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

Abstract

<b>Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> JAK-I seems to be a promising treatment option with tolerable adverse effects for VEXAS syndrome.