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

and the Eurofever Project Pediatric Rheumatology International Trials Organization (PRINTO) the EUROTRAPS, Riccardo Papa, Thirusha Lane, Kirsten Minden, Isabelle Touitou, Luca Cantarini, Marco Cattalini, Laura Obici, Annette F. Jansson, Alexandre Belot, Joost Frenkel, Jordi Anton, Beata Wolska-Kusnierz, Rainer Berendes, Agustin Remesal, Marija Jelusic, Esther Hoppenreijs, Graciela Espada, Irina Nikishina, Maria Cristina MaggioFrancesca Bovis, Marta Masini, Taryn Youngstein, Tamer Rezk, Charalampia Papadopoulou, Paul A. Brogan, Philip N. Hawkins, Patricia Woo, Nicolino Ruperto, Marco Gattorno, Helen J. Lachmann

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)783-791
Number of pages9
JournalJ. Allergy Clin. Immunol. Pract.
Publication statusPublished - 2021


  • AA amyloidosis
  • Anakinra
  • Autoinflammatory diseases
  • Colchicine


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