Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: a systematic review and meta-analysis

Semin Arthritis Rheum. 2014 Apr;43(5):593-9. doi: 10.1016/j.semarthrit.2013.10.002. Epub 2013 Oct 14.


Objective: To assess the relative efficacy of intra-articular hyaluronic acid (IAHA) in comparison with non-steroidal anti-inflammatory drugs (NSAIDs) for knee osteoarthritis (OA).

Methods: We searched Medline, EMBASE, Google Scholar, ISI Web of Science, and Cochrane Database from inception until February 2013. Randomized controlled trials comparing HA with NSAIDs for knee OA were included if they reported at least one pain outcome. Two reviewers abstracted data and determined quality. Outcomes included pain, function, and stiffness. Random-effects meta-analyses were performed.

Results: Five trials (712 participants) contributed to the pain analysis. Both groups showed improvement from baseline. The analysis found an effect size (ES) of -0.07 (95% CI: -0.24 to 0.10) at trial end, favoring neither treatment. There were no statistically significant differences between the groups at 4 and 12 weeks in function [ES = -0.08 (95% CI: -0.39 to 0.23)] or stiffness [ES = 0.03 (95% CI: -0.27 to 0.34)] analyses based on two trials. Injection site pain was the most common adverse event reported in the HA group, and gastrointestinal adverse events were more common in the NSAIDs group.

Conclusion: This meta-analysis suggests that IAHA is not significantly different from continuous oral NSAIDs at 4 and 12 weeks. Our study detected no safety concerns; however, the included trials had only a short follow-up duration. Given the favorable safety profile of IAHA over NSAIDs, this result suggests that IAHA might be a viable alternative to NSAIDs for knee OA, especially for older patients at greater risk for systemic adverse events.

Keywords: Knee osteoarthritis; NSAIDs; Osteoarthritis; Treatment.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Humans
  • Hyaluronic Acid / therapeutic use*
  • Injections, Intra-Articular
  • Osteoarthritis, Knee / drug therapy*
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Hyaluronic Acid