A new study presented this week at the American College of Rheumatology’s annual meeting, ACR Convergence, found a relationship between genotype, bone marrow failure, and survival in patients with the rare autoinflammatory disease VEXAS syndrome, confirmed only in 2020. is showing.
VEXAS, an acronym for vacuole, E1 enzyme, X-chain, autoinflammatory and somatic syndrome, is a newly defined adult-onset genetic disorder. This usually affects men. VEXAS is caused by mutations in the UBA1 gene that cause ubiquitin activating enzymes. VEXAS causes inflamed bone marrow blood cells and a variety of clinical symptoms similar to other diseases.
This new study provides important clues for predicting survival and mortality in people with VEXAS syndrome. These previously undefined factors could guide physicians in managing patients with this new illness.
“Our interest in conducting this study was driven by the high mortality rate seen in these patients with VEXAS syndrome. To understand the natural history of the disease and guide administrative decisions. We wanted to identify the clinical features that predict survival, “says Marcela A. Ferrada. , MD, Lawrence Schulman scholar and research co-author of the National Institute for Arthritis and Musculoskeletal and Skin Diseases (NIAMS). “To understand the progression, complications, and most importantly, better ways of caring for and treating patients with VEXAS syndrome, we need to know more about VEXAS syndrome. At this time, managing VEXAS patients is a disease. It is greatly influenced by the stage. At the stage of illness, the patient suffers from inflammation. At the later stage, problems related to myelopathy tend to occur. “
The study included 73 patients with VEXAS genetically identified based on disease-related mutations in the UBA1 gene. The median age of onset was 66 years, and the age of patients ranged from 40 to 85 years. All were Caucasian men and were treated with glucocorticoids. Misdiagnosed as other disorders, including 53% of relapsing polychondritis, 35% of myelodysplastic syndrome, and 20% of sweet syndrome, before genetic testing confirms that the patient has VEXAS. Was there.
The researchers estimated the median survival of patients and compared the differences in survival by genotype. They also identified the association between patient clinical characteristics such as the age of onset, thromboembolic disease, and pulmonary infiltrate with transfusion dependence, genotype, and mortality. They also studied the association between genetic variation in patients and UBA1b isoform expression.
Overall, they found a patient mortality rate of 27%. The median age of survival from the onset of symptoms was 10 years. Deaths were more common in 50% of patients studying valine gene variants, compared to 18% of leucine patients and 22% of threonine variants, respectively. Patients with the valine mutant had a median survival of 9 years, which was significantly shorter than patients with the other mutants. Researchers also found two independent predictors of mortality: both having a valine variant and becoming transfusion-dependent increased the risk of death in VEXAS patients. Other clinical features were not associated with mortality.
Given the high mortality rate and the current lack of effective treatments for VEXAS syndrome, the authors of the study suggest that these patients should consider bone marrow transplantation, especially if there are other life-threatening risk factors. thinking about.
“Knowing certain survival-related variables can help determine which patients with VEXAS syndrome will benefit from early and aggressive intervention. This is to make those decisions. It also helps you learn the parameters you need to follow, “says Dr. Ferrada. “This study provides important information that is likely to be used to inform treatment decisions for VEXAS patients, such as when and who to consider. Bone marrow Transplant. ”