Long-Term Efficacy of Carboxymethyl-Chitosan in Advanced Knee Osteoarthritis: A Twelve-Month Follow-Up Study on Non-Responders to Hyaluronic Acid

Background: Knee osteoarthritis (OA) is a prevalent degenerative joint disease characterized by the degeneration of joint cartilage. Knee OA leads to pain, stiffness, swelling, and decreased mobility, significantly impacting the quality of life of affected people. Advanced-stage osteoarthritis often necessitates surgical intervention due to poor response to conventional treatments, such as intra-articular hyaluronic acid (HA). Carboxymethyl-chitosan (CM-C), an emerging therapeutic agent, has shown potential in reducing inflammation, improving lubrication, and enhancing joint function. This study aimed to evaluate the long-term efficacy of CM-C injections in patients with advanced knee osteoarthritis, non-responders to HA. Methods: This retrospective study included 16 patients (mean age: 79.56 years) with Kellgren–Lawrence grade 3–4 knee OA treated with a single intra-articular injection of CM-C. Pain and functional outcomes were assessed using the Visual Analogue Scale (VAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline (T0), one month (T1), three months (T2), six months (T3), and twelve months (T4). Results: Significant pain reduction was observed at early follow up, (VAS: T1 p = 0.0002, T2 p = 0.0265; KOOS Pain: T1 p = 0.0014). However, pain partially returned by T3 and T4. KOOS activities of daily living (p = 0.0005), QoL (p = 0.0396), and Sport and Free Time (p = 0.0367) subscales showed significant improvement at T1, though worsening trends were observed in subsequent follow up with raw values suggesting persistent benefits. Strong negative correlations were found between VAS and KOOS subscales at various follow ups. Conclusions: A single CM-C injection demonstrated early pain relief and functional improvement in advanced knee OA for non-responders to HA. However, the long-term effects may diminish over time, necessitating a careful consideration of re-treatment strategies or combined therapies.