Summary

A comparison of clinical outcomes and duration of effects of trehalose hyaluronic acid (THA) with standard non-trehalose hyaluronic acid (NT-HA) administered as infiltrative therapy in patients with symptomatic osteoarthritis of the knee.

Abstract

Background

Osteoarthritis (OA) is one of the most prevalent degenerative joint disease with a worldwide burden that continue to increase. It is a multifactor, complex pathology that ultimately lead to joint degeneration. Inflammatory cytokines (e.g. IL-1ß, TNFa) are released after a trauma increasing ROS production, therefore creating a persistent oxidative stress. That is why, reducing the oxidative stress should be the target treatment in OA. Hyaluronic acid (HA) has been used as an infiltrative therapy in OA because one of its properties, to decrease ROS synthesis in the synovial liquid and also to prevent oxidative stress induced by inflammatory cytokines. However, one of the weaknesses is its rapid clearance following intra-articular injection. This effect could be reduced with HA stabilizing agents such as sugars, polyols, amino acids, and salts.

Purpose

To compare clinical outcomes of trehalose hyaluronic acid (THA) with
standard non-trehalose hyaluronic acid (NT-HA) and to evaluate which one provides
longer-lasting effects when administered as infiltrative therapy in patients with
symptomatic OA of the knee.

Methods

This is a controlled trial with parallel arms in which 60 patients with OA were randomized to trehalose- hyaluronic acid (T-HA) or non-trehalose hyaluronic acid (NT-HA) groups. The study was blinded for participants, physicians and examiner. HA administration consisted of 3 doses to every patient in 15 intervals, with a follow-up at 3 (T1) and 6 (T2) months. The treatment efficacy was measured with the International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS). Outcomes were compared with basal scores and between the treatments. For safety evaluation, any adverse reaction was recorded during the study.

Results

From 155 patients assessed for eligibility, seventy-five were included in the
study. Thirty-eight were randomized into group A and thirty-seven into group B to obtain the desired sample of 60 patients (30 per group). The mean age was 56.4 ± 15.6 years. At 3 months, IKDC, KOOS, and VAS improved for both groups (P < .05). Median [IQR] IKDC improved from 57.47 [49.43 - 62.64] to 65.16 [56.9 - 79.02] and from 52.87 [45.98 - 57.9] to 67.48 [53.00 - 75.75] respectively. At 6 months, group T-HA continued to improve IKDC, KOOS, and VAS (P < .05), while group NT-HA scores decreased (P < .05). IKDC increased to 66.98 (60.92-78.79) for T-HA, while it decreased to 59.77 (35.34-73.03) for NT-HA. No significant adverse events were registered with either of the formulations.

Conclusions

Both hyaluronic acids are safe and provide a relief in osteoarthritic knee symptoms and function. T-HA reduces early OA symptoms such as pain and loss of function and provides a longer-lasting result compare to NT-HA in symptomatic knee OA.