FRI0387 A PROGNOSTIC MODEL OF PRE-RADIOGRAPHIC KNEE OSTEOARTHRITIS: DATA FROM THE OSTEOARTHRITIS INITIATIVE

Abstract

Background:The improvement of the existing diagnostic methods to detect pre-radiographic knee OA (KOA) may facilitate the development of preventive strategies. It has been postulated that combining biochemical with clinical markers, may increase the prognostic power to detect who is at high risk for developing KOA.Objectives:To validate and qualify the ability of 6 proteins with biomarker potential to generate a prognostic model of knee OA prediction through the combination of validated OA biomarkers and clinical markers.Methods:In thevalidation phase(Figure 1), 749 sera at the baseline visit belonging to participants from the Osteoarthritis Initiative (OAI) Cohort were randomly selected to blindly quantify 6 biomarkers using in-house custom sandwich microarrays built using the xMAP technology. Among these, only 540 participants have a Kellgren and Lawrence (KL) grade = 0-1 at the beginning of the OAI study in at least one knee. After a follow-up period of 96 months, 209 participants developed KOA in at least one knee (KL ≥ 2) and were classified as incident group, whereas 331 did not developed the disease (KL = 0-1) and were classified as not-incident group. Statistical differences between the outcome groups were assessed by non-parametric Mann-Whitney U tests. In thequalification phase(n=540), univariate regression analyses were carried out to investigate whether the individual biomarkers were associated with the risk of KOA development. A clinical prognostic model was defined by stepwise regression analysis using clinical non-radiographic variables significantly associated with the OA incidence. The utility of the potential biomarkers, alone or in combination, was evaluated by comparing the Area Under the Curve (AUC) of the clinical prognostic model with the biomarkers plus clinical prognostic models. In addition, senFigure 1.Study desingResults:The incident group showed significant higher serum concentrations at the baseline visit (p < 0.05) for all the potential biomarkers analyzed in this study. Moreover, 5 of them were also significantly associated with the future appearance of radiographic KOA, yielding Odds Ratios (OR) ≥ 10 per 10 µg/ml increase. Among all the possible combinations, the inclusion of 2 biomarkers to the clinical prognostic model showed a significant improvement of the predictive capacity (AUCs = 0.78 vs 0.82, p= 0,044) with 65% (95% Confidence Interval (95%CI): 60-70%) specificity and 88% (95%CI: 81-91%) sensitivity. Variables included in the regression model and all metrics comparing the biomarkers plus clinical prognostic model with the clinical prognostic model are shown in Figure 2A. The ROC curves of the biomarkers-only model, clinical prognostic model and biomarkers plus clinical prognostic model are represented in Figure 2B.Figure 2.(A) Multivariate regression analysis (B) ROC curves of the modelsConclusion:We have generated a prognostic model for the prediction of KOA by combining biomarkers and clinical variables, which showed a putative utility in the clinical setting by improving the predictive capacity of a clinical prognostic model to identify patients at a higher risk to develop radiographic KOA.Disclosure of Interests:Maria Camacho Encina: None declared, Vanesa Balboa-Barreiro: None declared, Ignacio Rego-Perez: None declared, Rocío Paz González: None declared, Valentina Calamia: None declared, Lucía Lourido: None declared, Cristina Ruiz-Romero: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research & Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer