Overall mortality among patients with systemic autoinflammatory diseases in France

Introduction Systemic autoinflammatory diseases (SAIDs) are rare disorders of the innate immune system for which limited data on overall mortality or life expectancy. The aim of this study was to assess overall mortality among patients with familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), TNFR-associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD) in France. Methods Patients with a confirmed diagnosis of FMF, CAPS, TRAPS, or MKD were identified through the French National Rare Disease Registry (BNDMR). Data were contributed by rare disease reference centres within the FAI2R network, following approval by the BNDMR institutional review board. Mortality data were obtained from the BNDMR and supplemented with individual death records from the French National Institute of Statistics and Economic Studies (INSEE). Mortality between January 2010 and December 31 2024 was analysed using age- and sex-specific mortality rates from the Human Mortality Database. Comparative mortality indices (CMIs) were calculated. Results A total of 2010 patients were included between 2010 and 2024: 1647 with FMF, 199 with CAPS, 100 with TRAPS, and 64 with MKD. Estimated prevalence in 2024 was 23.6 per million (95% CI [22.5–24.8]) for FMF, 2.8 per million (95% CI [2.5–3.3]) for CAPS, 1.4 per million (95% CI [1.2–1.7]) for TRAPS, and 0.9 per million (95% CI [0.7–1.2]) for MKD. A total of 36 deaths were observed between 2010 and 2024: 27 among FMF patients, 4 among CAPS patients, 3 among TRAPS patients, and 2 among MKD patients. Over the study period, the comparative mortality index (CMI) was 425 (95% CI [385.55–467.39]), indicating a mortality rate 4.3 times higher than expected compared with the French general population. The lowest CMI was observed in the FMF cohort (385), whereas the highest CMI was observed in the MKD cohort (738). Conclusion These findings highlight a significant public health concern, particularly for the rarest and most difficult-to-treat disease, MKD, but also for FMF, which is the most prevalent SAID. Our results support the need for in-depth analyses of the causes of death to better inform preventive and therapeutic strategies.