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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1462254

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

Provisionally accepted
Antonio Vitale Antonio Vitale 1Valeria Caggiano Valeria Caggiano 1Flavia Leone Flavia Leone 2Andrea Hinojosa-Azaola Andrea Hinojosa-Azaola 3Eduardo Martin-Nares Eduardo Martin-Nares 3Guillermo Arturo Guaracha-Basañez Guillermo Arturo Guaracha-Basañez 3Jiram Torres-Ruiz Jiram Torres-Ruiz 3Perla Ayumi Kawakami-Campos Perla Ayumi Kawakami-Campos 3Pravin Hissaria Pravin Hissaria 4Alicia Callisto Alicia Callisto 4Mark Beecher Mark Beecher 4Lorenzo Dagna Lorenzo Dagna 5Corrado Campochiaro Corrado Campochiaro 5Alessandro Tomelleri Alessandro Tomelleri 5Micol Frassi Micol Frassi 6Franco Franceschini Franco Franceschini 6Francesca Crisafulli Francesca Crisafulli 6José Hernández-Rodríguez José Hernández-Rodríguez 7Veronica Gomez-Caverzaschi Veronica Gomez-Caverzaschi 7Olga Araújo Olga Araújo 7Paolo Sfriso Paolo Sfriso 8Sara Bindoli Sara Bindoli 8Chiara Baggio Chiara Baggio 8Jurgen Sota Jurgen Sota 1Abdurrahman Tufan Abdurrahman Tufan 9Hamit Kucuk Hamit Kucuk 9Matteo Piga Matteo Piga 10Alberto Cauli Alberto Cauli 10Maria Antonietta D'Agostino Maria Antonietta D'Agostino 11Amato De Paulis Amato De Paulis 12Ilaria Mormile Ilaria Mormile 13Henrique Giardini Henrique Giardini 14Rafael Alves Cordeiro Rafael Alves Cordeiro 14Giuseppe Lopalco Giuseppe Lopalco 15Florenzo Iannone Florenzo Iannone 15Sara Monti Sara Monti 16Carlomaurizio Montecucco Carlomaurizio Montecucco 16Guillermo Ruiz-Irastorza Guillermo Ruiz-Irastorza 17Adriana Soto- Peleteiro Adriana Soto- Peleteiro 17Paola Triggianese Paola Triggianese 18Carmelo Gurnari Carmelo Gurnari 18Ombretta Viapiana Ombretta Viapiana 19Riccardo Bixio Riccardo Bixio 19Rosetta Vitetta Rosetta Vitetta 20Guido Rovera Guido Rovera 20Edoardo Conticini Edoardo Conticini 1Francesco La Torre Francesco La Torre 15Piero Portincasa Piero Portincasa 15Nour Jaber Nour Jaber 15Gaafar Ragab Gaafar Ragab 21Amina Maher Amina Maher 21Ezgi Deniz Batu Ezgi Deniz Batu 22Seza Ozen Seza Ozen 22Ewa Wiesik-Szewczyk Ewa Wiesik-Szewczyk 23Alejandra De-La- Torre Alejandra De-La- Torre 24Alberto Balistreri Alberto Balistreri 1Bruno Frediani Bruno Frediani 1Claudia Fabiani Claudia Fabiani 1Luca Cantarini Luca Cantarini 1*
  • 1 University of Siena, Siena, Italy
  • 2 Catholic University of the Sacred Heart, Rome, Rome, Sicily, Italy
  • 3 Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexico City, Mexico
  • 4 Royal Adelaide Hospital, Adelaide, South Australia, Australia
  • 5 Vita-Salute San Raffaele University, Milan, Lombardy, Italy
  • 6 University of Brescia, Brescia, Lombardy, Italy
  • 7 University 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 Agostino Gemelli University Policlinic, Rome, Lazio, Italy
  • 12 University of Naples Federico II, Naples, Campania, Italy
  • 13 Federico II University Hospital, Naples, Campania, Italy
  • 14 University of São Paulo, São Paulo, Rio Grande do Sul, Brazil
  • 15 University of Bari Aldo Moro, Bari, Italy
  • 16 University of Pavia, Pavia, Lombardy, Italy
  • 17 Biocruces Bizkaia Health Research Institute, Barakaldo, Spain
  • 18 University of Rome Tor Vergata, Roma, Lazio, Italy
  • 19 University of Verona, Verona, Veneto, Italy
  • 20 Ospedaliero S. Andrea Vercelli, Vercelli, Piedmont, Italy
  • 21 Cairo University, Giza, Giza, Egypt
  • 22 Hacettepe University Hospital, Ankara, Ankara, Türkiye
  • 23 Department of Internal Medicine, Pulmonology, Allergy and Clinical Immunology, Military Institute of Medicine (Poland), Warsaw, Masovian, Poland
  • 24 Rosario University, Bogotá, Bogota, Colombia

The final, formatted version of the article will be published soon.

    Background: VEXAS syndrome, a recently identified systemic autoinflammatory disorder, represents a newly diagnostic and management challenge. Based on experience with other autoinflammatory diseases, anti-interleukin (IL)-1, anti-IL-6, anti-tumor necrosis factor (TNF) biotechnological agents and Janus kinases inhibitors (JAKi) have been largely employed in VEXAS patients. The aim of this study is to evaluate the global effectiveness and safety of biotechnological agents and JAKi drawing data from the real-world context. Methods: Clinical, laboratory and therapeutic data from VEXAS patients were obtained from the international AIDA Network VEXAS registry. Results: In total, 69 VEXAS patients were enrolled. Twelve patients (13 treatment courses) underwent IL-1 inhibitors, 12 (13 treatment courses) were administered anti-IL-6 agents, 8 patients (9 treatment courses) were treated with anti-TNF agents and 16 (17 treatment courses) with JAKi. A complete response was observed in 3 (23%) patients treated with anti-IL-1 agents, 2 (15%) patients undergoing IL-6 inhibitors, 1 (11%) patient administered TNF inhibitors, and 4 (23.5%) while on JAKi. 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, three of which led to death (gut perforation, Legionnaires' disease, infectious pneumonia) while on JAKi; 8/21 patients required treatment withdrawal. Conclusions: IL-1 and IL-6 inhibitors, along with JAKi, represent an opportunity for VEXAS patients, albeit careful monitoring is mandatory to control disease activity and safety.

    Keywords: Anti-TNF, anakinra, Canakinumab, JAK inhibitors, tocilizumab, Treatment

    Received: 09 Jul 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Vitale, Caggiano, Leone, Hinojosa-Azaola, Martin-Nares, Guaracha-Basañez, Torres-Ruiz, Kawakami-Campos, Hissaria, Callisto, Beecher, Dagna, Campochiaro, Tomelleri, Frassi, Franceschini, Crisafulli, Hernández-Rodríguez, Gomez-Caverzaschi, Araújo, Sfriso, Bindoli, Baggio, Sota, Tufan, Kucuk, Piga, Cauli, D'Agostino, De Paulis, Mormile, Giardini, Cordeiro, Lopalco, Iannone, Monti, Montecucco, Ruiz-Irastorza, Soto- Peleteiro, Triggianese, Gurnari, Viapiana, Bixio, Vitetta, Rovera, Conticini, La Torre, Portincasa, Jaber, Ragab, Maher, Batu, Ozen, Wiesik-Szewczyk, De-La- Torre, Balistreri, Frediani, Fabiani and Cantarini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Luca Cantarini, University of Siena, Siena, Italy

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