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

Antonio Vitale^{1

2}, Flavia Leone³, Valeria Caggiano^{1

2}, Andrea Hinojosa-Azaola⁴, Eduardo Martín-Nares⁴, Guillermo Arturo Guaracha-Basañez⁴, Jiram Torres-Ruiz⁴, Perla Ayumi Kawakami-Campos⁵, Pravin Hissaria^{6

7}, Alicia Callisto^{6

7}, Mark Beecher^{6

7}, Lorenzo Dagna^{8

9}, Alessandro Tomelleri^{8

9}, Corrado Campochiaro^{8

9}, Micol Frassi¹⁰, Francesca Crisafulli¹⁰, Franco Franceschini¹⁰, José Hernández-Rodríguez¹¹, Verónica Gómez-Caverzaschi¹¹, Olga Araújo¹¹, Paolo Sfriso¹², Sara Bindoli¹², Chiara Baggio¹², Jessica Sbalchiero^{1

2}, Jurgen Sota^{1

2}, Abdurrahman Tufan¹³, Ibrahim Vasi¹³, Matteo Piga^{14

15}, Alberto Cauli^{14

15}, Maria Antonietta D'Agostino³, Amato De Paulis^{16

17}, Ilaria Mormile¹⁶, Henrique A Mayrink Giardini¹⁸, Rafael Alves Cordeiro¹⁸, Francesco Gavioli^{1

2}, Giuseppe Lopalco¹⁸, Florenzo Iannone¹⁹, Carlomaurizio Montecucco²⁰, Sara Monti²⁰, Guillermo Ruiz-Irastorza^{21

22}, Adriana Soto-Peleteiro^{21

22}, Paola Triggianese^{23

24}, Carmelo Gurnari^{24

25}, Ombretta Viapiana²⁶, Riccardo Bixio²⁶, Rosetta Vitetta²⁷, Edoardo Conticini^{1

2}, Francesco La Torre²⁸, Gaafar Ragab^{29

30}, Ezgi Deniz Batu³¹, Andrés González-García³², Mercedes Peña-Rodríguez³², Monica Bocchia^{2

33}, Ewa Wiesik-Szewczyk³⁴, Karina Jahnz-Rózyk³⁴, Alejandra de-la-Torre³⁵, Alberto Balistreri^{2

36}, Bruno Frediani^{1

2}, Claudia Fabiani^{2

37}, Luca Cantarini^{1

2}

Affiliations

¹ Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.
² Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, Siena, Italy.
³ UOC di Reumatologia, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy.
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, Australia.
⁷ Department of Immunopathology, SA Pathology, Adelaide, Australia.
⁸ 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.
⁹ Università Vita-Salute San Raffaele, Milan, Italy.
¹⁰ Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], 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, University of Padua, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], 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], Department of Internal Medicine and Therapeutics, Università di Pavia, Pavia, Italy.
²¹ Faculty of Medicine and Nursery, University of the Basque Country, UPV/EHU, Biscay, Spain.
²² Autoimmune Diseases Unit, Biocruces Bizkaia Health Research Institute, Biscay, Spain.
²³ Division of Internal Medicine-Hypertension, Department of Medical Sciences, Fondazione PTV Policlinico "Tor Vergata", Rome, Italy.
²⁴ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
²⁵ Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States.
²⁶ Rheumatology Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
²⁷ Unit of Rheumatology, ASL VC Sant' Andrea Hospital, Vercelli, Italy.
²⁸ Department of Pediatrics, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy.
²⁹ Rheumatology and Clinical Immunology Unit, Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt.
³⁰ Faculty of Medicine, Newgiza University, Giza, Egypt.
³¹ Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Türkiye.
³² Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
³³ Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy.
³⁴ 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.
³⁵ Neuroscience Research Group (NEUROS), NeuroVitae Center, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
³⁶ Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
³⁷ Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.

PMID: 40124776
PMCID: PMC11925913
DOI: 10.3389/fphar.2025.1539756

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

Antonio Vitale et al. Front Pharmacol. 2025.

. 2025 Mar 7:16:1539756.

doi: 10.3389/fphar.2025.1539756. eCollection 2025.

Authors

Affiliations

¹ Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, University of Siena, Siena, Italy.
² Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center] Siena, Siena, Italy.
³ UOC di Reumatologia, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy.
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, Australia.
⁷ Department of Immunopathology, SA Pathology, Adelaide, Australia.
⁸ 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.
⁹ Università Vita-Salute San Raffaele, Milan, Italy.
¹⁰ Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], 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, University of Padua, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], 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], Department of Internal Medicine and Therapeutics, Università di Pavia, Pavia, Italy.
²¹ Faculty of Medicine and Nursery, University of the Basque Country, UPV/EHU, Biscay, Spain.
²² Autoimmune Diseases Unit, Biocruces Bizkaia Health Research Institute, Biscay, Spain.
²³ Division of Internal Medicine-Hypertension, Department of Medical Sciences, Fondazione PTV Policlinico "Tor Vergata", Rome, Italy.
²⁴ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
²⁵ Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States.
²⁶ Rheumatology Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
²⁷ Unit of Rheumatology, ASL VC Sant' Andrea Hospital, Vercelli, Italy.
²⁸ Department of Pediatrics, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy.
²⁹ Rheumatology and Clinical Immunology Unit, Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt.
³⁰ Faculty of Medicine, Newgiza University, Giza, Egypt.
³¹ Department of Pediatric Rheumatology, Faculty of Medicine, Hacettepe University, Ankara, Türkiye.
³² Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
³³ Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy.
³⁴ 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.
³⁵ Neuroscience Research Group (NEUROS), NeuroVitae Center, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
³⁶ Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
³⁷ Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.

PMID: 40124776
PMCID: PMC11925913
DOI: 10.3389/fphar.2025.1539756

Abstract

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.

Conclusion: 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.

Keywords: autoinflammatory diseases; cDMARDs; clinical outcomes; diagnosis; treatment.

Copyright © 2025 Vitale, Leone, Caggiano, Hinojosa-Azaola, Martín-Nares, Guaracha-Basañez, Torres-Ruiz, Ayumi Kawakami-Campos, Hissaria, Callisto, Beecher, Dagna, Tomelleri, Campochiaro, Frassi, Crisafulli, Franceschini, Hernández-Rodríguez, Gómez-Caverzaschi, Araújo, Sfriso, Bindoli, Baggio, Sbalchiero, Sota, Tufan, Vasi, Piga, Cauli, D’Agostino, De Paulis, Mormile, Mayrink Giardini, Cordeiro, Gavioli, Lopalco, Iannone, Montecucco, Monti, Ruiz-Irastorza, Soto-Peleteiro, Triggianese, Gurnari, Viapiana, Bixio, Vitetta, Conticini, La Torre, Ragab, Batu, González-García, Peña-Rodríguez, Bocchia, Wiesik-Szewczyk, Jahnz-Rózyk, de-la-Torre, Balistreri, Frediani, Fabiani and Cantarini.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

References

1. Beck D. B., Ferrada M. A., Sikora K. A., Ombrello A. K., Collins J. C., Pei W., et al. (2020). Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N. Engl. J. Med. 383 (27), 2628–2638. 10.1056/NEJMoa2026834 - DOI - PMC - PubMed
1. Bourbon E., Heiblig M., Gerfaud V. M., Barba T., Durel C. A., Lega J. C., et al. (2021). Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 137 (26), 3682–3684. 10.1182/blood.2020010177 - DOI - PubMed
1. Boyadzhieva Z., Ruffer N., Kotter I., Krusche M. (2023). How to treat VEXAS syndrome: a systematic review on effectiveness and safety of current treatment strategies. Rheumatol. Oxf. 62 (11), 3518–3525. 10.1093/rheumatology/kead240 - DOI - PubMed
1. Ferrada M. A., Sikora K. A., Luo Y., Wells K. V., Patel B., Groarke E. M., et al. (2021). Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS. Arthritis Rheumatol. 73 (10), 1886–1895. 10.1002/art.41743 - DOI - PubMed
1. Georgin-Lavialle S., Terrier B., Guedon A. F., Heiblig M., Comont T., Lazaro E., et al. (2022). Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients. Br. J. Dermatol 186 (3), 564–574. 10.1111/bjd.20805 - DOI - PubMed

LinkOut - more resources

Full Text Sources
- Frontiers Media SA
- PubMed Central
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous