Efficacy and safety of repeated courses of hyaluronic acid injections for knee osteoarthritis: A systematic review

Introduction: Hyaluronic acid (HA) is a commonly prescribed intra-articular (IA) therapy for knee osteoarthritis (OA). While a single series of IA-HA has been well studied, the efficacy and safety of repeated courses of IA-HA injection therapy in knee OA patients have not been evaluated as frequently. Methods: A literature search was conducted using MEDLINE, EMBASE and PubMed databases. The primary outcome measure was knee pain reduction after each treatment course and/or last reported follow-up visit. Secondary outcomes were treatment-related adverse events (AEs) and serious adverse events (SAEs). Results: A total of 17 articles (7 RCTs and 10 cohort studies) met the pre-defined inclusion criteria. Of the RCTs, six were double-blind with two trials including open label extension studies, and one was singleblind. Studies ranged from investigating a single reinjection cycle to four repeat injection cycles. Eleven studies evaluated one reinjection, five studies evaluated >= 2 repeated courses of IA-HA, and one study allowed either one or two repeated courses. All studies reported pain reduction from baseline in the IA HA treatment group throughout the initial treatment cycle, and either sustained or further reduced pain throughout the repeated courses of treatment. The study with the longest follow-up repeated IA-HA injection every 6 months for 25 months. Pain decreased after the first course and continued to decrease until the end of the study, with an approximate 55% reduction in pain compared to baseline. Common AEs were joint swelling and arthralgia; there were no reported SAEs. All repeated courses were well tolerated, and the number of documented AEs and SAEs was similar to the primary injection regimens. Conclusion: Repeated courses of IA-HA injections are an effective and safe treatment for knee OA. Repeat courses were demonstrated to maintain or further improve pain reduction while introducing no increased safety risk. (C) 2018 The Authors. Published by Elsevier HS journals, Inc.