Multivariable modeling of biomarker data from the phase 1 Foundation for the NIH Osteoarthritis Biomarkers Consortium
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OBJECTIVE: To determine the optimal combination of imaging and biochemical biomarkers to predict knee osteoarthritis (OA) progression.
METHODS: Nested case-control study from the FNIH OA Biomarkers Consortium of participants with Kellgren-Lawrence grade 1-3 and complete biomarker data (n=539 to 550). Cases were knees with radiographic and pain progression between 24-48 months from baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) with p<0.10 in univariate analysis were selected, including MRI (quantitative (Q) cartilage thickness and volume; semi-quantitative (SQ) MRI markers; bone shape and area; Q meniscal volume), radiographic (trabecular bone texture (TBT)), and serum and/or urine biochemical markers. Multivariable logistic regression models were built using three different step-wise selection methods (complex vs. parsimonious models).
RESULTS: Among baseline biomarkers, the number of locations affected by osteophytes (SQ), Q central medial femoral and central lateral femoral cartilage thickness, patellar bone shape, and SQ Hoffa-synovitis predicted progression in most models (C-statistics 0.641-0.671). 24-month changes in SQ MRI markers (effusion-synovitis, meniscal morphology, and cartilage damage), Q central medial femoral cartilage thickness, Q medial tibial cartilage volume, Q lateral patellofemoral bone area, horizontal TBT (intercept term), and urine NTX-I predicted progression in most models (C-statistics 0.680-0.724). A different combination of imaging and biochemical biomarkers (baseline and 24-month change) predicted radiographic progression only, with higher C-statistics (0.716-0.832).
CONCLUSION: This study highlights the combination of biomarkers with potential prognostic utility in OA disease-modifying trials. Properly qualified, these biomarkers could be used to enrich future trials with participants likely to progress.
Originalsprog | Engelsk |
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Tidsskrift | Arthritis Care & Research |
Vol/bind | 74 |
Udgave nummer | 7 |
Sider (fra-til) | 1142-1153 |
ISSN | 2151-464X |
DOI | |
Status | Udgivet - 2022 |
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