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.

Cancer incidence in Familial Mediterranean Fever: A retrospective analysis.

OBJECTIVES: Familial Mediterranean Fever (FMF) is the most common hereditary monogenic fever syndrome that is characterized by recurrent attacks of fever and polyserositis. Anti-inflammatory drugs, with colchicine being the first-line therapy, have been used in the management of FMF. This study aims to evaluate the risk of cancer in Turkish FMF patients. METHODS: We retrospectively screened the cancer-related outcomes of our study group which consisted of Turkish FMF patients registered at our division. Cancer estimates of the Turkish population were published by the Turkish Ministry of Health in the Turkey Cancer Statistics Report 2018. Standardized incidence rates (SIR) were calculated to compare the cancer incidence observed in our study group with the expected cancer incidence of the Turkish population. Subgroup analyses were conducted on the subgroups, based on gender and usage of biological agents. RESULTS: Our study included 1734 FMF patients, 1054 (60.8 %) of whom were females. The total follow-up was 68,784 person-years. Cancer was observed in 35 (2 %) of these patients. Turkish FMF patients had a significantly lower incidence of cancer, compared with the overall Turkish population [SIR 0.64 (95 % CI 0.46-0.89), p < 0.01]. No significant association was found between cancer and biological agent therapies in FMF patients. CONCLUSIONS: Findings from our study indicate that the risk of cancer was decreased by 36 % in Turkish patients with FMF, compared with the outcomes of the overall Turkish population. Life-long exposure to anti-inflammatory drugs, primarily colchicine, may be the underlying reason for this outcome. Further studies are needed for the confirmation and explanation of this association.