Active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) requires intensive immunosuppressive therapy, but continued treatment after remission is achieved can cause serious harm. Reliable biomarkers to confirm remission are lacking, forcing clinicians to prolong cost-intensive and toxic therapy unnecessarily. Routine markers, such as C-reactive protein and anti-neutrophil cytoplasmic antibodies, lack sensitivity and specificity for the remission status, failing to guide treatment de-escalation safely. After adjusting for patient characteristics and clinical variables, we explored the plasma proteome to identify reliable biomarkers of disease remission in patients with AAV. We applied a two-tiered proteomics strategy combining global discovery with targeted validation to identify a protein signature of remission. The resulting 7-protein panel was successfully implemented in a targeted mass spectrometry-based assay, with diagnostic performance confirmed in an independent patient cohort. The panel consistently outperformed routine markers. Our findings suggest that this panel may serve as a starting point for developing a clinical tool to support decision-making, with the potential to reduce treatment-related burden, mitigate toxicity, and lower healthcare costs. Moreover, our confounder-controlled proteomics approach provides a scalable blueprint for biomarker discovery in complex inflammatory diseases.