Elevated Serum Proadrenomedullin Levels in Rheumatoid Arthritis Versus Spondyloarthritis: Insights From a Biobank Cohort

Objective: Proadrenomedullin (pro-ADM) is a peptide implicated in immunomodulation, with higher levels observed in inflammatory conditions, cardiovascular impairment, and sepsis. Although extensively studied in acute disorders, its potential as a biomarker in inflammatory arthritis remains underexplored. This study aims to examine serum pro-ADM levels across different types of inflammatory arthritis and to investigate correlations with disease characteristics. Methods: We included 163 patients with inflammatory arthritis who were prospectively enrolled in our institutional Biobank. Among them, 99 patients had rheumatoid arthritis (RA), 36 patients had psoriatic arthritis (PsA), 22 patients had axial spondyloarthritis (axSpA), and 6 patients had undifferentiated spondyloarthritis (uSpA). Serum pro-ADM levels were measured using enzyme-linked immunosorbent assay, with cross-sectional assessment at baseline in all patients and longitudinal follow-up in a subset of 31 patients with RA. Results: At baseline, patients with RA exhibited significantly higher serum pro-ADM levels (median 51.7 pg/mL) in comparison to PsA, axSpA, and uSpA (median values between 33.9 and 35.6 pg/mL; all P < 0.001). Pro-ADM showed good discriminative ability in distinguishing RA from SpA but had no correlation with markers of inflammation, disease duration, or disease activity indices. In patients with RA with follow-up data, pro-ADM levels exhibited a significant decrease from 52.5 to 30.1 pg/mL after six months (P = 0.023). However, changes in pro-ADM did not correlate with changes in the Disease Activity Score in 28 joints using the C-reactive protein level. Conclusion: Serum pro-ADM levels are markedly elevated in RA relative to SpA, although they do not correlate with inflammatory burden or disease activity. In RA, pro-ADM levels decrease following treatment initiation or modification; nonetheless, they lack predictive value for treatment response. These findings suggest that pro-ADM reflects disease-specific pathophysiologic differences rather than representing a dynamic biomarker.