INSAID variant classification and Eurofever criteria guide optimal treatment strategy in patients with TRAPS: data from the Eurofever registry.

Background TNF receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNFRSF1A gene. Data regarding long-term treatment outcomes is lacking. Objective To assess correlations of genotype-phenotypes in TRAPS patients, 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 INSAID classification in group A (pathogenic or likely pathogenic variants), B (VUS or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria. Results In group A (127/226 patients, 56%), all fulfilled Eurofever criteria and 20/127 patients (16%) developed AA amyloidosis. In group B (78/226 patients, 35%), 40/78 patients (51%) did not fulfill Eurofever criteria, displaying a lower incidence of abdominal pain (p 85% complete response). No patients on anti-IL-1 treatments developed AA amyloidosis and seven women with history of failure to conceive had successful pregnancies. Conclusion Anti-IL-1 drugs are the best maintenance treatment in TRAPS patients. The diagnosis of TRAPS should be considered very carefully in patients of group B not fulfilling Eurofever criteria and C, and colchicine may be preferable as first maintenance treatment.