TY - JOUR
T1 - INSAID Variant Classification and Eurofever Criteria Guide Optimal Treatment Strategy in Patients with TRAPS
T2 - Data from the Eurofever Registry
AU - Pediatric Rheumatology International Trials Organization (PRINTO) the EUROTRAPS, and the Eurofever Project
AU - Papa, Riccardo
AU - Lane, Thirusha
AU - Minden, Kirsten
AU - Touitou, Isabelle
AU - Cantarini, Luca
AU - Cattalini, Marco
AU - Obici, Laura
AU - Jansson, Annette F.
AU - Belot, Alexandre
AU - Frenkel, Joost
AU - Anton, Jordi
AU - Wolska-Kusnierz, Beata
AU - Berendes, Rainer
AU - Remesal, Agustin
AU - Jelusic, Marija
AU - Hoppenreijs, Esther
AU - Espada, Graciela
AU - Nikishina, Irina
AU - Maggio, Maria Cristina
AU - Bovis, Francesca
AU - Masini, Marta
AU - Youngstein, Taryn
AU - Rezk, Tamer
AU - Papadopoulou, Charalampia
AU - Brogan, Paul A.
AU - Hawkins, Philip N.
AU - Woo, Patricia
AU - Ruperto, Nicolino
AU - Gattorno, Marco
AU - Lachmann, Helen J.
N1 - Funding Information: Unrestricted research grants to Eurofever were kindly provided by Sobi and Novartis . The project has been supported by E-Rare-3 project (INSAID, grant 003037603 ), Executive Agency for Health and Consumers of the European Union (EAHC, Projects 2007332 and 200923 ; https://www.printo.it/eurofever/index.asp ), and by Coordination Theme 1 (Health) of the European Community's FP7 (grant agreement HEALTH-F2-2008-200923 ; https://cordis.europa.eu/project/id/200923 ). Several authors of this publication are members of the European Reference Network for Rare Immunodeficiency, Autoinflammatory, and Autoimmune Diseases (ERN RITA, Project ID No 739543; http://rita.ern-net.eu/ ). Unrestricted educational grants were also kindly provided by PRINTO and Novartis . The abstract of the present study has been presented at the Federation of Clinical Immunology Societies (FOCIS) 2020 Annual Meeting in San Francisco, California (abstract ID 820646). Publisher Copyright: © 2020 American Academy of Allergy, Asthma & Immunology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - AA amyloidosis
KW - Anakinra
KW - Autoinflammatory diseases
KW - Colchicine
KW - TRAPS
U2 - 10.1016/j.jaip.2020.10.053
DO - 10.1016/j.jaip.2020.10.053
M3 - Article
SN - 2213-2198
SP - 783
EP - 791
JO - J. Allergy Clin. Immunol. Pract.
JF - J. Allergy Clin. Immunol. Pract.
ER -