Efficacy and safety of conventional disease-modifying antirheumatic drugs in VEXAS syndrome: real-world data from the international AIDA network

• Published in: Frontiers in Pharmacology
• Main Authors: Antonio Vitale, Flavia Leone, Valeria Caggiano, Andrea Hinojosa-Azaola, Eduardo Martín-Nares, Guillermo Arturo Guaracha-Basañez, Jiram Torres-Ruiz, Perla Ayumi Kawakami-Campos, Pravin Hissaria, Alicia Callisto, Mark Beecher, Lorenzo Dagna, Alessandro Tomelleri, Corrado Campochiaro, Micol Frassi, Francesca Crisafulli, Franco Franceschini, José Hernández-Rodríguez, Verónica Gómez-Caverzaschi, Olga Araújo, Paolo Sfriso, Sara Bindoli, Chiara Baggio, Jessica Sbalchiero, Jurgen Sota, Abdurrahman Tufan, Ibrahim Vasi, Matteo Piga, Alberto Cauli, Maria Antonietta D’Agostino, Amato De Paulis, Ilaria Mormile, Henrique A. Mayrink Giardini, Rafael Alves Cordeiro, Francesco Gavioli, Giuseppe Lopalco, Florenzo Iannone, Carlomaurizio Montecucco, Sara Monti, Guillermo Ruiz-Irastorza, Adriana Soto-Peleteiro, Paola Triggianese, Carmelo Gurnari, Ombretta Viapiana, Riccardo Bixio, Rosetta Vitetta, Edoardo Conticini, Francesco La Torre, Gaafar Ragab, Ezgi Deniz Batu, Andrés González-García, Mercedes Peña-Rodríguez, Monica Bocchia, Ewa Wiesik-Szewczyk, Karina Jahnz-Rózyk, Alejandra de-la-Torre, Alberto Balistreri, Bruno Frediani, Claudia Fabiani, Luca Cantarini
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2025-03-01
• Subjects: cDMARDs; clinical outcomes; autoinflammatory diseases; diagnosis; treatment
• Online Access: https://www.frontiersin.org/articles/10.3389/fphar.2025.1539756/full

BackgroundVEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory condition resulting in severe, often treatment-refractory inflammation. Currently, there are no established treatment guidelines for VEXAS syndrome.ObjectivesTo assess the efficacy and safety of conventional disease-modifying antirheumatic drugs (cDMARDs) in a cohort of VEXAS patients.MethodsData from VEXAS patients were obtained from the International AIDA Network VEXAS registry.ResultsData from 36 VEXAS patients were evaluated, with 28 (77.8%) treated with cDMARDs as monotherapy - and concomitant glucocorticoids (GC) - and 8 (22.2%) receiving a combination of different cDMARDs plus GC. Complete response (CR), partial response (PR), and failure to cDMARDs monotherapy were reported in 4/22 (18.2%), 11/22 (50%), and 7/22 (31.8%) courses, respectively. All patients were treated with GCs at the start of cDMARD monotherapy, and no GC discontinuation was observed later. No significant differences were observed in the GC dosage from the start of cDMARDs to the 3-month (p = 0.43), 6-month (p = 0.31), and 12-month (p = 0.21) visits. Conversely, the GC sparing resulted to be statistically significant when using methotrexate (p = 0.02). As for cDMARDs combinations, no cases achieved CR, while PR was observed in 5/9 (55.6%). Seventeen adverse events were reported, seven of which led to discontinuation.ConclusionMany VEXAS patients report a partial benefit from cDMARDs, while a smaller yet not negligible number of patients exhibit a CR; cDMARDs remain a viable option for this disorder, especially when the initial GC dosage is low and the need for a steroid-sparing effect is not immediately urgent.