Azacitidine improves inflammation in 60% of VEXAS patients and induces molecular remission in most tested cases, a new review finds.

The research, published in the British Journal of Haematology [link here], analysed outcomes from 166 patients (median age 71, 98% male) with genetically confirmed VEXAS syndrome treated with hypomethylating agents (HMAs).

Key findings showed 59% of patients achieved an inflammatory response, 74% showed haematological improvement, and 78% of those tested demonstrated molecular remission with a reduction in UBA1 variant allele frequency.

“This review highlights HMAs as a feasible option in the management of VEXAS syndrome,” wrote the authors, including Dr Roochi Trikha, a consultant haematologist at King’s College Hospital NHS Foundation Trust.

Nearly all patients (96%) presented with inflammatory symptoms, most frequently affecting skin (81%). Cytopaenia occurred in 89%, constitutional symptoms in 84%, and 81% had concomitant myelodysplastic syndromes (MDS).

The most common mutations were p.Met41 subsections (81%), with exon 3 splice site mutations the next most prevalent (8%).

Most patients received azacitidine at 75 mg/m² for either 7 days (n=99) or 5 days (n=33) in 28-day cycles.

Among patients taking over 10mg prednisone daily, 52% achieved complete inflammatory response (clinically asymptomatic with prednisone reduced below 10mg daily), while 7% achieved partial response.

For molecular remission, 49 of 63 patients (78%) who underwent post-treatment UBA1 testing showed at least 25% reduction in variant allele frequency, with most (n=32) dropping below 2%.

However, the authors cautioned that “molecular response may be overestimated as patients with clinical improvement could be more likely to undergo repeat UBA1 testing.”

The most common adverse effects included infections, sepsis, cytopenia and pulmonary complications, though the authors noted toxicity data were limited.

The authors suggested HMAs could serve as a bridge to haematopoietic stem cell transplantation, achieving disease control before transplant and potentially reducing post-procedure complications.

They emphasised the review’s limitations, noting VEXAS syndrome is a relatively recent discovery with mainly observational evidence available. Only one prospective phase 2 trial has been completed.

“The heterogeneity of the available data and lack of objective response criteria, as well as the degree of missing or unreported data, did not allow for conducting a meta-analysis,” they added.