0260: Development of a Consensus Definition of VEXAS Flare for Use in Clinical Research

Background/Purpose: VEXAS syndrome is a recently identified, severe systemic hemato-inflammatory disease with a complex and heterogeneous clinical presentation. The disease is associated with significant morbidity and mortality, with most patients experiencing recurrent flares or persistent symptoms despite anti-inflammatory therapy. Accurate and standardized measures of disease activity are critical for understanding disease progression, optimizing management, and conducting effective clinical trials. Before developing a disease activity instrument, it is essential to define disease activity, such as VEXAS flare. The absence of universally accepted definitions of VEXAS flare has significantly hindered these efforts. Developing consensus criteria for a VEXAS flare will promote consistency in research, the evaluation of therapeutic interventions, and most importantly will improve patient care.

Methods: A 9-member international expert advisory committee, including both hematologists and rheumatologists, developed a consensus definition of VEXAS flare using modified Delphi methodology. Clinical manifestations of VEXAS syndrome were identified by a systematic literature review. Committee members developed a conceptual framework for flare definition, proposed revisions, and voted on changes until consensus was reached (defined as ≥75% concurrence). To facilitate revisions, a moderator amended VEXAS flare definition text, synthesizing similar proposed changes, and providing multiple drafts for consideration for dissimilar proposals.

Results: A total of 4 revision rounds were conducted from May to July of 2024, and consensus was reached on the definition of VEXAS flare as an active inflammatory manifestation of VEXAS syndrome requiring escalation in glucocorticoid therapy. Three categories of flare were established: A) recurrence of a prior documented VEXAS manifestation; B) development of a new VEXAS-defining inflammatory sign; or C) development of an inflammatory sign not meeting criteria for categories A or B. The panel agreed upon the need for an independent adjudication committee to aid in the determination of flares, particularly in the context of category C manifestations, during clinical trials.

Conclusion: A consensus definition of VEXAS flare provides uniform criteria for defining and characterizing recurrence of VEXAS disease activity. Future efforts will focus on refining this definition through its application and performance in clinical trials.

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