Objective The Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium aims to identify, develop, and qualify biomarkers to support drug development in knee osteoarthritis (OA). The project's second phase, the PROGRESS OA study, aims to externally validate prognostic and response biomarkers identified in the earlier phase (phase 1). Here we present results assessing external validation of prognostic imaging biomarkers. Design PROGRESS OA included data from the control arms of several completed randomized controlled trials (RCTs) for symptomatic knee OA. Radiographic progression was defined as joint space width loss (JSWL) ≥0.7 mm. Symptomatic progression was defined as increase of nine or more points in Western Ontario and McMaster Universities Arthritis Index pain (0–100 scale). Imaging biomarkers included quantitative measures of cartilage thickness and semiquantitative (SQ) assessments. Associations between baseline biomarkers and outcomes over 12 to 36 months were examined using logistic regression. Results A total of 320 participants from four RCTs were included. Forty‐one participants (13%) had JSWL ≥0.7 mm and 64 (20%) had worsening symptoms. In univariable logistic regression, measures of quantitative and SQ cartilage, SQ Hoffa‐synovitis, effusion‐synovitis, and meniscal extrusion were consistently selected to predict JSWL ≥0.7 mm, similar to phase 1. SQ Hoffa‐synovitis and lateral meniscal damage were consistently selected to predict symptomatic progression. Cross‐validated areas under the curve were 0.69 (95% confidence interval CI: 0.53–0.85) for JSWL ≥0.7 mm and 0.77 (95% CI: 0.65–0.87) for symptomatic progression. Conclusion The selected prognostic imaging biomarkers are candidates for enriching OA trials for structural and/or symptomatic progressors. Ongoing work includes pursuit of formal biomarker qualification by regulatory agencies, and the use of these biomarkers to capture structural progression with high sensitivity to change.
Collins et al. (Mon,) studied this question.