Predicted and actual 2-year structural and pain progression in the IMI-APPROACH knee osteoarthritis cohort

Eefje M van Helvoort, Mylène P Jansen, Anne C A Marijnissen, Margreet Kloppenburg, Francisco J Blanco, Ida K Haugen, Francis Berenbaum, Anne-Christine C Bay-Jensen, Christoph Ladel, Agnes Lalande, Jonathan Larkin, John Loughlin, Ali Mobasheri, Harrie H Weinans, Pawel Widera, Jaume Bacardit, Paco M J Welsing, Floris P J G Lafeber

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OBJECTIVES: The IMI-APPROACH knee osteoarthritis study used machine learning (ML) to predict structural and/or pain progression, expressed by a structural (S) and pain (P) predicted-progression score, to select patients from existing cohorts. This study evaluates the actual 2-year progression within the IMI-APPROACH, in relation to the predicted-progression scores. METHODS: Actual structural progression was measured using minimum joint space width (minJSW). Actual pain (progression) was evaluated using the Knee injury and Osteoarthritis Outcomes Score (KOOS) pain questionnaire. Progression was presented as actual change (Δ) after 2 years, and as progression over 2 years based on a per patient fitted regression line using 0, 0.5, 1 and 2-year values. Differences in predicted-progression scores between actual progressors and non-progressors were evaluated. Receiver operating characteristic (ROC) curves were constructed and corresponding area under the curve (AUC) reported. Using Youden's index, optimal cut-offs were chosen to enable evaluation of both predicted-progression scores to identify actual progressors. RESULTS: Actual structural progressors were initially assigned higher S predicted-progression scores compared with structural non-progressors. Likewise, actual pain progressors were assigned higher P predicted-progression scores compared with pain non-progressors. The AUC-ROC for the S predicted-progression score to identify actual structural progressors was poor (0.612 and 0.599 for Δ and regression minJSW, respectively). The AUC-ROC for the P predicted-progression score to identify actual pain progressors were good (0.817 and 0.830 for Δ and regression KOOS pain, respectively). CONCLUSION: The S and P predicted-progression scores as provided by the ML models developed and used for the selection of IMI-APPROACH patients were to some degree able to distinguish between actual progressors and non-progressors. TRIAL REGISTRATION:,, NCT03883568.

Original languageEnglish
Pages (from-to)147-157
Number of pages11
JournalRheumatology (Oxford, England)
Issue number1
Early online date16 May 2022
Publication statusPublished - 1 Jan 2023


  • Knee osteoarthritis
  • biomarkers
  • clinical trials and methods
  • study design


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