Emerging treatment approaches for VEXAS syndrome: a systematic review and meta-analysis.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a monogenic autoinflammatory disorder with significant morbidity and mortality. Numerous treatment options including azacitidine, JAK inhibitors, IL-6 inhibitors, anti-IL-1, and anti-TNF agents have been proposed. However, no consensus on optimal treatment algorithm has been reached. This study aims to evaluate the efficacy and safety of medical treatment options through a meta-analysis of existing data to help establish clearer guidelines for managing VEXAS. The study protocol was registered in PROSPERO (CRD42024590134). MEDLINE and EMBASE were screened from inception until March 2025. We included patients with VEXAS syndrome who received treatment with azacitidine, JAK inhibitors, IL-6 inhibitors, anti-IL-1, or anti-TNF agents. The primary outcome was the proportion of complete responders. Partial response and reported adverse events were also evaluated. A total of 16 studies and 367 patients with VEXAS syndrome were included. Concomitant myelodysplastic syndrome (MDS) was reported in 149 (40.6%) patients. Azacitidine treatment resulted in complete and partial response in 67% [95% CI (0.56,0.77)] and in 73% [95% CI (0.64,0.82)] of cases, respectively. JAK inhibitors produced a complete response in 42% [95% CI (0.33,0.52)] and partial response in 79% [95% CI (0.71,0.87)]. IL-6 inhibitors led to a complete response in 24% [95% CI (0.15,0.32)] and partial response in 72% [95% CI (0.64,0.81)]. Adverse events were frequently observed. Azacitidine demonstrated significant efficacy in patients with MDS. JAK inhibitors and IL-6 inhibitors may also be viable treatment options. Prospective clinical trials are needed for further confirmation of the results.