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Researchers at NDORMS have identified four subgroups of knee osteoarthritis which will improve patient treatment and drug development.

The study, led by Dr Maja Radojčić, Postdoctoral Researcher at NDORMS examined pain trajectories of patients with knee osteoarthritis (OA), a chronic joint disease that limits function and affects quality of life. Knee OA has generally been thought of as a heterogeneous disease with treatment options focusing on pain management or the surgical option of joint replacement.

However, by measuring patients’ pain experience, functional limitation, and responsiveness to available treatment options over time, the team were able to categorise patients into four different phenotypes: low-fluctuating, mild-increasing, moderate-treatment-sensitive and severe-treatment-insensitive pain. Importantly, the group in need of novel options not responsive to current treatments was found, as well as a subgroup that significantly improved after surgery.

Maja said: “Our results will help inform clinicians about symptom development and open the way to focus on more targeted personalised treatments for OA patients.”

“It has previously been thought that some patients might have good joint functionality despite severe pain,” she continued. “But we mapped dual trajectories to investigate the interplay between pain and functional limitation over time and showed that they go hand-by-hand, developing the same pattern or patients not distinguishing them.”

The significance of findings for the clinical trial design stressed co-author Professor Nigel Arden. “Selecting patients who are most in need and likely to benefit from a specific treatment option, as well as not selecting those unlikely to progress over years or responding to placebo will help OA clinical trials to reach endpoints.”

The personalised medicine in OA has been identified as a need by the research community, but except theoretical concept underpinned by assumptions about different processes involved, there has not been a phenotyping work to support it. The senior author Dr Stefan Kluzek said: “Our research showed for the first time presence of clinical phenotypes of knee OA, which are reproducible between studies and share some common characteristics.” He continued: “Different responsiveness of each group to current treatments is of paramount importance to our understanding of the most effective clinical pathways but also suggests diverse molecular mechanisms underlying osteoarthritis.”

The research was funded by Versus Arthritis, as a work package of the Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, and supported by the OAI study.

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