Serum Calprotectin as predictor of Rheumatoid Arthritis disease severity and Mortality

Objective: To evaluate the clinical utility of serum calprotectin (sCAL) as a biomarker of disease activity, disease severity, cardiovascular risk, and mortality in inflammatory rheumatic diseases (IRDs). Methods: Serum calprotectin was measured in 2677 patients with IRDs, including 1472 rheumatoid arthritis (RA), 771 axial spondyloarthritis (axSpA), and 434 psoriatic arthritis (PsA) patients enrolled in the Swiss Clinical Quality Management in Rheumatic Diseases registry, as well as 248 healthy blood donors. Associations with disease activity, radiographic progression, cardiovascular biomarkers, incident major adverse cardiovascular events (MACE), and mortality were evaluated using receiver operating characteristic, Cox regression, and Kaplan-Meier models. Results: sCAL concentrations were significantly higher in RA than in axSpA, PsA, or healthy blood donors. Although diagnostic discrimination between IRDs was modest (Area under the curve (AUC): 0.56), elevated sCAL identified a subset of patients with RA characterized by higher disease activity, higher autoantibody levels, and accelerated radiographic progression, performing better than CRP for the assessment of inflammatory activity, particularly for the discrimination of active synovitis (SJC28≥4, AUC 0.67 vs 0.62, p=0.012), even in patients with normal CRP concentrations. Elevated sCAL was independently associated with increased all-cause mortality (HR:2.99; 95% confidence interval (95%CI):1.87-4.78), cardiovascular mortality (HR:7.49;95%CI:1.50-37.55), respiratory mortality (HR: 5.89; 95%CI:1.97-17.62), and incident MACE (HR: 2.10; 95%CI: 1.04-4.24). Furthermore, sCAL correlated with high-sensitivity cardiac troponin T and NT-proBNP concentrations, independently of lipid profile. Conclusions: Serum calprotectin is a clinically relevant biomarker in RA that reflects both disease activity and severity, independently identifying patients at increased cardiovascular risk and mortality, supporting its potential role in disease monitoring and risk stratification.