Half of all people with early knee osteoarthritis will never get worse, but doctors currently have no way to tell who they are. This is a major problem for clinical trials. When researchers test new treatments, they include everyone with knee osteoarthritis—including the many people whose condition is stable. This dilutes the results, making potentially effective drugs look useless. The result is that no treatments exist to slow or stop knee osteoarthritis from progressing, even though millions of people in the UK live with the condition. This project aims to change that. The researchers will follow four groups of people with early knee osteoarthritis for two to five years, measuring changes in pain and X-ray scores. They will analyse proteins in knee fluid and blood samples—including 7,000 proteins already measured in one large international study—to find biological markers that predict whether an individual’s condition will worsen, improve, or stay the same. If successful, this work would allow clinical trials to recruit only people likely to progress, making it far easier to test new treatments. It could also give patients and their doctors a clearer picture of what to expect, enabling earlier, more personalised treatment decisions.
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Background: Knee osteoarthritis affects millions of people in the UK. Over half of people with knee osteoarthritis don’t get worse (don’t ‘progress’) but we can’t test for this. Early on in osteoarthritis, when there is knee pain but not much change on X-ray, is when we could best prevent things from getting worse. Currently, clinical trials in osteoarthritis fail to find new treatments because they bunch everyone with osteoarthritis together, including people who don’t get worse. We know that people’s age, sex and weight influence osteoarthritis progressing, but don’t tell us enough about personal risk. People with osteoarthritis want us to use tests rather than just personal information like age and weight alone to find the right treatments for them. Being able to test for the chance of getting worse would help target clinical trials of treatments at the people most likely to benefit. It would help people with knee osteoarthritis and their health professionals have a clearer picture about the future, allowing best treatment options to be offered early. Knee (synovial) fluid bathes the knee joint. Some proteins in knee fluid could be important markers of knee osteoarthritis that gets worse. The fluid being close to knee tissues gives more information than looking in blood alone. We can measure proteins (biological factors) in knee fluid and link these to what happens to the knee in the future, helping us to find new tests to pick out this group and develop targeted treatments. Aim: We want to identify new markers that link to knee osteoarthritis getting worse, or better, over time. Plan: We will follow people with early knee osteoarthritis, measuring changes in: 1) knee pain scores (including pain that doesn’t get better) 2) knee X-ray scores Four groups of people (‘cohorts’) with early knee osteoarthritis taking part in research will be followed for 2-5 years: 1) MenTOR, people with early knee osteoarthritis who had previous key-hole knee surgery 2) selecting people with early osteoarthritis from a larger international study called STEpUP OA (who already had 7000 proteins measured in their knee fluid) 3) STEP FORWARD-2, a new group with early knee osteoarthritis 4) individuals developing knee osteoarthritis in UK Biobank, a study of 500,000 people, some with 3000 proteins measured in blood samples We will study clinical and biological factors in knee fluid and blood together, linking protein markers with knee information over time, to see whether we can predict who gets worse or better. Relevance to patients: This study could transform the way we think about and treat knee osteoarthritis. Throughout the study, we will discuss our results with people with arthritis and how these should be developed into tests for use in trials or the clinic in the future. This work is vital to improve our understanding of how to personalise treatments for people with knee osteoarthritis based on their biological risk of getting worse. We need this information for successful clinical trials of new treatments which aim to prevent or reduce progression of knee osteoarthritis.
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