Is Local Viscosupplementation Injection Clinically Superior to Other Therapies in the Treatment of Osteoarthritis of the Knee: A Systematic Review of Overlapping Meta‐analyses

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Abstract
Purpose: To conduct a systematic review of overlapping meta‐analyses comparing treatment of knee osteoarthritis (OA) with intra‐articular viscosupplementation (intra‐articular hyaluronic acid [IA‐HA]) versus oral nonsteroidal anti‐inflammatory drugs (NSAIDs), intra‐articular corticosteroids (IA‐corticosteroids), intra‐articular platelet‐rich plasma (IA‐PRP), or intra‐articular placebo (IA‐placebo) to determine which meta‐analyses provide the best current evidence and identify potential causes of discordance. Methods: Literature searches were performed for meta‐analyses examining use of IA‐HA versus NSAIDs, IA‐corticosteroids, IA‐PRP, or IA‐placebo. Clinical data were extracted, and meta‐analysis quality was assessed. The Jadad algorithm was applied to determine which meta‐analyses provided the highest level of evidence. Results: Fourteen meta‐analyses met the eligibility criteria and ranged in quality from Level I to IV evidence. In studies reporting patient numbers, there were a total of 20,049 patients: 13,698 receiving IA‐HA, 355 receiving NSAIDs, 294 receiving IA‐corticosteroids, and 5,702 receiving IA‐placebo. Ten studies examined the effects of IA‐HA versus IA‐placebo; of these, 5 found that IA‐HA improved pain and 4 found that IA‐HA improved function. No clinically relevant differences in the efficacy of IA‐HA versus NSAIDs regarding pain and function were found. Regarding IA‐HA versus IA‐PRP, IA‐HA improved knee function at 2 and 6 months after injection but the effects were less robust than those of IA‐PRP. Regarding IA‐HA versus IA‐corticosteroids, the positive effects of IA‐HA were greater at 5 to 13 weeks and persisted for up to 26 weeks. After application of the Jadad algorithm, 2 concordant high‐quality meta‐analyses were selected and both showed that IA‐HA provided clinically relevant improvements in pain and function compared with IA‐placebo. Conclusions: This systematic review of overlapping meta‐analyses comparing IA‐HA with other nonoperative treatment modalities for knee OA shows that the current highest level of evidence suggests that IA‐HA is a viable option for knee OA. Its use results in improvements in knee pain and function that can persist for up to 26 weeks. IA‐HA has a good safety profile, and its use should be considered in patients with early knee OA. Level of Evidence: Level IV, systematic review of Level I to IV studies.

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