Geisinger Ventures

NEW YORK, Jan. 24, 2023 /PRNewswire/ -- About 13,200 men and another 2,300 women in the United States over age 50 are estimated to have VEXAS syndrome, according to a new study. Long considered a mystery illness until its genetic basis was identified in 2020, the latest findings, led by researchers at NYU Grossman School of Medicine, offer the first indication of how common the illness is domestically. Although a rare disorder, the syndrome carries a high mortality rate, with up to half of people, mostly men, dying within five years of diagnosis. The syndrome most often involves unexplained fevers and low blood oxygen levels in people diagnosed with other diseases, such as rheumatoid arthritis, lupus, and blood cancer. Some of the symptoms have been linked to an overactive immune system, which can cause inflammation and classifies the syndrome as an autoimmune condition. Researchers say they hope their findings will raise awareness of the disorder among physicians, particularly because high-dose steroids, JANUS kinase inhibitors, and bone marrow transplantation have proven effective in controlling some symptoms. "Now that we know VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians need to add this condition to their list of potential diagnoses when confronted by patients with persistent and unexplained inflammation and low blood cell counts, or anemia," says geneticist and study lead investigator David Beck, MD, PhD. Beck, an assistant professor in the Department of Medicine and the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health, also led the federal research team that initially identified the shared UBA1 mutation among VEXAS patients. In the new study, publishing in the Journal of the American Medical Association (JAMA) online Jan. 24, researchers analyzed the electronic health records of 163,096 mostly white men and women in Pennsylvania who agreed to have their blood DNA screened for signs of genetic disease. Twelve were found to have the UBA1 mutation, with all experiencing VEXAS symptoms. Statistically, this corresponded to one in 4,269 American men over age 50 and one in 26,238 women over age 50 having or are likely to develop the syndrome. This, researchers say, is a higher prevalence figure than many other inflammatory conditions, including vasculitis and myeloid dysplasia syndrome. "Our study offers the first glimpse of just how common VEXAS syndrome is in the United States, particularly among men, who also happen to be the most to die from it," says Beck, who is leading several clinical research efforts into VEXAS syndrome at NYU Langone's Center for Human Genetics and Genomics. Previous research, led by Beck, traced the origins of the syndrome to a mutation, or change in the letter code that makes up DNA, in the gene UBA1 (short for ubiquitin-like modifier activating enzyme 1.) The enzyme usually assists in protein breakdown. VEXAS stands for many of its biological characteristics: vacuoles in blood cells, the E1 enzyme, X-linked, autoinflammatory, and somatic. For the study, researchers analyzed the electronic medical records of adult patients who volunteered to participate in the Geisinger MyCode Community Health Initiative. The program has been collecting data for more than 25 years from patients in Geisinger's 10-plus hospitals in Central and Northeastern Pennsylvania. Almost all study participants who agreed to have their blood DNA tested were white; half were over the age of 60. Beck says the team next plans to analyze patient records in more racially diverse groups, especially among those with higher rates of rheumatologic and blood disease, to gain a more precise picture of who is most at risk of VEXAS syndrome. They also plan to look for additional genetic causes, test new therapies for the syndrome, and develop a simple blood test for UBA1 to make it easier to diagnose. Funding for the study was provided by National Institute of Health grants R00AR078205 and T32GM136542. Besides Beck, other NYU Langone researchers involved in this study are Samuel Magaziner, MPhil; and Ann Cantor, MS. Other study co-investigators are Dale Bodian, PhD, at Geisinger Research in North Bethesda, Md.; Vandan Shah, MD; Uyenlinh Mirshahi, PhD; Natasha Strande PhD; Jeremy Haley, MS; Adam Cook, MS; Wesley Hill; Yi Ding, MD, PhD; and David Carey, PhD, at Geisinger Health in Danville, Pa.; Jung Kim, PhD, and Douglas Stewart, at the National Cancer Institute in Rockville, Md.; Alan Schwartz, MD, PhD, at the University of Washington in St. Louis, Mo.; Peter Grayson, MD, and Marcela Ferrada, MD, at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda; and Daniel Kastner, MD, at the National Human Genome Research Institute, also in Bethesda. Media Inquiries David March Phone: 212-404-3528 [email protected] SOURCE NYU Langone Health

About 13,200 men and another 2,300 women in the United States over age 50 are estimated to have VEXAS syndrome, according to a new study. Long considered a mystery illness until its genetic basis was identified in 2020, the latest findings offer the first indication of how common the illness is domestically. About 13,200 men and another 2,300 women in the United States over age 50 are estimated to have VEXAS syndrome, according to a new study. Long considered a mystery illness until its genetic basis was identified in 2020, the latest findings, led by researchers at NYU Grossman School of Medicine, offer the first indication of how common the illness is domestically. Although a rare disorder, the syndrome carries a high mortality rate, with up to half of people, mostly men, dying within five years of diagnosis. The syndrome most often involves unexplained fevers and low blood oxygen levels in people diagnosed with other diseases, such as rheumatoid arthritis, lupus, and blood cancer. Some of the symptoms have been linked to an overactive immune system, which can cause inflammation and classifies the syndrome as an autoimmune condition. Researchers say they hope their findings will raise awareness of the disorder among physicians, particularly because high-dose steroids, JANUS kinase inhibitors, and bone marrow transplantation have proven effective in controlling some symptoms. "Now that we know VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians need to add this condition to their list of potential diagnoses when confronted by patients with persistent and unexplained inflammation and low blood cell counts, or anemia," says geneticist and study lead investigator David Beck, MD, PhD. Beck, an assistant professor in the Department of Medicine and the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health, also led the federal research team that initially identified the shared UBA1 mutation among VEXAS patients. In the new study, publishing in the Journal of the American Medical Association (JAMA) online Jan. 24, researchers analyzed the electronic health records of 163,096 mostly white men and women in Pennsylvania who agreed to have their blood DNA screened for signs of genetic disease. Twelve were found to have the UBA1 mutation, with all experiencing VEXAS symptoms. Statistically, this corresponded to one in 4,269 American men over age 50 and one in 26,238 women over age 50 having or are likely to develop the syndrome. This, researchers say, is a higher prevalence figure than many other inflammatory conditions, including vasculitis and myeloid dysplasia syndrome. "Our study offers the first glimpse of just how common VEXAS syndrome is in the United States, particularly among men, who also happen to be the most to die from it," says Beck, who is leading several clinical research efforts into VEXAS syndrome at NYU Langone's Center for Human Genetics and Genomics. Previous research, led by Beck, traced the origins of the syndrome to a mutation, or change in the letter code that makes up DNA, in the gene UBA1 (short for ubiquitin-like modifier activating enzyme 1.) The enzyme usually assists in protein breakdown. VEXAS stands for many of its biological characteristics: vacuoles in blood cells, the E1 enzyme, X-linked, autoinflammatory, and somatic. For the study, researchers analyzed the electronic medical records of adult patients who volunteered to participate in the Geisinger MyCode Community Health Initiative. The program has been collecting data for more than 25 years from patients in Geisinger's 10-plus hospitals in Central and Northeastern Pennsylvania. Almost all study participants who agreed to have their blood DNA tested were white; half were over the age of 60. Beck says the team next plans to analyze patient records in more racially diverse groups, especially among those with higher rates of rheumatologic and blood disease, to gain a more precise picture of who is most at risk of VEXAS syndrome. They also plan to look for additional genetic causes, test new therapies for the syndrome, and develop a simple blood test for UBA1 to make it easier to diagnose. Funding for the study was provided by National Institute of Health grants R00AR078205 and T32GM136542. Besides Beck, other NYU Langone researchers involved in this study are Samuel Magaziner, MPhil; and Ann Cantor, MS. Other study co-investigators are Dale Bodian, PhD, at Geisinger Research in North Bethesda, Md.; Vandan Shah, MD; Uyenlinh Mirshahi, PhD; Natasha Strande PhD; Jeremy Haley, MS; Adam Cook, MS; Wesley Hill; Yi Ding, MD, PhD; and David Carey, PhD, at Geisinger Health in Danville, Pa.; Jung Kim, PhD, and Douglas Stewart, at the National Cancer Institute in Rockville, Md.; Alan Schwartz, MD, PhD, at the University of Washington in St. Louis, Mo.; Peter Grayson, MD, and Marcela Ferrada, MD, at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda; and Daniel Kastner, MD, at the National Human Genome Research Institute, also in Bethesda.

If you’re talented enough to locate and make sense of the pricing information that hospitals and payers have been mandated to publish online, you’ll likely find a high degree of variability. The price for a single procedure can often vary by thousands of dollars when you check different insurance carriers. For an example, we’ll look at Geisenger, a 10-hospital health system based in Pennsylvania. Its charge sheet reveals that the gross charge for a platelet-rich plasma injection is about $1,700. For inpatients with Aetna insurance, Geisinger’s flagship medical center charges around $500. But for inpatients with Aetna Better Health insurance, the price is only $193.79. It’s about $715 for inpatients with Cigna’s insurance. Jaewon Ryu, Geisinger’s president and CEO, acknowledged that this picture didn’t seem right on Thursday at Reuters’ Total Health conference in Chicago. To him, the only way this variability can be addressed is by getting decision makers on the payment side of things much more aligned with the care delivery side of things. Because consumers wanted “different flavors of coverage,” insurers responded by launching their own varieties of health plans, Ryu said. But as a consequence, Americans are faced with a degree of variability — which can be problematic because the answer for one person may not be the answer for their neighbor, or sometimes not even the answer for someone living in their own household. “The insurance side of the world, for most patients, is very poorly understood,” Ryu declared. “And I think it’s because the American healthcare system is set up as a fragmented, complicated system, and as a result, people don’t understand. Where did my benefits start? How much do I pay? What is the deductible? How does this apply? There’s a whole slew of questions around just the understanding of insurance coverage.” If you’re managing the health of a population — as is the job for both payers and providers — Ryu argued it’s in your best interest to marry the payment world to the delivery world. “I think we’re in a unique position at Geisinger, because we get to see both sides of this — the payment arm and delivery arm. And when you bring them together, we know that that’s when patients are happiest,” Ryu said, in reference to the work Geisinger has done through its health plan. He pointed out that an important way to decrease variability and increase transparency is through the move to value-based care. Geisinger is not fully integrated into value-based care models — Ryu recognized the health system has one foot in the value-based world and the other in the traditional fee-for-service world. But he said he believes the industry is rightfully moving toward value-based care because these models are easier for patients to understand, and they focus on maintaining patients’ health rather than billing them for different services at alarmingly dissimilar rates. To Ryu, the best example of how providers and payers should be shifting to value-based models is the work that the Centers for Medicare and Medicaid Services has done with the Medicare program to build accountable care organizations. CMS said the Medicare Shared Savings Program saved more than $1.6 billion last year.