Objectives Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE) and is partially driven by type I interferon (IFN) signaling. Anifrolumab, an approved treatment for patients with SLE, has been investigated in a phase 2 trial in patients with LN receiving standard therapy (TULIP‐LN, NCT02547922). We studied the impact of anifrolumab treatment on urinary biomarker expression in patients with LN through proteomic analysis of samples from TULIP‐LN. Methods Urine samples were collected at Weeks 0, 12, and 48, from patients treated with the anifrolumab basic regimen (BR; n=35), intensified regimen (IR; n=42), or placebo (n=35) in addition to standard therapy, and analyzed for the presence of 197 proteins. The impact of anifrolumab relative to placebo on prespecified biomarkers linked to histological activity was assessed, and a comparison of responders versus nonresponders was conducted on proteins detected in ≥75% of samples. Results Anifrolumab treatment significantly reduced urinary CD163 and MCP‐1 expression at Week 12 versus placebo, including in patients classified as proteinuric nonresponders across all regimens. By Week 48, biomarker levels declined in all groups, indicating that standard therapy alone can eventually suppress intrarenal inflammation, but with slower kinetics. Proteomic analyses further revealed that anifrolumab was superior to placebo in reducing the proteomic inflammatory signature, regardless of responder status. Conclusion Compared with placebo, anifrolumab treatment significantly reduced urinary biomarkers of renal histological activity in patients with LN, which may accelerate the resolution of intrarenal inflammation, potentially preventing damage accrual.
Fava et al. (Mon,) studied this question.
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