Development of a Disease Activity Index for the Assessment of VEXAS Syndrome (VEXAS-DAI)
Abstract format and assignment number: Oral presentation 0777
Date: Sunday, 26th October 2025
Presenting author: M. Koster (USA)
Given the clinical heterogeneity of VEXAS syndrome, standardized disease activity tools have been lacking. Through an international Delphi consensus, the VEXAS Disease Activity Index (VEXAS-DAI) was developed. It is a 12-domain composite score covering key inflammatory and organ-specific features. Severity grading was adapted from CTCAE and calibrated against physician global assessments in 163 cases. The VEXAS-DAI is the first consensus-based tool to quantify VEXAS disease activity and will be prospectively validated in future studies.
Interim Results of a Randomized Placebo-Controlled Study of the IL-1 Inhibitor Goflikicept in Patients with Familial Mediterranean Fever
Abstract format and assignment number: Oral presentation 0779
Date: Sunday, 26th October 2025
Presenting author: S. Ugurlu (Turkey)
A phase 2 trial evaluated goflikicept, a novel IL-1 inhibitor, in adults with colchicine-refractory Familial Mediterranean Fever (FMF). A complete response (attack resolution, no new attacks) was achieved in 64% of goflikicept patients versus 7% of placebo patients (p=0.004). Most patients also achieved low disease activity with marked CRP reduction. Adverse events were mild-to-moderate with no new safety signals, showing promising efficacy and a favorable safety profile comparable to existing IL-1 inhibitors.
Comprehensive Mass Cytometry Analyses of Disease-Related Cells in Adult-Onset Still’s Disease
Abstract format and assignment number: Oral presentation 0781
Date: Sunday, 26th October 2025
Presenting author: H. Yoshida (Japan)
Mass cytometry was used to profile immune cells in 50 adult-onset Still’s disease (AOSD) patients and 21 healthy controls. Active AOSD was characterized by reduced B cells, NK cells, and γδ T cells. Conversely, 56 immune cell clusters were expanded, notably intermediate monocytes and effector memory CD4+CD8+ T cells. These expanded subsets normalized in remission, suggesting a key role in AOSD pathogenesis and their potential as new therapeutic targets.
Tibial Bone Microstructure and Histomorphometry in Individuals With CPPD
Abstract format and assignment number: Poster 1142
Date: Monday, 27th October 2025
Presenting author: S. Tedeschi (USA)
This pilot study compared tibial bone microstructure in five CPPD patients undergoing total knee replacement against matched controls. Using micro-CT and histology, researchers found CPPD samples had lower bone volume/tissue volume (BV/TV) and higher osteoclast surface and number. This suggests increased bone resorption and structural weakness in CPPD-affected compartments. The findings support previous epidemiological data linking CPPD to osteopenia and a higher risk of fracture.
Inflammatory Cell Death and Impaired Efferocytosis Drive Monocyte and Macrophage Dysfunction in VEXAS Syndrome
Abstract format and assignment number: Oral presentation 2582
Date: Tuesday, 28th October 2025
Presenting author: P. Breillat (France)
This study showed that mutations in UBA1 drive inflammation and cytopenias in VEXAS syndrome. In vitro monocytic models with mutant UBA1 showed enhanced ZBPK1-dependent inflammatory cell death and dysregulated NF-kB signaling. Derived macrophages secreted high levels of proinflammatory cytokines and had impaired efferocytosis (defective apoptotic cell clearance) linked to reduced MERTK expression. These findings, confirmed in patient samples, suggest inflammatory cell death and poor cell clearance are central to VEXAS pathogenesis.
Nanoencapsulated Sirolimus Plus Pegadricase Reduced Disease Burden in Patients With Uncontrolled Gout: Results From the Phase 3 DISSOLVE Trials
Abstract format and assignment number: Oral presentation 2587
Date: Tuesday, 28th October 2025
Presenting author: P. Khanna (USA)
A post hoc analysis of the Phase 3 DISSOLVE trials evaluated NASP (nanoencapsulated sirolimus plus pegadricase) in uncontrolled gout patients. NASP combines an immunomodulator with a pegylated uricase. After 6 doses, NASP-treated patients showed significant serum urate (sUA) reductions (mean changes -88% to -94%) versus placebo (-0.3%), with mean sUA remaining ≤ 2.0 mg/dL. NASP also led to greater reductions in tender and swollen joints (up to -92% and -91% respectively). Patient-reported quality of life (SF-36, HAQ-DI pain) improved significantly.
Nanoencapsulated Sirolimus Plus Pegadricase (NASP) Demonstrates a Reduction in Gout Flares: Results From the Phase 3 DISSOLVE Studies
Abstract format and assignment number: Oral presentation 2588
Date: Tuesday, 28th October 2025
Presenting author: A. Gaffo (USA)
A pooled analysis of the Phase 3 DISSOLVE trials found that NASP (Nanoencapsulated Sirolimus plus Pegadricase) significantly reduced gout flares in patients with uncontrolled gout. NASP combines an immunomodulator with a pegylated uricase. After six treatment cycles, gout flare rates dropped to ~3% in NASP groups, compared to 22% for placebo at weeks 21-24. Flare frequency was 4-5 times lower with NASP, suggesting it effectively lowers urate levels and prevents flares through combined uricase activity and immunomodulation.
Elvis Hysa
Elvis is a Rheumatologist and PhD Candidate at the Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, University of Genova, Italy. His research focuses primarily on clinical and translational studies in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), imaging aspects of systemic sclerosis and other autoimmune connective tissue diseases (particularly capillaroscopy and skin ultrasound), and rheumatic-immune related adverse events in oncologic patients following immune checkpoint inhibitor therapy. He is a member of the EMEUNET Newsletter Sub-Committee and is actively involved in international task forces on imaging and treatment-related aspects in PMR and GCA.