.10/5), with better physical adaptation (3.36), followed by psychological adaptation (2.92) and social adaptation (2.87). Life satisfaction was below average (2.68/5). The correlation study revealed positive and significant associations between self-efficacy and adaptation (r = 0.532), between self-efficacy and life satisfaction (r = 0.417), and between adaptation and life satisfaction (r = 0.564) (Table 1). Regression analysis showed that self-efficacy explained 17.4% of the variance in life satisfaction, while adaptation to the disease explained 31.8%, confirming their decisive role in the self-management of FMF on quality of life (Table 2).

Conclusion

This study shows that in patients with FMF, self-efficacy and adaptation to the disease directly influence the overall low quality of life in this population. Strengthening therapeutic education and psychosocial support appears essential to improving the quality of life of adult patients with FMF.

Table 1: Correlation study between self-efficacy and quality of life in FMF patients

Table 2: Regression analysis of self-efficacy on quality of life and disease management

Vivre avec la fièvre méditerranéenne familiale : qu’est-ce qui aide à mieux s’en sortir.pd

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