Clinical Question: Are intraarticular injections of hyaluronic acid (Synvisc) effective for osteoarthritis of the knee?

Setting: Outpatient (specialty)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: In a previous meta-analysis (Lo GH, et al. Intraarticular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA December 17, 2003;290:3115–21), investigators found that the use of intraarticular injections of hyaluronic acid to manage osteoarthritis of the knee was minimally effective at best, while a recent Cochrane Review (Bellamy N, et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev 2005; (2):CD005321; whose authors received funding from the manufacturer) found these injections to be much more effective. Arrich and colleagues examined the same question but differed from the previous two analyses by examining separate outcomes (i.e., pain at rest, pain during exercise, and function) rather than grouping them together. The current study was sponsored by a national insurance program in Austria.

After a careful literature search, the authors included 22 randomized controlled trials. The study quality was generally poor: only seven used concealed allocation; six presented usable data from an intention-to-treat analysis; 16 had blinded outcome assessment; and only four did all of these aspects correctly. Eight studies with a total of 468 patients reported 10 outcomes for pain at rest at two to six weeks. Six of 10 did not demonstrate any benefit; one poorly designed, industry-sponsored study reported a large benefit for 20 and 40 mg. There was too much heterogeneity to combine studies, and poorer quality trials tended to find a greater benefit. Nine studies with 1,141 patients reported 10 outcomes for pain during exercise. Pooled data at 10 to 14 weeks and at 20 to 30 weeks found a statistically—but probably not clinically—significant benefit. Hyaluronic acid had no significant effect on function at any time. In the previous analysis by Lo and colleagues, 17 of 22 trials were found to be industry sponsored.

Bottom Line: The evidence that intraarticular hyaluronic acid helps patients with knee osteoarthritis is of poor quality. Improvements in pain at rest and pain during exercise are seen in a minority of studies, and those studies are of lower quality than those showing no benefit. There is no evidence of functional improvement. Injections such as this have a potentially powerful placebo effect, so any benefit seen in studies without concealed allocation is likely to represent the placebo effect rather than any effect of the drug. (Level of Evidence: 1a–)