INSAID Variant Classification and Eurofever Criteria Guide Optimal Treatment Strategy in Patients with TRAPS: Data from the Eurofever Registry

J Allergy Clin Immunol Pract. 2021 Feb;9(2):783-791.e4. doi: 10.1016/j.jaip.2020.10.053. Epub 2020 Nov 9.


Background: TNF receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNF super family receptor 1A (TNFRSF1A) gene. Data regarding long-term treatment outcomes are lacking.

Objective: To assess correlations of genotype-phenotypes in patients with TRAPS, as defined by the International Study Group for Systemic Autoinflammatory Diseases (INSAID) classification and Eurofever criteria, with treatment responses.

Methods: Data from 226 patients with variants of the TNFRSF1A gene and enrolled in the Eurofever registry were classified according to the INSAID classification in groups A (pathogenic or likely pathogenic variants), B (variants of uncertain significance or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria.

Results: In group A (127 of 226 patients, 56%), all fulfilled Eurofever criteria and 20 of 127 patients (16%) developed AA amyloidosis. In group B (78 of 226 patients, 35%), 40 of 78 patients (51%) did not fulfill Eurofever criteria, displaying a lower incidence of abdominal pain (P < .02) and higher efficacy rate of on-demand nonsteroidal anti-inflammatory drugs (P < .02) and colchicine (P < .001). Group C (21 of 226 patients, 9%) presented a milder disease (P < .02) and none fulfilled Eurofever criteria. Anti-IL-1 drugs were the most frequently used in patients fulfilling Eurofever criteria, with the highest efficacy rate (>85% complete response). No patients on anti-IL-1 treatments developed AA amyloidosis, and 7 women with a history of failure to conceive had successful pregnancies.

Conclusion: Anti-IL-1 drugs are the best maintenance treatment in patients with TRAPS. The diagnosis of TRAPS should be considered very carefully in patients of group B not fulfilling Eurofever criteria and group C, and colchicine may be preferable as the first maintenance treatment.

Keywords: AA amyloidosis; Anakinra; Autoinflammatory diseases; Colchicine; TRAPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain
  • Colchicine
  • Female
  • Hereditary Autoinflammatory Diseases* / diagnosis
  • Hereditary Autoinflammatory Diseases* / drug therapy
  • Hereditary Autoinflammatory Diseases* / epidemiology
  • Humans
  • Mutation
  • Registries


  • Colchicine