Background: VEXAS syndrome is caused by somatic UBA1 -mutations in the X-chromosome in hematopoietic cells, characterized by dysplasia and inflammatory symptoms [1]. Limited previous data have shown promising results with azacitidine treatment [2].

Objectives: The aim of this study is to evaluate the effectiveness of azacitidine treatment defined in complete and partial response (CR; PR) and the reduction of the lymphocyte corrected variant allele frequency (cVAF) of the UBA1 -mutation in a cohort of patients with VEXAS syndrome.

Methods: Clinical and laboratory data from 21 VEXAS patients were retrospectively evaluated, thirteen were treated with azacitidine (75 mg/m ² QD for seven days every 28 days). Because mature lymphocytes do not contain the UBA1 -mutation, a corrected VAF (cVAF) was calculated.

Results: Of the patients not treated with azacitidine (N=8) no follow-up data is available, due of death, treatment elsewhere or alternative treatment. Ten patients treated with azacitidine showed clear cVAF decreases, all patients had clinical benefit. Four patients achieved CR (cVAFs <1%) with >50% CRP decrease, and no or very low prednisolone dose. Ultimately azacitidine could be stopped successfully. Six patients showed PR, cVAFs decreases ranging from 55-96%, prednisolone could be tapered to 0-7.5 mg QD and four of them showed >50% CRP decrease. Two patients showed little cVAF decreases of 7 and 10%, needing medium doses of prednisolone (10-15 mg QD) with one of them showing >50% CRP decrease.

Conclusion: Azacitidine treatment reduces the cVAF of the UBA1 -mutation, and induces recovery of inflammatory symptoms in most VEXAS patients. If CR is achieved azacitidine can be stopped successfully.

REFERENCES: [1] Beck DB, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med. 2020 Dec 31;383(27):2628-2638.

[2] Aalbers AM, et al. Long-term genetic and clinical remissions after cessation of azacitidine treatment in patients with VEXAS syndrome. Hemasphere. 2024 Jul 30;8(8):e129.

Acknowledgements: NIL.

Disclosure of Interests: Sanne Wijnberger: None declared, Myrthe Natzijl: None declared, Julie Weering: None declared, Jasmijn Meerlo: None declared, Jonas Salzbrunn: None declared, Andre Mulder: None declared, Saskia Klein: None declared, Abraham Rutgers Not related to the data presented.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.