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
Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.
Autoinflammatory and Autoimmune Diseases (RITA) Center Siena, Azienda Ospedaliero-Universitaria Senese European Reference Network (ERN) for Rare Immunodeficiency, Siena, Italy.
Front Pharmacol. 2025 Feb 19;16:1462254. doi: 10.3389/fphar.2025.1462254. eCollection 2025.
VEXAS 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.
Clinical, laboratory, and therapeutic data from VEXAS patients were obtained from the international AIDA Network VEXAS registry.
In 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.
IL-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.
VEXAS综合征是一种最近发现的全身性自身炎症性疾病，带来了新的诊断和管理挑战。基于对其他自身炎症性疾病的经验，抗白细胞介素（IL）-1、抗IL-6、抗肿瘤坏死因子（TNF）生物技术药物以及Janus激酶抑制剂（JAKis）已广泛应用于VEXAS患者。本研究的目的是利用来自真实世界的数据评估生物技术药物和JAKis的总体有效性和安全性。
VEXAS患者的临床、实验室和治疗数据来自国际AIDA网络VEXAS登记处。
共有69例VEXAS患者纳入本研究。其中，12例患者（13个治疗疗程）接受IL-1抑制剂治疗，12例患者（13个治疗疗程）接受抗IL-6药物治疗，8例患者（9个治疗疗程）接受抗TNF药物治疗，16例患者（17个治疗疗程）接受JAKis治疗。接受抗IL-1药物治疗的3例患者（23%）、接受IL-6抑制剂治疗的2例患者（15%）、接受TNF抑制剂治疗的1例患者（11%）以及接受JAKis治疗的4例患者（23.5%）观察到完全缓解。抗IL-1治疗期间泼尼松（或等效药物）的平均剂量显著降低（p = 0.01），而糖皮质激素在抗IL-6、抗TNF和JAKi治疗期间变化不显著。共有21例患者发生不良事件，其中3例在接受JAKis治疗时导致死亡（肠穿孔、军团病和感染性肺炎）；21例患者中有8例需要停药。
IL-1和IL-6抑制剂以及JAKis是VEXAS患者有前景的治疗选择，尽管必须仔细监测以控制疾病活动并确保安全。
