Comparative Effectiveness of Alternative Dosing Regimens of Hyaluronic Acid Injections for Knee Osteoarthritis: A Systematic Review

Abstract

Context: Viscosupplementation is widely used for management of knee osteoarthritis. Many formulations of hyaluronic acid (HA) are available, ranging from a single injection to a series of up to 5 injections per treatment. Objective: To compare efficacy between single and multiple HA injection formulations. Data Sources: MEDLINE, EMBASE, Cochrane, Web of Science, Scopus databases were all searched. Study Selection: Full-text prospective randomized and nonrandomized controlled human trials, cohort studies, and cost-effectiveness evaluations in the English language comparing different injection regimens of viscosupplementation were included. Study Design: Systematic review. Level of Evidence: Level 1. Data Extraction: Data were collected using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Four databases were searched by a librarian and the principal investigator, identifying 6196 articles for screening. Results: Eleven studies met the inclusion criteria. Of the studies comparing single- with multiple-injection formulations of HA for treatment of knee osteoarthritis, there was no consistent difference in patient-reported outcomes. Furthermore, 5-injection formulations do not appear to be superior to 3-injection formulations. Conclusion: There are limited head-to-head trials comparing viscosupplementation formulations that differ based on number of injections, and in particular, there is a paucity of trials evaluating single-injection formulations. Based on the currently available data, there appears to be similar efficacy with the possibility for greater cost-effectiveness and less patient inconvenience with single-injection formulations.

Should intra‐articular hyaluronic acid be used routinely for knee osteoarthritis pain?

“…The numerous FDA‐approved IA‐HA formulations vary in terms of their administration. Several require a series of three or even five injections typically spaced 1 week apart, incurring further burden on the patient as well as cost 23 . There is general concern regarding the cost effectiveness of IA‐HA injections.…”

A Comprehensive Review of Viscosupplementation in Osteoarthritis of the Knee

“…39,40 The comparative efficacy of single-injection HA products has mixed results in the literature and requires further investigation. [48][49][50][51] HYALURONAN BACKGROUND Hyaluronan (HA) is a high-molecular-weight extracellular matrix (ECM) polysaccharide and hyaluronic acid derivative, particularly in soft connective tissues. 52 It has various functions in development, growth, and tissue regeneration.…”

“…Given these varying results, further systematic analyses are needed to explore the use of single-injection HA products. 50…”

New Viscoelastic Hydrogel Hymovis MO.RE. Single Intra-articular Injection for the Treatment of Knee Osteoarthritis in Sportsmen: Safety and Efficacy Study Results

“…In that study, (Concoff et al, 2017;Altman et al, 2018), making the treatment more attractive, and increasing compliance. Further advantages of a single injection involve reducing the treatment burden and costs for patients (McElheny et al, 2019), including time away from work or training because of the need for fewer transfers to medical facilities and reduced recovery time. The procedure, requiring 3-day of rest, represents a chance for regular sports players who need to keep absence from sports activity to a minimum.…”