Steroid-Sparing Effects of Afimetoran in SLE Models

This study presents a technical report on the steroid-sparing effects of afimetoran, an equipotent dual antagonist of toll-like receptors 7 and 8, in the context of systemic lupus erythematosus (SLE). The research includes both in vitro and in vivo assessments. In vitro experiments utilized whole blood samples from patients with active SLE to evaluate the effects of afimetoran on interferon signatures, cytokine production, and resistance to prednisolone-induced apoptosis in plasmacytoid dendritic cells and B cells. In vivo, the efficacy of afimetoran was tested in established mouse models of lupus nephritis, including MRL/lpr, NZB/W-F1, and BXSB strains. Results indicated that afimetoran significantly suppressed kidney injury markers and maintained efficacy after the withdrawal of prednisolone. The findings suggest that afimetoran may provide a viable alternative to glucocorticoids in managing SLE, potentially improving patient outcomes while minimizing steroid-related side effects.