Evaluating Changes in Synovial Fluid Before and After GAE for Knee Osteoarthritis

To estimate the correlation between objective changes in synovial fluid biomarkers (IL-6, VEGF and MCP-1) and changes in subjective symptomatic response (KOOS) 3 months after treatment of knee osteoarthritis with GAE.

KOOS is a validated knee osteoarthritis scoring system that involves five subscales: pain (9 questions), symptoms (7 questions), activities of daily living (17 questions), sport/recreation (5 questions), knee-related quality of life (4 questions).

Trials demonstrate maximum symptomatic response to GAE at 3 months, and sustained improvement for at least 1-2 years. Improvement in KOOS reflects symptomatic response to treatment. This will determine whether changes in the local inflammatory environment in the knee synovium correlate with symptomatic response to GAE. This would also help elucidate whether the mechanism of action of GAE is likely attributable to inflammation.

The WORMS scoring system is a semi-quantitative assessment of 14 features found on knee MRI. The WORMS synovitis subscale is scored based on the distension of the joint capsule and is graded from 0 to 3 in terms of the estimated maximal distention of the synovial cavity with 0=normal, grade 1=<33% of maximum potential distention grade 2=33%-66% of maximum potential distention and grade 3=>66% of maximum potential distention

WORMS will be used to determine changes in synovial fluid biomarkers pre-treatment and 3 months after treatment of knee osteoarthritis with GAE.

The MRI will also be evaluated using the Multicenter Osteoarthritis Study grading system for synovitis.

The Multicenter Osteoarthritis Study (MOST) grading system for knee synovitis is an alternative to the WORMS synovitis score and incorporates a larger range of grading. The higher the score, the worse the synovial inflammation. The scoring ranges from 0-13, with 0-4 for normal or equivocal synovitis, 5-8 for mild synovitis, 9-12 for moderate synovitis, and 13 or greater for severe synovitis.

Patients will be given VAS questionnaires to give subjective responses to changes in pain levels and its effect on activities of daily living.

VAS is calculated by scoring pain level between 0-100. This is asked verbally "How would you rate your pain in the affected knee?"

These questionnaires will be given at time points: screening, 1 month after GAE, 3 months, 6 months and 12 months.

The Knee Injury and Osteoarthritis Outcome Score involves five subscales: pain (9 questions), symptoms (7 questions), activities of daily living (17 questions), sport/recreation (5 questions), knee-related quality of life (4 questions).

Patients will be given KOOS questionnaires to give subjective responses to changes in pain levels and its effect on activities of daily living.

These questionnaires will be given at time points: screening, 1 month after GAE, 3 months, 6 months and 12 months.

To estimate the correlation between objective measures of knee pain or inflammation (performance-based measures, contrast-enhanced MRI synovitis scores) to symptomatic response (KOOS) 3 months after treatment of knee osteoarthritis with GAE. This may provide additional assurance in the form of objective measures of response in a disease that is known to have a strong placebo effect.

To estimate the correlation between changes in a larger set of synovial fluid biomarkers (54markers across inflammation, chemotaxis, angiogenesis, and immune system regulation pathways) and changes in subjective scores (KOOS) 3 months after treatment. This will further develop the interrogation of which microenvironment pathways in the knee synovium correlate with symptomatic response to GAE.