Azacitidine Shows Promise in Treating VEXAS Syndrome

Medscape

19-06-2025

Azacitidine showed potential in treating patients with VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, offering high response rates and reducing the use of glucocorticoids. Tocilizumab and anakinra also demonstrated effectiveness, with a higher discontinuation rate seen with the latter.
METHODOLOGY:
Researchers conducted a retrospective cohort study in the UK and analyzed 71 treatment courses in 59 patients with genetically confirmed VEXAS syndrome (mean age at treatment initiation, 71 years; 98% men) across six major tertiary referral centers from July 2014 to October 2024.
Patients received five categories of targeted therapy: Tocilizumab (n = 19), anakinra (n = 13), azacitidine (n = 13), baricitinib (n = 11), and prednisolone alone (n = 10). Data were collected at diagnosis, treatment initiation, and follow-ups at 3 months, 6 months, and 12 months.
Primary outcomes were complete response (defined as clinical remission with a C-reactive protein level ≤ 10 mg/L and requirement of ≤ 10 mg/d prednisolone) and partial response (defined as clinical remission with at least a 50% reduction in both C-reactive protein level and glucocorticoid dose from baseline).
Adverse events and treatment discontinuation were documented, with serious events defined as those requiring permanent discontinuation.
The study followed methods used in a French cohort study with adjustments to only the statistical reporting format to enable comparisons.
TAKEAWAY:
Azacitidine showed a 91% overall response rate at 6 months (10 of 11 patients), with 27% of patients achieving complete response, and maintained effectiveness at 12 months. Glucocorticoid-sparing effects were notable with prednisolone doses reduced to ≤ 5 mg/d in 60% of patients on azacitidine at 12 months.
Anakinra showed promising initial responses at 3 months (seven of eight patients), with a 100% response rate at 6 months in those who tolerated it (n = 3); however, the discontinuation rate was high due to severe injection-site reactions.
Tocilizumab had a 64% response rate at 6 months (seven of 11 patients), with 36% of patients achieving complete response, whereas baricitinib showed modest effectiveness, with the highest mortality at 27%.
Adverse events were documented for 54% of the therapies, with infections being the most common events, particularly noted with azacitidine (62%) and tocilizumab (47%).
IN PRACTICE:
'The findings of this study provide important real-world evidence to guide clinical practice and future research directions in management of patients with VEXAS syndrome,' the authors wrote.
SOURCE:
This study was led by Adam Al-Hakim, BMBS, Leeds Institute for Rheumatic and Musculoskeletal Medicine, Leeds, England. It was published online on May 21, 2025, in The Lancet Rheumatology .
LIMITATIONS:
The sample size was small, which affected the ability to conduct multivariable analyses, thereby affecting the assessment of treatment effectiveness. Clinical response was based on physician opinion, increasing reporting bias and variance. The lack of standardized prednisolone tapering protocols could have influenced response assessments.
DISCLOSURES:
No funding was received for this study. Some authors disclosed receiving honoraria, grants, travel support, and consulting fees from various pharmaceutical companies, including AstraZeneca and Novartis. One author reported receiving support for meetings, projects, advisory boards, and clinical trials from various sources.