Open Access

Frontiers in Pharmacology

, volume 16

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

Antonio Vitale ^{1, 2}

Valeria Caggiano ^{1, 2}

Flavia Leone ³

Andrea Hinojosa-Azaola ⁴

Eduardo Martín-Nares ⁴

Guillermo Arturo Guaracha-Basañez ⁴

Jiram Torres-Ruiz ⁴

Perla Ayumi Kawakami‐Campos ⁵

Pravin Hissaria ^{6, 7}

Alicia Callisto ^{6, 7}

Mark Beecher ^{6, 7}

Lorenzo Dagna ^{8, 9}

Corrado Campochiaro ^{8, 9}

Alessandro Tomelleri ^{8, 9}

Micol Frassi ¹⁰

Franco Franceschini ¹⁰

Francesca Crisafulli ¹⁰

José Hernández-Rodríguez ¹¹

Verónica Gómez-Caverzaschi ¹¹

Olga Araújo ¹¹

Paolo Sfriso ¹²

Sara Bindoli ¹²

Chiara Baggio ¹²

Jurgen Sota ^{1, 2}

Abdurrahman Tufan ¹³

Hamit Kucuk ¹³

Matteo Piga ^{14, 15}

Alberto Cauli ^{14, 15}

Maria Antonietta D’Agostino ³

Amato de Paulis ^{16, 17}

Ilaria Mormile ¹⁶

Henrique A Mayrink Giardini ¹⁸

Rafael Alves Cordeiro ¹⁸

Giuseppe Lopalco ¹⁹

Florenzo Iannone ¹⁹

Sara Monti ^{20, 21}

Carlomaurizio Montecucco ^{20, 21}

Guillermo Ruiz-Irastorza ^{22, 23}

Adriana Soto-Peleteiro ^{22, 23}

Paola Triggianese ^{24, 25}

Carmelo Gurnari ^{26, 27}

Ombretta Viapiana ²⁸

Riccardo Bixio ²⁸

Rosetta Vitetta ²⁹

Guido Rovera ²⁹

Edoardo Conticini ^{1, 2}

Francesco La Torre ³⁰

Piero Portincasa ³¹

Nour Jaber ³¹

Gaafar Ragab ^{32, 33}

Amina Maher ^{32, 33}

Ezgi Deniz Batu ³⁴

Seza Ozen ³⁴

Ewa Wiesik-Szewczyk ³⁵

Alejandra de-la-Torre ³⁶

Alberto Balistreri ^{4, 37}

Bruno Frediani ^{1, 2}

Claudia Fabiani ^{2, 38}

Luca Cantarini ^{1, 2}

Hide authors affiliations Show authors affiliations: 38 affiliations

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 |

UOC di Reumatologia, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy

Istituti di Ricovero e Cura a Carattere Scientifico

Università Cattolica del Sacro Cuore

⁴

Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico city, Mexico |

⁵

Department of Ophthalmology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico |

⁶

Department of Clinical Immunology and Allergy, Royal Adelaide Hospital, Adelaide, SA, Australia |

⁷

Department of Immunopathology, SA Pathology, Adelaide, SA, Australia |

⁸

Division of Immunology, Transplants and Infectious Diseases, Università Vita-Salute San Raffaele, Milan, Italy |

⁹

Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS Ospedale San Raffaele, European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center, Milan, Italy |

¹⁰

Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center, University of Brescia, Brescia, Italy |

¹¹

Clinical Unit of Autoinflammatory Diseases, Department of Autoimmune Diseases, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic of Barcelona, European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center, University of Barcelona, Barcelona, Spain |

¹²

Rheumatology Unit, Department of Medicine, European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center, University of Padua, Padua, Italy |

¹³

Department of Internal Medicine, Division of Rheumatology, Gazi University Hospital, Ankara, Türkiye |

¹⁴

Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy |

¹⁵

Rheumatology Unit, AOU Cagliari, Cagliari, Italy |

¹⁶

Department of Translational Medical Sciences, Section of Clinical Immunology, University of Naples Federico II, Naples, Italy |

¹⁷

Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, Italy |

¹⁸

Rheumatology Division, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, Brazil |

¹⁹

Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) Policlinic Hospital, University of Bari, Bari, Italy |

²⁰

Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center, Pavia, Italy |

²¹

Department of Internal Medicine and Therapeutics, Università di, Pavia, Italy |

²²

Faculty of Medicine and Nursery, University of the Basque Country, UPV/EHU, Leioa, Biscay, Spain |

²³

Autoimmune Diseases Unit, Biocruces Bizkaia Health Research Institute, Barakaldo, Biscay, Spain |

²⁴

Rheumatology, Allergology and Clinical Immunology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy |

²⁵

Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy |

²⁶

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy |

²⁷

Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States |

²⁸

Rheumatology Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy |

²⁹

Unit of Rheumatology, ASL VC Sant’ Andrea Hospital, Vercelli, Italy |

³⁰

Department of Pediatrics, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy |

³¹

Clinica Medica “A. Murri”, Division of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy |

³²

Rheumatology and Clinical Immunology Unit, Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt |

³³

Faculty of Medicine, Newgiza University, 6th of October City, Egypt |

³⁴

Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Türkiye |

³⁵

Department of Internal Medicine, Pneumonology, Allergology and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, National Research Institute, Warsaw, Poland |

³⁶

Neuroscience Research Group (NEUROS), NeuroVitae Center, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia |

³⁷

Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy |

³⁸

Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy |

Publication type: Journal Article

Publication date: 2025-02-19

Frontiers Media S.A.

Frontiers in Pharmacology

scimago Q1

wos Q1

SJR: 1.220

CiteScore: 8.9

Impact factor: 4.8

ISSN: 16639812

DOI: 10.3389/fphar.2025.1462254

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Abstract

Background

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.

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 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.

Conclusion

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.

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Vitale A. et al. Efficacy and safety profile of biotechnological agents and Janus kinase inhibitors in VEXAS syndrome: data from the international AIDA Network VEXAS registry // Frontiers in Pharmacology. 2025. Vol. 16.

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@article{2025_Vitale,

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

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},

year = {2025},

volume = {16},

publisher = {Frontiers Media S.A.},

month = {feb},

url = {https://www.frontiersin.org/articles/10.3389/fphar.2025.1462254/full},

doi = {10.3389/fphar.2025.1462254}

}

Publisher

Frontiers Media S.A.

Journal

Frontiers in Pharmacology

scimago Q1

wos Q1

SJR

1.220

CiteScore

8.9

Impact factor

4.8

ISSN

16639812 (Print, Electronic)