Towards Classification Criteria for Early-stage Knee Osteoarthritis: A Population-based Study to Enrich for Progressors

Objective: To facilitate a greater likelihood of favorable response to new disease-modifying therapies, recruitment of patients at an earlier stage of their disease into clinical trials may be an attractive strategy. Hence, there is a need to develop widely accepted classification criteria for early-stage knee osteoarthritis (OA). We have proposed a set of classification criteria for early-stage knee OA (2018 classification criteria) now being further refined. Here, we test the draft criteria for enrichment for clinical and structural progression.

Design: Performance of the 2018 classification criteria for early stage knee OA was tested using data from the Osteoarthritis Initiative (OAI). The OAI comprises data of 4796 men and women aged 45-79 years with or at risk for knee OA at baseline. Based on the 2018 classification criteria, a knee with Kellgren & Lawrence (K&L) grade of 0-I, two out of four Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales equal or less than 85, and presence of at least one of joint line tenderness or crepitus, was considered as early-stage knee OA. Knees with K&L grade 0-I that did not fulfill the 2018 criteria, were considered as controls. Logistic regression analysis was used to evaluate the predictive performance of the criteria set for structural as well as clinical progression. We further explored the discriminatory capability of criteria by including the average KOOS score, and relevant clinical examination findings such as the presence of effusion and/or Heberden's nodes.

Results: We identified 1315 (27%) knees from OAI fulfilling the 2018 early-stage knee OA classification criteria. The female to male ratio was higher in the early knee OA group compared to controls. The early-stage knee OA group were on average slightly younger and had higher body mass index vs controls (mean [SD] age: 59.2 [8.9] years vs. 60.2 [9.1] and mean [SD] BMI 28.3 [7.0] vs. 26.8 [6.0]). By applying the 2018 criteria, there was a substantial enrichment compared to controls at 48 and 96 months for both structural (OR=1.1-1.4, and AUC=0.72-0.74) and clinical progressors (OR=2.1-2.5, 95% and AUC=0.66). Expanding the clinical examination findings by including joint effusion and/or Heberden's nodes improved the enrichment for both structural and clinical progressors (OR=4.2, 95% confidence interval=3.2-5.5 and OR=3.3, 95% confidence interval=2.8-3.5, respectively). Replacing scoring of the 4 separate KOOS domains by a KOOS score performed comparably.

Conclusions: The proposed 2018 early-stage knee OA classification criteria showed encouraging performance characteristics with regard to an enrichment for structural and clinical progression using longitudinal OAI data. Our results indicate that the addition of clinical findings improves the performance of previous criteria to define early-stage disease and risk for progression.