Development of a Disease Activity Index for the Assessment of VEXAS Syndrome (VEXAS-DAI)

Kevin Byram¹, Herman Mann², Danielle Hammond³, Sinisa Savic⁴, Yohei Kirino⁵, Carmelo Gurnari⁶, Mael Heiblig⁷, Thibault Comont⁸, Arsène Mekinian⁹, Mrinal Patnaik¹⁰, Lachelle D. Weeks¹¹, Gary Ho¹², Onima Chowdhury¹³, Adam Al-Hakim¹⁴, Scott Goldberg¹⁵, Marcela ferrada¹⁶, Sophie georgin-Lavialle¹⁷, Peter Grayson¹⁸, Emma Groarke¹⁹, Bhavisha Patel²⁰, Megan Sullivan²¹, Sarah A. Buckley²², Bryan G. harder²², Sandra Goble²², Matthew Koster¹⁰ and David Beck²³, ¹Vanderbilt University Medical Center, Nashville, TN, ²Institute of Rheumatology, Praha ², Czech Republic, ³The University of Texas MD Anderson Cancer Center, Houston, TX, ⁴University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom, ⁵Yokohama City University Graduate School of Medicine, Yokohama, Japan, ⁶Department of Biomedicine and Prevention, University of Rome Tor Vergata and Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, Clevland, OH, Rome, Italy, ⁷Lyon-Sud Hospital, Hospices Civils de Lyon, Paris and Université Claude Bernard, Lyon, France, ⁸Centre Hospitalier Universitaire Toulouse Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France, ⁹Department of Internal Medicine, Inflammation-Immunopathology-Biotherapy Department (DMU i³), Saint-Antoine University Hospital, ⁷⁵⁰¹² Paris, France, Paris, France, ¹⁰Mayo Clinic, Rochester, MN, ¹¹Dana Farber Cancer Institute, Boston, MA, ¹²New York University Grossman School of Medicine, VA New York Harbor Health Care System, Brooklyn, NY, ¹³Oxford University Hospitals’ NHS Foundation Trust and Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom, ¹⁴University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine,, Leeds, United Kingdom, ¹⁵New York University Grossman School of Medicine, Brooklyn, NY, ¹⁶University of Maryland, Bethesda, MD, ¹⁷Sorbonne university, Tenon hospital, DMU³ID, CEREMAIA, ERN RITA, Paris, France, ¹⁸National Institutes of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Chevy Chase, MD, ¹⁹National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, ²⁰National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Beltsville, MD, ²¹Mayo Clinic Arizona, Scottsdale, AZ, ²²Sobi Inc., Waltham, MA, ²³Center for Human Genetics and Genomics, NYU Grossman School of Medicine. Division of Rheumatology, Department of Medicine, NYU Grossman School of Medicine. Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA, New York, NY

Meeting: ACR Convergence 2025

Keywords: clinical trial, Disease Activity, Measurement Instrument, Miscellaneous Rheumatic and Inflammatory Diseases, Response Criteria

Session Information

Date: Sunday, October 26, 2025

Title: Abstracts: Miscellaneous Rheumatic & Inflammatory Diseases I: Focus on Auto-Inflammatory Diseases (0777–0782)

Session Type: Abstract Session

Session Time: 1:00PM-1:15PM

Background/Purpose: VEXAS syndrome is a recently described severe disease characterized by a complex overlap of inflammatory and hematologic features. Due to the severity and refractory nature of inflammation in VEXAS patients, establishing effective treatment strategies is challenging, particularly in the absence of validated tools to assess disease activity. Standardized disease activity indices (DAIs) are crucial for patient care and advancing clinical research in inflammatory disorders. To date, the only proposed – though not validated – DAI for VEXAS is the VEXASCAF, which evaluates disease activity based on the presence or absence of 11 equally weighted manifestations (Kirino Y, et al. Rheumatology (Oxford). 2024 Sep 28). While the VEXASCAF represents an important first step, it has limitations: it may not capture less commonly involved organ systems or be sufficiently sensitive to changes in disease severity. A more comprehensive and sensitive DAI could aid in clinical research and improve patient care.

Methods: Manifestations of VEXAS syndrome were previously identified by systematic literature review and expert feedback. The VEXAS-DAI was developed based on an expert advisory committee using modified Delphi methodology until consensus was reached (defined as ≥75% concurrence). All items were graded based on adapted Common Terminology Criteria for Adverse Events (CTCAE) criteria. Scoring was developed based on Physician Global Assessment of inflammation on 158 test cases. The final instrument was developed based on input from 24 VEXAS expert physicians worldwide.

Results: Consensus on the novel VEXAS-DAI was achieved after 4 rounds of interactive revisions. Scoring is based on severity of symptoms at the time of examination. The VEXAS-DAI includes 12 scored domains, each with a specified number of items (Table 1): inflammatory-type rash (2), chondritis (3), ophthalmologic involvement (5), periorbital involvement (1), joint (1), pulmonary (3), cardiovascular (3), genitourinary (1), neurologic (5), oral and gastrointestinal (3), renal (1), and constitutional symptoms (present or absent). Additionally, a thrombosis and thromboembolism domain is included but remains unscored. Scores range from 0 to 40.

Conclusion: The VEXAS-DAI is designed to measure active inflammation in patients with VEXAS syndrome. Work is ongoing to validate this instrument in the context of a clinical trial.This abstract has been accepted for publication by the European Alliance of Associations for Rheumatology (EULAR). The definitive copyedited version is available online at: www.ard.eular.org.

Table 1. VEXAS-DAI domains

Disclosures: K. Byram: None; H. Mann: AbbVie, 6, Eli Lilly, 6, Novartis, 6, Sobi, 2, 6, UCB, 6; D. Hammond: None; S. Savic: BioCryst, 2, Celldex, 2, CSL Behring, 2, 5, KalVista, 2, 6, Novartis, 2, 5, 6, Pharming, 2, 6, Phavaris, 2, Sobi, 2, Takeda, 2, 6; Y. Kirino: Amgen, 6, Novartis, 2, 6, Sobi, 2; C. Gurnari: Alexion, 5, Genesis Therapeutics, 2; M. Heiblig: AbbVie, 2, Astellas, 2, Blueprint, 2, BMS/Celgebe, 2, Jazz Pharmaceuticals, 2, Servier, 2; T. Comont: AbbVie, 6, Amgen, 6, BMS, 2, 6, CSL Behring, 6, Griffols, 6, Novartis, 2, 5, 6; A. Mekinian: Roche, 5; M. Patnaik: AstraZeneca, 1, epigenetix, 5, Kura Oncology, 5, Polaris, 5, Sobi, 1, Solu therapeutics, 5, stem line pharmaceuticals, 5; L. Weeks: AbbVie, 2, Sobi, 2, Vertex, 2; G. Ho: Aclaris Therapeutics, 2, Scilex Holding, 2; O. Chowdhury: Jazz Pharmaceuticals, 6, Novartis, 6; A. Al-Hakim: None; S. Goldberg: None; M. ferrada: UpToDate, 9; S. georgin-Lavialle: Novartis, 2, Sobi, 2; P. Grayson: None; E. Groarke: None; B. Patel: None; M. Sullivan: None; S. Buckley: Sobi, Inc., 3; B. harder: Sobi, Inc., 3; S. Goble: Sobi, Inc., 3; M. Koster: Amgen, 2; D. Beck: Alexion, 2, Genesis Therapeutics, 2, GSK, 2, Novartis, 2, Sobi, 2.

To cite this abstract in AMA style:

Byram K, Mann H, Hammond D, Savic S, Kirino Y, Gurnari C, Heiblig M, Comont T, Mekinian A, Patnaik M, Weeks L, Ho G, Chowdhury O, Al-Hakim A, Goldberg S, ferrada M, georgin-Lavialle S, Grayson P, Groarke E, Patel B, Sullivan M, Buckley S, harder B, Goble S, Koster M, Beck D. Development of a Disease Activity Index for the Assessment of VEXAS Syndrome (VEXAS-DAI) [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/development-of-a-disease-activity-index-for-the-assessment-of-vexas-syndrome-vexas-dai/. Accessed .

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