Among patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, a newly described disease with overlapping inflammatory and hematologic features, genotype and transfusion dependence are potential predictors of increased mortality risk, according to study results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 5 to 10, 2021.
The newly defined disease, VEXAS, is due to acquired somatic mutations, with missense mutations affecting codon 41 of UBA1 in the majority of cases. The mutations lead to amino acid substitutions of methionine for threonine, valine, or leucine with severe inflammation secondary to reduced translation of the UBA1b isoform and loss of cellular ubiquitylation.
The objective of the current study was to explore the mortality risk and potential predictors of mortality in patients with VEXAS syndrome.
The study included 73 men, aged 40 to 85 years at disease onset, with genetically confirmed VEXAS syndrome. The most common variants at methionine 41 were threonine (n=42), followed by valine (n=16) and leucine (n=11).
The median survival from symptom onset was 10 years, with an overall mortality rate of 27%. The mortality risk was highest among patients with the valine variant (50%), compared with patients with the leucine (18%) or threonine (22%) variant.
Multivariable analysis indicated that the mortality risk was more than 3-fold higher for patients with the valine variant (hazard risk [HR], 3.84; 95% CI, 1.50-9.81; P =.01) and for patients who were transfusion dependent (HR, 3.48; 95% CI, 1.28-9.49; P <.005).
Among patients with a valine vs leucine or threonine amino acid substitution at codon 41, translation of the UBA1b isoform was reduced.
“Given the high mortality rate and lack of effective medical treatments, patients with VEXAS should be considered for bone marrow transplantation, with particular focus on patients with risk factors for increased mortality,” the researchers concluded.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Ferrada M, Savic S, Alessi H, et al. Genotype and transfusion dependence predicts mortality in VEXAS syndrome, a newly described disease with overlap inflammatory and hematologic features. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 1426.
This article originally appeared on Rheumatology Advisor