Mortality risk factors associated with familial Mediterranean fever among a cohort of 1.25 million adolescents

Gilad Twig, Avi Livneh, Asaf Vivante, Arnon Afek, Ari Shamiss, Estela Derazne, Dorit Tzur, Ilan Ben-Zvi, Amir Tirosh, Micha Barchana, Tamy Shohat, Eliezer Golan, Howard Amital

Research output: Contribution to journalArticlepeer-review


Objective: There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF. Methods: We studied a nationwide, population-based, retrospective cohort of 1225 individuals with FMF (59% men) in a database of 1 244 350 adolescents (16-20 years of age) medically evaluated for military service between 1973 and 1997. This cohort was linked with the national mortality, cancer and end-stage renal disease (ESRD) registries in Israel. Study outcomes were all-cause mortality, occurrence of ESRD and malignancy by the age of 50 years. Results: During 30 years of follow-up, death rates were 8.73/104 versus 4.32/104 person-years in the FMF and control groups, respectively (p=0.002). In a multivariable analysis adjusted for age, birth year, socio-economic status, education, ethnicity and body mass index, FMF was associated with increased mortality in men (HR=1.705 (95% CI 1.059 to 2.745), p=0.028) and women (HR=2.48 (1.032 to 5.992), p=0.042). Renal amyloidosis accounted for 35% and 60% of deaths in men and women, respectively. FMF was not associated with an increased incidence of cancer. Conclusions: FMF is associated with increased all-cause mortality that is likely attributed to reduced colchicine compliance or responsiveness. Individuals with FMF do not have an increased incidence of cancer. These results support the awareness among medical community to decrease the higher than average mortality rate among participants with FMF.

Original languageEnglish
Pages (from-to)704-709
Number of pages6
JournalAnnals of the Rheumatic Diseases
Issue number4
StatePublished - Apr 2014
Externally publishedYes

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • General Biochemistry, Genetics and Molecular Biology


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