Intraarticular Hyaluronic Acid Preparations for Knee Osteoarthritis: Are Some Better Than Others?

Abstract

Objective This literature review summarizes evidence on the safety and efficacy of intraarticular hyaluronic acid (IAHA) preparations approved in the United States for the treatment of osteoarthritis of the knee. Design A systematic literature search was performed in PubMed, Ovid MEDLINE, and SCOPUS databases. Only studies in which clinical outcomes of individual IAHA preparations alone could be assessed when compared to placebo, no treatment, other standard knee osteoarthritis treatments, and IAHA head-to-head studies were selected. Results One hundred nine articles meeting our inclusion criteria were identified, including 59 randomized and 50 observational studies. Hylan G-F 20 has been the most extensively studied preparation, with consistent results confirming efficacy in placebo-controlled studies. Efficacy is also consistently reported for Supartz, Monovisc, and Euflexxa, but not for Hyalgan, Orthovisc, and Durolane. In the head-to-head trials, high-molecular-weight (MW) Hylan G-F 20 was consistently superior to low MW sodium hyaluronate preparations (Hyalgan, Supartz) up to 20 weeks, whereas one study reported that Durolane was noninferior to Supartz. Head-to-head trials comparing high versus medium MW preparations all used Hylan G-F 20 as the high MW preparation. Of the IAHA preparations with strong evidence of efficacy in placebo-controlled studies, Euflexxa was found to be noninferior to Hylan G-F 20. There are no direct comparisons to Monovisc. One additional IAHA preparation (ie, Synovial), which has not been assessed in placebo-controlled studies, was also noninferior to Hylan G-F 20. Conclusion IAHA efficacy varies widely across preparations. High-quality studies are required to assess and compare the safety and efficacy of IAHA preparations.

Assessment of the Response Profile to Hyaluronic Acid Plus Sorbitol Injection in Patients with Knee Osteoarthritis: Post-Hoc Analysis of a 6-Month Randomized Controlled Trial

“…One of the potential confounding factors potentially impacting OA response is compliance, however, this is not relevant here given the specific modalities of HA treatment (given once at baseline). Moreover, the responder profile observed in the present study could not be extrapolated to other HA products since it has been shown that HA efficacy varies widely across preparations [16]. It should also be pointed out that our population included mainly patients with mild to moderate OA and, consequently, our results could not be extrapolated to severe OA.…”

EUROVISCO Good Practice Recommendations for a First Viscosupplementation in Patients with Knee Osteoarthritis

“…All the clinical trials performed with currently licensed products have demonstrated these 3 effects, although the magnitude of the response can vary from one to another. 19 They were also of the opinion that due to its analgesic effect it could delay surgery without being able to arrest the degenerative process and prevent surgery in the long term.…”

“…16,17 Despite this, however, a few societies still do not recommend the use of HA injections, mainly due to a level of evidence considered insufficient. They maintain that the heterogeneity of the studies fails to provide unquestionable evidence in favor of VS. 18 The heterogeneity of the results may be related to differences in the efficacy of products containing HA, 19 likely due to wide differences between one product and another in terms of molecular weight, concentration, volume injected, intra-articular residence time, and viscoelasticity. The profile of the patient population may also greatly influence the result of VS as in the case of obesity and advanced radiological grade, which have both been identified as independent factors for poor response to VS. 20 At the last line of the manuscript the European Viscosupplementation Consensus Group, EUROVISCO, therefore examined the individual factors that may influence the decision to perform VS in a patient consulting for painful OA of the knee.…”

A comprehensive review of intraarticular knee injection therapy, geniculate injections, and peripheral nerve stimulation for knee pain in clinical practice

“…The most studied preparation of intraarticular hyaluronic acid (IAHA) is Hylan G-F 20 which has showed consistent results confirming efficacy in placebo-controlled studies. 74 A comprehensive review of intraarticular knee injection therapy, geniculate injections, and peripheral nerve stimulation...…”