The impact of the Eurofever criteria and the new Infevers MEFV classification in real life: results from a large international FMF cohort

Introduction. A classification of genetic variants’ pathogenicity associated to hereditary recurrent fevers and the novel Eurofever/PRINTO classification criteria (EPCC) have been recently developed. Objectives: to evaluate the clinical impact of EPCC criteria and new INSAID pathogenicity classification of MEFV variants in the large international Eurofever FMF cohort. Methods: baseline demographic, genetic and clinical data of FMF patients included in the Eurofever registry were analysed. Genetic and clinical EPCC criteria for FMF were applied. MEFV variants were classified according to the new INSAID classification. Results: Since November 2009, clinical information was available for 1012 FMF (532 males/480 females, 827 children/185 adults) from 119 centres. For 125 patients clinical and genetic data mandatory for the application of EPCC were missing. Among the 887 remaining patients 623 (70.2%) satisfied EPCC (EPPC+), while 264 (29.8%) did not (EPPC-). Most of the EPCC- patients (172, 65.1%) displayed negative or non-informative genetics (monoallelic or biallelic benign variants, monoallelic variant of unknown significance. At baseline, Colchicine was used in most of EPCC+ patients (88%) and in a minor percentage of EPCC- patients (69 %, p < 0.0001), who were treated in a higher proportion with steroid or NSAID on demand (p = 0.003 and 0.008, respectively). Anti-IL-1 treatment was used in 4% of patients. Conclusions: The combination of EPCC and the new classification of genetic variants’ pathogenicity captured the majority of FMF patients in the Eurofever cohort in a homogeneous group. EPPC- patients were characterized by a different phenotype and therapeutic approach.