2015 ISAKOS Biennial Congress ePoster #206
The Effect of Intra-Articular High-Molecular-Weight Hyaluronic Acid on Osteoarthritis of the Knee
Hiroyuki Onuma, MD, PhD, Kawasaki, Kanagawa JAPAN
Toshihiro Sugihara, MD, PhD, Kawasaki, Kanagawa JAPAN
Moroe Beppu, MD, PhD, Setagaya-ku, Tokyo JAPAN
International University of Health and Welfare Hospital, Nasushiobara-shi, Tochigi, JAPAN
The FDA has not cleared the following pharmaceuticals and/or medical device for the use described in this presentation. The following pharmaceuticals and/or medical device are being discussed for an off-label use: Seikagakukougyou, Purified Sodium Hyaluronate; Tyugaiseiyaku, Purified Sodium Hyaluronate
Summary: We compared the efficacy and safety of injection of different average molecular weights hyaluronan products of 900,000 and 1,900,000 in patients with knee osteoarthritis. There was a clinically meaningful and statistically significant improvement in the clinical outcomes of both AMW as compared to baseline. However no clear differences among two products preparations were found in their outcomes.
The currently available major hyaluronan products used in conservative therapy for osteoarthritis (OA) of the knee are three sodium hyaluronic acid (HA) medical products, Artz(®), Suvenyl(®) and a chemically modified derivative of sodium HA Synvisc(®). HA with a molecular weight of approximately 600,000-6,000,000 is reportedly effective against OA. Therefore, HA with higher molecular weight is expected to be more effective against OA. Two initially used in Japan have different average molecular weights (AMW) of 900,000 and 1,900,000. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products.
The objectives of this study were to compare the efficacy and safety of injection of different AMW hyaluronan products of 900,000 and 1,900,000 in patients with knee OA. METHODS: A randomized trial. Patients with OA of the knee were randomized. In 40 patients, 40 knees were treated 5 or more weekly with HA injection, and were followed for more than 5 weeks after the initial injection. Before every injection the synovial fluid was obtained by arthrocentesis. The clinical symptoms were evaluated using the Japanese knee osteoarthritis measurement (JKOM) used for measuring patient-based outcomes and health-related quality of life and pain visual analog scale (VAS). The 22 patients (mean age 66.2 years) were treated with the 900,000-AMW HA product (Artz(®), Seikagaku Corp.) and the 18 patients (mean age 63.7 years) were treated with the 1,900,000-AMW HA product (Suvenyl(®), Chugaiseiyaku Corp.). Clinical and radiographic evaluation was performed, including examination of the patient's function. All patients had knee OA as determined by Kellgren-Lawrence (K-L) grade 1 to 3. We had no patient with K-L grade 4. All patients were questioned regarding any adverse events during treatment. We had two subgroups. The subgroup 1 is K-L grade 1 to 3. The subgroup 2 consisted of patients with joint fluid under 5ml, and over 5ml to 20ml before injection. Differences in outcome were analyzed with student t tests, Bonferroni, Mann-Whitney U test and Wilcoxon signed rank test.
There was a clinically meaningful and statistically significant improvement in the clinical outcomes of both AMW as compared to baseline, especially VAS of both AMW at Week 3 to 5, JKOM of both HMW at Week 5. The gate pain of patients treated with the 1,900,000-AMW HA product was significantly improved a week after initial injection. However no clear differences among two products’ preparations were found in their outcomes. The evaluable subgroup 1 consisted of large portion of patients with K-L grade 2 whose VAS was significantly improved. The subgroup of patients with joint fluid over 5ml to 20ml was significantly improved at baseline. No differences between groups were observed with respect to incidence of adverse events.
Our findings indicate that the 1,900,000-AMW HA product might earlier show the effectiveness than 900,000-AMW HA product, however two AMW hyaluronan products are safe and seem to be effective in the treatment of mild and moderate OA of the knee without clear differences among two products’ preparations in the clinical outcomes. I have no financial conflicts to disclose. This study of the Ethical Review Board was approved. (KF-2-0805-048)
The FDA has cleared the Artz(®) (Supartz) of two pharmaceuticals for the use described in this presentation.