AUTHOR=Vitale Antonio , Caggiano Valeria , Leone Flavia , Hinojosa-Azaola Andrea , Martín-Nares Eduardo , Guaracha-Basañez Guillermo Arturo , Torres-Ruiz Jiram , Kawakami-Campos Perla Ayumi , Hissaria Pravin , Callisto Alicia , Beecher Mark , Dagna Lorenzo , Campochiaro Corrado , Tomelleri Alessandro , Frassi Micol , Franceschini Franco , Crisafulli Francesca , Hernández-Rodríguez José , Gómez-Caverzaschi Verónica , Araújo Olga , Sfriso Paolo , Bindoli Sara , Baggio Chiara , Sota Jurgen , Tufan Abdurrahman , Kucuk Hamit , Piga Matteo , Cauli Alberto , D’Agostino Maria Antonietta , De Paulis Amato , Mormile Ilaria , Giardini Henrique A. Mayrink , Cordeiro Rafael Alves , Lopalco Giuseppe , Iannone Florenzo , Monti Sara , Montecucco Carlomaurizio , Ruiz-Irastorza Guillermo , Soto-Peleteiro Adriana , Triggianese Paola , Gurnari Carmelo , Viapiana Ombretta , Bixio Riccardo , Vitetta Rosetta , Rovera Guido , Conticini Edoardo , La Torre Francesco , Portincasa Piero , Jaber Nour , Ragab Gaafar , Maher Amina , Batu Ezgi Deniz , Ozen Seza , Wiesik-Szewczyk Ewa , de-la-Torre Alejandra , Balistreri Alberto , Frediani Bruno , Fabiani Claudia , Cantarini Luca 

TITLE=Efficacy and safety profile of biotechnological agents and Janus kinase inhibitors in VEXAS syndrome: data from the international AIDA Network VEXAS registry

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1462254

DOI=10.3389/fphar.2025.1462254

ISSN=1663-9812

ABSTRACT=BackgroundVEXAS syndrome, a recently identified systemic autoinflammatory disorder, poses new diagnostic and management challenges. Based on experience with other autoinflammatory diseases, anti-interleukin (IL)-1, anti-IL-6, anti-tumor necrosis factor (TNF) biotechnological agents, and Janus kinase inhibitors (JAKis) have been widely employed in VEXAS patients. The aim of this study is to evaluate the global effectiveness and safety of biotechnological agents and JAKis using data from the real-world context.MethodsClinical, laboratory, and therapeutic data from VEXAS patients were obtained from the international AIDA Network VEXAS registry.ResultsIn total, 69 VEXAS patients were enrolled in the study. Among them, 12 patients (13 treatment courses) received IL-1 inhibitors, 12 patients (13 treatment courses) were administered anti-IL-6 agents, 8 patients (9 treatment courses) were treated with anti-TNF agents, and 16 patients (17 treatment courses) were treated with JAKis. A complete response was observed in 3 patients (23%) treated with anti-IL-1 agents, 2 patients (15%) receiving IL-6 inhibitors, 1 patient (11%) receiving TNF inhibitors, and 4 patients (23.5%) treated with JAKis. The mean prednisone (or equivalent) dosage significantly decreased during anti-IL-1 treatment (p = 0.01), while glucocorticoids changed during anti-IL-6, anti-TNF, and JAKi treatment in a non-significant fashion. A total of 21 patients experienced adverse events, 3 of which led to death (gut perforation, Legionnaires’ disease, and infectious pneumonia) while on JAKis; treatment withdrawal was required for 8 out of 21 patients.ConclusionIL-1 and IL-6 inhibitors, along with JAKis, represent promising therapeutic options for VEXAS patients, albeit careful monitoring is mandatory to control disease activity and ensure safety.