#3-71E. Dual-Targeting SLE with Vorinostat (ArthritisRheumatol, 2026)

Can we develop a therapeutic option that simultaneously targets the root pathogenic mechanisms of refractory systemic lupus erythematosus (SLE)? This episode discusses a study identifying vorinostat, a clinically approved histone deacetylase (HDAC) inhibitor, as a dual suppressor of type I interferon (IFN-I) overproduction and aberrant B cell differentiation13. The researchers demonstrated that vorinostat targets HDAC6, thereby inhibiting TBK1 phosphorylation and IRF3 nuclear translocation to reduce IFN-I, while simultaneously suppressing essential transcription factors required for plasma cell differentiation. In SLE-prone mouse models, this intervention effectively decreased IFN-I induction and B cell maturation, ultimately improving survival rates and alleviating lupus nephritis. The most novel clinical takeaway is that an existing anticancer drug could be repurposed to simultaneously block the two major pathogenic pathways of SLE via HDAC6 inhibition. However, when critically appraising this study, clinicians must note that the findings are primarily based on in vitro and mouse models, meaning that clinical efficacy and long-term safety profiles in human patients remain unestablished. For physicians treating autoimmune conditions, this research is crucial as it highlights a promising drug repositioning strategy, potentially paving the way for expanded treatment options for patients with refractory SLE.

Citation: Takehiro Hirayama, Hyota Takamatsu, et al. Identification of Histone Deacetylase Inhibitor Targeting Type I Interferon and B Cell Abnormalities in Systemic Lupus Erythematosus. Arthritis & Rheumatology. 2026. DOI: 10.1002/art.43434

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.