Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Vacuolization, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is recently described, for which the diagnosis and management lack official guidelines. AIMS: To assess the diagnostic capabilities and disease management of VEXAS syndrome among physicians in the global context. METHODS: An electronic survey was sent to clinicians with expertise in VEXAS syndrome between January and February 2025 to gather real-life data on the management of VEXAS. RESULTS: Seventy-four clinicians completed the survey from Europe (n = 51, 68.9%), North America (n = 9, 12.2%), Australasia (n = 6, 8.1%), Asia (n = 6, 8.1%), Africa (n = 1, 1.4%), and South America (n = 1, 1.4%), mostly being hematologists (n = 24, 32.4%) and rheumatologists (n = 24, 32.4%). Majority of the clinicians were managing between 1 and 4 (n = 40, 54.1%) and 5 and 9 patients (n = 17, 23%) with VEXAS syndrome, with regular clinic review, typically under 7-weekly intervals (n = 44, 59.5%). UBA1 mutation testing was available for 76% of physicians and next-generation sequencing (NGS) of the entire gene was most common (n = 24, 32.9%) with a turnaround time within 12 weeks. C-reactive protein (CRP) was selected by over half of the clinicians (n = 35, 55.4%) as a marker of disease relapse. Treatment with corticosteroids at 1 mg/kg (n = 48, 64.9%) was the most common initial dosing and upfront systemic immunomodulatory treatment was added by more than half of clinicians (n = 39, 52.7%). The most frequent treatments of choice (n = 66) were Janus kinase inhibitors (JAKi) and IL-6 targeted monoclonal antibodies (both n = 21, 31.8%). Azacitidine was mostly used in patients with concomitant myelodysplastic syndrome (MDS) (69.9%). Only 29.6% indicated that allogeneic hematopoietic stem cell transplant (allo-HSCT) had been successfully completed in their department. CONCLUSIONS: This is the first clinician survey on VEXAS syndrome, encompassing a global representation of multiple specialties on current disease management, highlighting several unmet needs (longitudinal follow-up, lack of on-label drugs, financial toxicity) actionable for future research. Keypoints • Globally, VEXAS syndrome is being increasingly recognized, and this survey demonstrates real-life physician practices. • The survey identified both hematologists and rheumatologists as the main care providers, amongst other specialties, identifying the need for a multidisciplinary approach in managing patients with VEXAS syndrome. • Diagnostic UBA1 testing was available for more than 75% clinicians with turnaround time < 12 weeks and C-reactive protein was selected as a useful marker of disease relapse. • Treatment modalities were heterogeneous, identifying the need for consensus guidelines.
Source: Clinical Rheumatology
Authors: Syed B. Ali, Carmelo Gurnari
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,890
Funder: Flinders University
OpenAlex ID: W4413056099