Comparative safety profile of hyaluronic acid products for knee osteoarthritis: a systematic review and network meta-analysis

• Published in: Osteoarthritis and cartilage Vol. 24; no. 12; pp. 2022 - 2041
• Main Authors: Bannuru, Raveendhara R., MD, PhD, FAGE, Osani, Mikala, BA, Vaysbrot, Elizaveta E., MD, MS, McAlindon, Timothy E., MD, MPH
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2016
• Subjects: Aged; Bayes Theorem; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Intra-articular therapy; Knee; Male; Middle Aged; Network Meta-Analysis; Osteoarthritis; Osteoarthritis, Knee; Rheumatology; Safety; Knee; Intra-articular therapy; Safety; Hyaluronic acid; Osteoarthritis
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2016.07.010

Summary Purpose Intra-articular (IA) hyaluronic acid (HA) is considered a safer alternative to oral NSAIDs and opioids for knee osteoarthritis. A recent review raised potential safety concerns about HA, warranting further review of safety outcomes. We examined the risks of HA compared with IA placebo and investigated whether the risks vary among individual HA preparations. Methods We searched all relevant databases from inception to October 2015 and sought unpublished data. We included all knee osteoarthritis trials which compared any of the 18 HA products and reported on adverse events and withdrawals. We calculated Odds Ratios for safety data reported at the longest follow-up. Network meta-analysis was performed using a Bayesian hierarchical random effects model for mixed multiple treatment comparisons. Results We identified 74 studies involving 13,032 participants aged between 45-75 years. The proportion of women ranged from 28% -100%. The overall incidence of local reactions reported across all products was 8.5%. Commonly reported adverse events were transient local reactions, such as pain, swelling and arthralgia, which subsided rapidly. None of the HA products were statistically significantly different from IA placebo or from each other with regard to incidence of adverse events. Three treatment-related serious adverse events were reported among 9,214 participants. Conclusions Given the very low incidence of any particular adverse events, we conclude that HA products are relatively well tolerated. These products have a similar safety profile compared to each other. This information along with the comparative effectiveness profile and relative cost would be helpful for clinicians in delivering individualized patient care.