VEXAS syndrome: a Swiss national retrospective cohort study

Abstract

AIMS OF THE STUDY: VEXAS syndrome is a recently discovered monogenic auto-inflammatory disease due to a somatic mutation in UBA1 gene that manifests with rheumatologic and hematologic features. In this report, we present the first Swiss cohort, detailing its manifestations and treatment outcomes among Swiss patients.

METHODS: Nine Swiss hospitals were contacted. Data was retrospectively filled by each treating physician in a case report form (CRF). All CRFs were collected and analyzed by the principal investigator and its co-investigators.

RESULTS: We identified 23 patients and described 17 of them between July 2022 and 2023. All were males. They presented with skin manifestations (88%), general symptoms (82%), venous thromboembolism (59%), ocular manifestation (59%), lung infiltrates (59%) and articular manifestations (47%). Central nervous system and kidney manifestations were very rare whereas heart and digestive manifestations were absent. Macrocytic anemia was present in all patients throughout the disease progression but only in 2/3 of patients (12/17, 71%) at the time of diagnosis. Clinical response was reached in all cases treated with ruxolitinib (4/4, 100%), upadacitinib (1/1, 100%), azacytidine (AZA, 5/5, 100%) and hematopoietic stem cell transplantation (HSCT 2/2, 100%). All deaths were attributed to infections (5/5, 100%).

CONCLUSION: This study corroborates the clinical spectrum of VEXAS syndrome as described in other cohorts. It suggests that VEXAS syndrome isn't limited to macrocytic anemia patients. Azacytidine seems to be the appropriate first-line treatment in case of myelodysplastic syndrome (MDS). Conversely, JAK inhibitors, especially ruxolitinib, seem to be the best option in absence of MDS. For refractory cases, HSCT seems to be the only curative treatment.