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

Antonio Vitale ¹ Flavia Leone ² Valeria Caggiano ¹ Andrea Hinojosa-Azaola ³ Eduardo Martin-Nares ³ Guillermo Arturo Guaracha-Basañez ³ José Jiram Torres-Ruiz ³ Perla Ayumi Kawakami- Campos ³ Pravin Hissaria ⁴ Alicia Callisto ⁴ Mark Beecher ⁴ Lorenzo Dagna ⁵ Alessandro Tomelleri ⁵ Corrado Campochiaro ⁵ Micol Frassi ⁶ Francesca Crisafulli ⁶ Franco Franceschini ⁶ José Hernández-Rodríguez ⁷ Veronica Gomez-Caverzaschi ⁷ Olga Araújo ⁷ Paolo Sfriso ⁸ Sara Bindoli ⁸ Chiara Baggio ⁸ Jessica Sbalchiero ¹ Jurgen Sota ¹ Abdurrahman Tufan ⁹ İbrahim Vasi ⁹ Matteo Piga ¹⁰ Alberto Cauli ¹⁰ Maria Antonietta D'Agostino ² Amato De Paulis ¹¹ Ilaria Mormile ¹¹ Henrique Giardini ¹² Rafael Alves Cordeiro ¹² Francesco Gavioli ¹ Giuseppe Lopalco ¹³ Florenzo Iannone ¹³ Carlomaurizio Montecucco ¹⁴ Sara Monti ¹⁴ Guillermo Ruiz-Irastorza ¹⁵ Adriana Soto Peleteiro ¹⁵ Paola Triggianese ¹⁶ Carmelo Gurnari ¹⁷ Ombretta Viapiana ¹⁸ Riccardo Bixio ¹⁸ Rosetta Vitetta ¹⁹ Edoardo Conticini ¹ Francesco La Torre ¹³ Gaafar Ragab ²⁰ Ezgi Deniz Batu ²¹ Andrés González-García ²² Mercedes Peña Rodríguez ²² Monica Bocchia ¹ Ewa Barbara Wiesik-Szewczyk ²³ Karina Jahnz-Różyk ²³ Alejandra de-la-Torre ²⁴ Alberto Balistreri ¹ Bruno Frediani ¹ Claudia Fabiani ¹ Luca Cantarini ^1*

• ¹ University of Siena, Siena, Tuscany, Italy
• ² Catholic University of the Sacred Heart, Rome, Rome, Sicily, Italy
• ³ National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, México, Mexico
• ⁴ Royal Adelaide Hospital, Adelaide, South Australia, Australia
• ⁵ San Raffaele Hospital (IRCCS), Milan, Lombardy, Italy
• ⁶ University of Brescia, Brescia, Lombardy, Italy
• ⁷ Hospital Clinic of Barcelona, Barcelona, Catalonia, Spain
• ⁸ University of Padua, Padua, Veneto, Italy
• ⁹ Gazi University, Ankara, Ankara, Türkiye
• ¹⁰ University of Cagliari, Cagliari, Sardinia, Italy
• ¹¹ Federico II University Hospital, Naples, Campania, Italy
• ¹² University of São Paulo, São Paulo, Rio Grande do Sul, Brazil
• ¹³ University of Bari Aldo Moro, Bari, Italy
• ¹⁴ University of Pavia, Pavia, Lombardy, Italy
• ¹⁵ University of the Basque Country, Bilbao, Basque Country, Spain
• ¹⁶ Policlinico Tor Vergata, Rome, Lazio, Italy
• ¹⁷ University of Rome Tor Vergata, Roma, Lazio, Italy
• ¹⁸ University of Verona, Verona, Veneto, Italy
• ¹⁹ Azienda Sanitaria Locale Vercelli, Vercelli, Piedmont, Italy
• ²⁰ Cairo University, Giza, Giza, Egypt
• ²¹ Hacettepe University, Ankara, Ankara, Türkiye
• ²² Ramón y Cajal University Hospital, Madrid, Madrid, Spain
• ²³ University of Warsaw, Warsaw, Masovian, Poland
• ²⁴ Universidad del Rosario, Bogotá, Cundinamarca, Colombia

Background: VEXAS (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. Objectives: To assess the efficacy and safety of conventional disease-modifying antirheumatic drugs (cDMARDs) in a cohort of VEXAS patients. Methods: Data from VEXAS patients were obtained from the International AIDA Network VEXAS registry. Results: Data 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. Conclusions: many 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.