A cross-sectional survey on VEXAS syndrome: insights from a global expert panel

TL;DR

This study surveyed global experts on VEXAS syndrome to understand current diagnostic and treatment practices, revealing a lack of guidelines and highlighting unmet needs.

Contribution

The first global survey on VEXAS syndrome management, capturing real-world practices and identifying key gaps in diagnosis and treatment.

Findings

Most clinicians use UBA1 mutation testing and C-reactive protein to monitor VEXAS syndrome.

Treatment approaches are varied, with corticosteroids and JAK inhibitors commonly used.

Only a minority of clinicians have successfully performed allogeneic stem cell transplants for VEXAS.

Abstract

Vacuolization, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is recently described, for which the diagnosis and management lack official guidelines.

To assess the diagnostic capabilities and disease management of VEXAS syndrome among physicians in the global context.

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.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s10067-025-07617-3.

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