Pathological tissue formation and degradation biomarkers correlate with patient reported pain outcomes: an explorative study

Abstract

Background: The lack of disease modifying drugs in Osteoarthritis (OA) may be attributed to the difficulty in robust response based on patient-reported outcomes (PROs) linked to drug mechanism of action. Joint tissue turnover biomarkers are associated with disease progression. A subset of patients has elevated serum levels of CRP metabolite (CRPM). This explorative study investigates the associations between PROs and joint tissue turnover markers in patients with high or low CRPM. Methods: Serum of 146 knee OA patients of the New York Inflammation cohort and 21 healthy donors were assessed for biomarkers of collagen degradation (C1M, C2M, C3M, C4M), formation (PRO-C1, PRO-C2, PRO-C3, PRO-C4), and CRPM. Mean (SD) age was 62.5 (10.1); BMI, 26.6 (3.6); 62% women; and, 67.6% had symptomatic OA. WOMAC pain, stiffness, function, and total were recorded at baseline and at two-year follow-up. Associations were adjusted for race, sex, age, BMI, and NSAID. Results: There was no difference in markers between donors and patients. C2M correlated with the WOMAC scores in all CRPM groups. Significant correlations were observed between PROs and PRO-C4, C1M, and C3M in the CRPMhigh group. The best predictive models for improvement were found for function and total with AUCs of 0.74 (p ​< ​0.01) and 0.78 (p ​< ​0.01). The best predictive models for worsening were found for function and total with AUCs of 0.84 (p ​< ​0.01) and 0.80 (p ​< ​0.05). Conclusion: We hypothesize that collagen markers are prognostic tools for segregating patient populations in clinical trials.

Keywords

• Protein
• Epitope
• Assay