A Cochrane review [Abstract] 1 included 76 studies. Follow-up periods varied between day of last injection and 18 months. Forty trials included comparisons of hyaluronan/hylan and placebo, 10 trials included comparisons of intra-articular (IA) corticosteroids, 6 trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), 3 trials included comparisons of physical therapy, 2 trials included comparisons of exercise, 2 trials included comparisons of arthroscopy, 2 trials included comparisons of conventional treatment, and 15 trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses.
In a systematic review and meta-analysis of randomised trials 2, 169 trials provided data on 21 163 randomised participants. Evidence of small study effects and publication biases was observed for pain and function. Twenty four large, placebo controlled trials (8997 randomised participants) included in the main analysis of pain indicated that viscosupplementation was associated with a small reduction in pain intensity compared with placebo (SMD −0.08, 95% CI −0.15 to −0.02), with the lower bound of the 95% CI excluding the minimal clinically important between group difference. This effect corresponded to a difference in pain scores of −2.0 mm (95% Ci −3.8 to −0.5 mm) on a 100 mm visual analogue scale. Trial sequential analysis for pain indicated that since 2009 there has been conclusive evidence of clinical equivalence between viscosupplementation and placebo. Similar conclusions were obtained for function. Based on 15 large, placebo controlled trials on 6462 randomised participants, viscosupplementation was associated with a statistically significant higher risk of serious adverse events than placebo (RR 1.49, 95% CI 1.12 to 1.98).
Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies) and by potential reporting bias.
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