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

Marta Bustaffa, Isabelle Koné-Paut, Seza Ozen, Gayane Amaryan, Efimia Papadopoulou-Alataki, Romina Gallizzi, Maria Carrabba, Yonatan Butbul Aviel, Luca Cantarini, Maria Alessio, Jordi Anton, Laura Obici, Faysal Gok, Ezgi Deniz Batu, Estefania Moreno, Paul Brogan, Maria Trachana, Gabriele Simonini, Donato Rigante, Yosef UzielAntonella Insalaco, Maria Cristina Maggio, Nicolino Ruperto, Marco Gattorno, L. Rossi Semerano

Research output: Contribution to journalArticlepeer-review


Introduction: New Eurofever/PRINTO classification criteria (EPCC) for Familial Mediterranean Fever (FMF) and other recurrent fevers have been recently developed, together with the classification of the pathogenicity of MEFV variants. Objectives: To evaluate the impact in real life of both the EPCC and 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 evaluated. The EPCC and the 2018 INSAID classification for MEFV variants were applied in all eligible FMF patients. Results: Since November 2009, clinical information was available for 1012 FMF (532 males/480 females, 827 children/185 adults) from 119 centres. Complete data were available for 887 patients in whom 623 (70.2%) satisfied EPCC (EPCC+), while 264 (29.8%) did not (EPCC−). The majority 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 lower 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). Four percent of patients received Anti-IL-1 treatment. Conclusions: The combination of EPCC and the 2018 INSAID classification of MEFV variants is able to identify two distinct groups of patients, which differ in clinical characteristics, therapeutic approach and response to treatment. EPCC+ patients displayed the typical features of FMF, while EPCC− patients had a more variable phenotype with a lower percentage of response to colchicine.

Original languageEnglish
Article number151957
JournalSeminars in Arthritis and Rheumatism
Publication statusPublished - Feb 2022


  • Autoinflammatory diseases
  • Classification criteria
  • Familial mediterranean fever
  • Genetic analysis
  • Recurrent fevers
  • Registry

ASJC Scopus subject areas

  • Rheumatology
  • Anesthesiology and Pain Medicine


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