Recurrent fever and association with severe organ involvement, mortality and treatment outcomes in VEXAS syndrome: data from the AIDA Network

Caggiano V.;Sbalchiero J.;Frassi M.;Crisafulli F.;Cavazzana I.;Hinojosa-Azaola A.;Martin-Nares E.;Guaracha-Basanez G. A.;Torres-Ruiz J.;Wiesik-Szewczyk E.;Nowakowska-Plaza A.;Sfriso P.;Bindoli S.;Rizzo S.;Hernandez-Rodriguez J.;Gomez-Caverzaschi V.;Araujo O.;Mayrink Giardini H. A.;Gonzalez-Garcia A.;Lopalco G.;Viapiana O.;Bixio R.;Tufan A.;Hissaria P.;Beecher M.;Callisto A.;De Paulis A.;Dagna L.;Campochiaro C.;Tomelleri A.;Bugatti S.;Milanesi A.;Ruiz-Irastorza G.;Soto-Peleteiro A.;Piga M.;Cauli A.;Conti F.;Cardamone C.;Triggianese P.;Gurnari C.;Vitetta R.;Prete M.;Racanelli V.;Talarico R.;Ferro F.;di Cianni F.;Cuccaro M. C.;Mayo-Juanatey A.;Renieri A.;Sorrentino V.;Ergun M. A.;Balistreri A.;Frediani B.;Bocchia M.;Fabiani C.;Cantarini L.;Vitale A.

2026-01-01

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Abstract

Introduction: Recurrent febrile episodes account for one of the most frequent symptoms observed in Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome and a key target for therapeutic intervention. Therefore, this study aims at investigating the association between recurrent febrile episodes and specific clinical manifestations, mortality and response to treatment. Methods: Data were obtained from the international AutoInflammatory Disease Alliance (AIDA) Network registry and analyzed using a Bayesian statistical approach. Posterior probabilities [P(β)] were calculated to assess the likelihood that fever was associated with clinical, laboratory, genetic, and therapeutic features. Results: In total, 87 VEXAS patients were enrolled, 65 (74.7%) of whom suffered from recurrent fever episodes. Fever episodes showed a significant association with patients’ mortality [P(β): 99.41%], as well as with major inflammatory organ involvement, including cardiac [P(β): 99.99%], lung [P(β): 99.98%], and gastrointestinal [P(β): 97.5%] involvement. The occurrence of recurrent fever episodes was associated with a negligible probability of both complete response and treatment failure [P(β) <2.5%], instead favoring a partial response [P(β) >97.5%] to conventional disease modifying anti-rheumatic drugs, Janus Kinases inhibitors, and tocilizumab. For temperatures exceeding 40 °C, using anti-interleukin-1 agents was associated with a high probability of treatment failure [P(β): 99.3%]. Conclusions: febrile episodes are associated with more severe pattern of organ involvement and, accordingly, to death. Furthermore, febrile episodes could correlate with differential therapeutic responsiveness, thereby potentially serving as a valuable marker to guide the treatment strategies in VEXAS patients.