By Lynda Williams
Intra-articular injections of hyaluronic acid offer a small, clinically irrelevant decrease in osteoarthritis knee pain at the risk for serious adverse events, suggest the results of a review and meta-analysis.
"The administration of these preparations should be discouraged," say Peter Jüni (University of Bern, Switzerland) and co-authors after examination of data from 89 trials including 12,667 patients between 1966 and 2012.
Data from 71 trials including 9617 patients indicated that viscosupplementation is associated with a moderate reduction in pain, with an effect size of ‑0.37, which equaled the prespecified effect for minimal clinical importance, but there was significant heterogeneity between trials.
Size, publication status, and use of blinded outcome status all significantly influenced the extent of pain reduction, the team notes in the Annals of Internal Medicine.
Data from five unpublished trials including 1149 patients had a null effect (‑0.03), while 18 larger trials including 5094 patients that used blinded outcome assessment had an effect size of ‑0.11, denoting a clinically irrelevant effect.
Data from 52 trials including 7904 patients indicated that viscosupplementation had a moderate effect on physical function (‑0.33), with a moderate between-trial heterogeneity. Data from 15 large trials with 4296 patients with blinded outcome showed an overall effect size of ‑0.09.
Results from six trials with 811 patients demonstrated a nonsignificant trend toward an increased risk for flare-ups (relative risk [RR]=1.51).
Moreover, a significant risk for serious adverse events, such as inpatient hospitalization, prolonged hospitalization, or persistent and significant disability, was indicated by data from a further 14 trials including 3667 patients (RR=1.41).
Viscosupplementation was also associated with an increased risk for trial dropout due to adverse events (RR=1.33) and local adverse events (RR=1.34) compared with sham treatment.
"Not only did we not find clinically relevant benefits of viscosupplementation, we also saw concerning safety signals compared with placebo," the team concludes.
"The increased risk in serious adverse events associated with viscosupplementation is particularly concerning, but causal mechanisms are unclear," they note.
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