Efficacy and safety of anti-interleukin-1 treatment in familial Mediterranean fever patients: a systematic review and meta-analysis.

OBJECTIVES: FMF is the most common hereditary monogenic fever syndrome marked by recurrent attacks of fever and polyserositis. Colchicine is the current recommended first-line treatment for FMF. However, a small portion of FMF patients are unresponsive or intolerant to colchicine. Anti-IL-1 agents are alternative treatment options for colchicine-resistant or -intolerant FMF patients. This systematic review and meta-analysis aimed to provide qualitative and quantitative evidence for the efficacy and safety of anti-IL-1 agents in adult and paediatric FMF patients. METHODS: MEDLINE, EMBASE, CENTRAL and Web of Science were screened from inception to May 2023. We included adult and paediatric FMF patients who received continuous treatment with at least one of the anti-IL-1 drugs: anakinra, canakinumab and rilonacept. The primary efficacy outcome was the proportion of patients who achieved complete remission of attacks and the primary safety outcome was the proportion of patients who experienced at least one adverse event during treatment. A random-effects meta-analysis was performed for the quantitative synthesis. RESULTS: Fourty-four reports consisting of 1399 FMF patients were included. Sixty percent (95% CI 49%, 72%) of the adult patients and 81% (95% CI 72%, 89%) of the paediatric patients achieved complete remission. Anti-IL-1 agents significantly decreased levels of inflammatory markers. At least one adverse event was observed in 25% (95% CI 13%, 37%) of the adult patients and 12% (95% CI 3%, 21%) of the paediatric patients. CONCLUSION: Anti-IL-1 agents were effective and demonstrated a low adverse event profile in paediatric and adult FMF patients.

Factors triggering familial mediterranean fever attacks, do they really exist?

Several possible factors are hypothesized to trigger familial Mediterranean fever (FMF) attacks; however, there is no consensus on this matter. We aimed to identify these triggering factors and analyze their relationship with the Mediterranean fever gene mutation status. We prepared a questionnaire that included the most commonly mentioned possible trigger factors of familial Mediterranean fever. We administered a questionnaire to 882 patients. We used a questionnaire assessing the following: psychological stress, consumption of tea and coffee, relationship with menses, menopause and post-menopausal alleviation, seasonal changes, traveling for long durations, relocation, starvation, sleeplessness, cold exposure, fatigue, wind exposure, and humidity. The most frequent triggering factor for familial Mediterranean fever attacks was psychological stress (75.2%). Cold exposure was a statistically significant trigger in patients with exon 10 mutations. Humidity was a statistically significant trigger in patients with exon 2 mutations. Seasonal changes, traveling for long durations, relocation, and cold exposure were statistically significant triggers of familial Mediterranean fever attacks in patients with homozygous M694V mutations. Identifying trigger factors can lead to better preventive measures and personalized therapies to decrease familial Mediterranean fever attacks. Patients can significantly decrease the number of familial Mediterranean fever attacks they experience by managing psychological stress and avoiding physical factors such as cold exposure and fatigue. Determining the relationship between trigger factors and patients' Mediterranean fever gene mutation status can lead to personalized therapy for the prevention of familial Mediterranean fever attacks.