| Summary: | The purpose of this review is to evaluate the clinical and cost-effectiveness of hyaluronic acid (HA) relative to other knee osteoarthritis (OA) interventions, and to review evidence-based guidelines for the use of intra-articular (IA) hyaluronic acid (HA) for knee OA. There is a substantial body of evidence investigating viscosupplementation with hyaluronic acid (HA) in adults with knee osteoarthritis (OA), but the evidence to support its efficacy is conflicting. Three meta-analyses rated by investigators as the best available evidence suggested that HA was superior to intra-articular (IA) placebo, corticosteroids (CS), and non-steroidal anti-inflammatory drugs (NSAIDs), in terms of improving knee pain and function, without increasing adverse events. However, another study reported that when only the highest-quality randomized controlled trials (RCTs) were meta-analyzed, no clinically important differences of HA treatment over IA placebo were observed. There are significant limitations reported in the HA literature, including flawed study designs and reporting, a strong placebo effect from IA injections, potential conflicts of interest due to industry funding, and variation in dose, treatment course, and molecular composition of the various HA agents under study. It has been suggested that statistical significance of effects observed in some HA studies may not have clinical significance. Limited high-quality evidence suggests that two types of HA agents are cost-effective in the treatment of knee OA compared with other interventions including NSAIDS and other analgesics, as well as other forms of conservative care such as physiotherapy, weight loss, and ambulatory aids. The majority of guidelines did not find sufficient evidence to make a recommendation for or against the use of HA for knee OA, however two guidelines recommend against its use. Some guidelines recommend HA after failure of other treatments, or in older adults with a certain OA grade
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