JAK Inhibitors for Treatment of VEXAS Syndrome: A Systematic Review of 186 Cases

Abstract

Objectives: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an autoinflammatory disease with a wide spectrum of manifestations and no standard treatment. Janus kinase inhibitors (JAK-I) are small-molecule drugs that affect many molecular pathways. We aim to investigate the safety and efficacy of JAK-I in the treatment of VEXAS syndrome.Methods: A systematic search was conducted using MeSH terms/keywords related to JAK-I and VEXAS syndrome through PubMed/Medline, Scopus, Web of Science, and Embase until July 6, 2025.Results: We included 29 articles: 8 cohort, 8 case series, and 13 case reports. Our study includes data for 186 cases. The mean age was 69.64 years, and 83.33 were male. The most frequent manifestations were skin lesions (64.51), fever (64.51), arthritis and arthralgia (61.29), lung involvement (31.72), and venous thrombosis (24.19). In general, 33.87 had a complete response, and 29.57 had a partial response. Ruxolitinib was used in 117 patients. Thirty-four out of 117 (29.06) experienced complete to partial remission. Tofacitinib was used in 31 patients. About 29 of them showed complete to partial remission. Baricitinib was used in 25 patients; 12 had complete remission, and 16 had partial remission. Upadacitinib was used in 13 patients, which led to a complete remission in 38.46. Filgotinib was used in four patients, leading to partial remission in one case. Among all, 36.55 showed adverse effects. Of these, eight were on Ruxolitinib, two on Tofacitinib, two on Baricitinib, and three on Upadacitinib.Conclusion: JAK-I seems to be a promising treatment option with tolerable adverse effects for VEXAS syndrome.