Potential surrogate outcomes in individuals at high risk for incident knee osteoarthritis

To study potential surrogate outcomes for osteoarthritis (OA) incidence by evaluating the association of short-term changes in clinical and imaging biomarkers with long-term clinical knee OA incidence.

Middle-aged women with overweight/obesity, but free of knee symptoms were recruited through their general practitioners. At baseline, after 2.5 years, and after 6.5 years, questionnaires, physical examination, radiographs, and Magnetic resonance imaging (MRI) scans were obtained. The percentage of knees with a minimal clinically important difference for knee pain severity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/stiffness/function, and joint space narrowing, and of those with progression/regression of medial knee alignment, chronic knee pain, radiographic osteophytes, and cartilage defects, bone marrow lesions, osteophytes, and effusion/synovitis on MRI were determined. For each of these potential surrogate outcomes with ≥10% improvement or progression in the population over 2.5 years, the association with incident clinical knee OA, defined using the combined ACR-criteria, after 6.5 years was determined.

Most pre-defined potential surrogate outcomes showed ≥10% change in the population over 2.5 years, but only worsening of TF cartilage defects, worsening of TF osteophytes on MRI, and an increase in pain severity were significantly associated with greater clinical knee OA incidence after 6.5 years. These potential surrogate outcomes had high specificity and negative predictive value (89-91%) and low sensitivity and positive predictive value (20-28%) CONCLUSIONS: Worsening of TF cartilage defects and TF osteophytes on MRI, and increased pain severity could be seen as surrogate outcomes for long-term OA incidence. However, higher positive predictive values seem warranted for the applicability of these factors in future preventive trials.