Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry.

Objective: We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study.

Methods: Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure VEXASCAF assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels and treatments were also recorded at enrolment and 3 months after enrolment. All exons of ubiquitin-like modifier activating enzyme 1 (UBA1) were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients.

Results: Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including three deaths, four malignancies from two cases, two thromboses and 13 infections (including four mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling and pain) were the most common AEs.

Conclusions: Patients with VEXAS syndrome required high-dose glucocorticoids to reduce disease activity, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.