Lupus & antiphospholipid syndrome
Metabolomic profiling of patients with lupus nephritis reveals unique metabolites that are modulated through type I interferon inhibition by anifrolumab treatment in a phase 2 trial
Authors' conclusion
Our findings establish a connection between type I interferon signalling, pyrimidine metabolism and uremic toxins in patients with LN and support the evaluation of urine uracil as a potential biomarker of response to anifrolumab.
Study context
- Population
- Patients with lupus nephritis (LN) in the phase 2 TULIP-LN trial; serum and urine samplesserum 128, urine 119 patients
- Comparison
- Standard therapy plus intravenous anifrolumab vs standard therapy plus placebo
Methodological detailsuntargeted metabolomics, in vitro validation model
- Untargeted metabolomics
- In vitro validation model
Primary result
As reported in the abstract
Metabolites modulated by anifrolumab
- Serum: indoxyl sulfate (IS) and cytosine most modulated by anifrolumab; baseline levels correlated with measures of kidney damage
- Urine: uracil and cytosine most modulated by anifrolumab; levels associated with serological markers of disease activity
- In vitro: anifrolumab reduced markers of vascular dysfunction and inflammation upregulated by IS
- Baseline urine uracil levels predicted response to anifrolumab intensive regimen at Week 52
Original publication
Metabolomic profiling of patients with lupus nephritis reveals unique metabolites that are modulated through type I interferon inhibition by anifrolumab treatment in a phase 2 trial. RMD Open. Published 5 October 2025. doi:10.
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