Intra-Articular Use of Hyaluronic Acid Preparations in the Treatment of Knee Osteoarthritis

Abstract

Purpose of the study The knee is the most common peripheral site of osteoarthritis (KOA; knee osteoarthritis). The mainstay of non-operative treatment is education, exercise, weight reduction, and pharmacological therapy. Intra-articular hyaluronic acid (HA) injection is a nonoperative treatment option. The aim of our study was to assess the most recent data on the efficacy of intraarticular administration of HA in KOA therapy and to compare it with intraarticular injections of platelet-rich plasma (PRP), corticosteroids (CS) and placebo (saline solution). Material and methods The PubMed and Cochrane Library databases were searched for randomized clinical trials (RCTs) conducted between 2012 and 2023 comparing the efficacy of HA with PRP, CS, or placebo. The efficacy was mostly assessed using the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) and VAS (Visual Analogue Scale) for pain. The Rob2 (Risk of Bias 2) tool developed by the Cochrane Collaboration was used to assess the risk of bias. Results The data pooled from 29 studies (2032 patients treated with HA, 965 with PRP, 376 with CS and 697 with placebo) were analysed. The efficacy was assessed mostly at 1, 3, 6 and 12 months after the administration of the investigated substance. All types of interventions (HA, PRP, CS) were found to have a beneficial effect on the knee affected by KOA, namely through symptom relief. The greatest effect was achieved with PRP, which lasted longer than that of HA or CS. HA offered a moderate relief of symptoms, which was still apparent at 6 months after administration. The administration of CS resulted in a rapid onset of pain relief which was, however, of short duration and started to diminish as early as after the first month of follow-up. In placebo-controlled studies, the follow-up did not exceed 6 months. Discussion and Conclusions Intra-articular administration of HA continues to be the most common intra-articular therapy for patients with KOA. We should therefore take an interest in its outcomes. This intervention is recommended by the OARSI as 1B level treatment. The ACR, on the contrary, has turned from both the HA and PRP. The NICE in its opinion on non-surgical management of KOA also advises against HA. In our study, on the other hand, we concluded that all three active pharmaceutical ingredients (HA, PRP and CS) improved the KOA symptoms, with PRP showing the most significant, longest lasting and most consistent overall beneficial effects. This conclusion does not imply that HA offers no or only negligible effect. The particular size of effect of intraarticular administration of HA depends on a number of circumstances. Further research should therefore be conducted which would look into the HA benefit in relation to the specific patient, KOA phenotype, stage of inflammation, or healing processes.