A study published Tuesday in JAMA revealed VEXAS, a little-known syndrome with a high mortality rate, has a higher prevalence than previously thought.
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A study published Tuesday in JAMA revealed that a little-known syndrome with a high mortality rate has a higher prevalence than previously thought.
VEXAS was first identified in 2020, and patients exhibit unexplained fevers, anemia and inflammation. The lead investigator for the study, David Beck, M.D., Ph.D., also led the team that initially identified the UBA1 gene mutation shared amongst VEXAS patients.
His team utilized that knowledge to screen the blood DNA records of 163,096 consenting patients in the Pennsylvania healthcare system. The UBA1 mutation was found in nine males and two females.
While these figures maintain the disease’s rare status, the previous 2020 findings identified 25 men and zero women in the U.S. with the condition. This new study, led by researchers at NYU Grossman School of Medicine, suggests the rare condition is more vexing than originally thought – 1 in 4,269 men and 1 in 26,238 women, over 50.
Mayo Clinic rheumatologist Matthew Koster, M.D., called the findings “remarkable.”
“Is VEXAS really more common than we think, with patients hiding in plain sight? The answer is yes,” he said.
Proving the greater prevalence in men is of particular importance as that population carries the higher mortality rate. Up to half of people diagnosed with VEXAS, mostly men, die within five years.
The study’s participants lacked diversity – 94% were white and 61% were female, all based in Pennsylvania. The team plans to analyze more racially diverse groups and look for additional genetic causes.
The team said they believe their findings will raise awareness of the disease to increase accurate diagnoses and open avenues for new therapies.
Beck told BioSpace many patients diagnosed with other inflammatory syndromes don’t quite fit the pattern and find treatments ineffective. By testing these subgroups for VEXAS, doctors can target the right treatments for their patients.
The development of a simple blood test for the UBA1 mutation is also on the to-do list to make for an easier, earlier diagnosis.
Current treatments for the disease include high-dose steroids, JANUS kinase inhibitors and, in some qualifying cases, bone marrow transplants to control symptoms. BMT is a curative treatment, as the genetic mutation is in the blood, but one with considerable risk.
The next steps for Beck’s team include a collaboration with the NIH to dig further into the disease drivers, what makes VEXAS more severe in some patients, and how to best treat it.
Beck is hopeful his research efforts will garner some attention from the biopharma field for more treatments, now that they know the disease is more prevalent than previously thought. Being driven by a gene mutation makes the disease a potential target for gene therapy consideration.
