Exploring glucocorticoid dose-response patterns in VEXAS syndrome: a pilot retrospective study

VEXAS syndrome is characterized by high glucocorticoid (GC) requirements and frequent relapses during tapering, yet dose-response relationships remain poorly defined. We conducted a pilot study to assess the feasibility of granular longitudinal treatment-line reconstruction and to explore GC dose-response patterns associated with disease activity and flare risk. In this retrospective single-center study, we reconstructed detailed treatment trajectories of patients with VEXAS syndrome. Disease courses were segmented into treatment-line periods defined by any therapeutic modification, including GC dose changes. For each period, GC dose, concomitant therapies, and clinical activity were recorded. Associations between GC dose and disease activity were analyzed using multivariable models adjusting for concomitant treatments. Twelve patients were included, representing 315 treatment-line periods over a mean follow-up of 45 months. Mean annual GC exposure was 3.27 ± 2.26 g per patient. Higher GC dose (continuous variable) was independently associated with lower odds of clinical activity (aOR 0.91 per mg increase [95% CI 0.88-0.94], p < 0.001). Exploratory threshold analyses suggested increased flare risk below approximately 15 mg/day (or 0.2 mg/kg/day), with a lower-risk plateau above 20 mg/day. The increased flare risk below 15 mg/day remained significant after adjustment for concomitant therapies (HR 0.24 [95% CI 0.11-0.54], p = 0.001). Organ-specific analyses suggested heterogeneous glucocorticoid sensitivity, with higher doses appearing required for lung involvement and lower doses appearing sufficient for fever, skin, and joint manifestations. This pilot study demonstrates the feasibility of detailed treatment-line reconstruction in VEXAS syndrome and identifies GC dose-response trends. These preliminary findings provide planning parameters for a future adequately powered study aimed at validating dose thresholds and refining tapering strategies in VEXAS.