Differentiating factors of intra-articular injectables have a meaningful impact on knee osteoarthritis outcomes: a network meta-analysis

Knee Surg Sports Traumatol Arthrosc. 2020 Sep;28(9):3031-3039. doi: 10.1007/s00167-019-05763-1. Epub 2020 Jan 3.


Purpose: There are a number of developments in intra-articular therapies that have been determined to be differentiating factors within the classes of treatments. This study evaluated the efficacy and safety of intra-articular treatments of primary knee osteoarthritis in the short term (3 months follow-up), using a network meta-analysis design, while taking within-class differentiating factors into consideration.

Methods: A literature search of MEDLINE (through OVID), EMBASE (through OVID), Cochrane Central Register of Controlled Trials for all trials comparing intra-articular therapies was conducted on November 12, 2018. The treatments assessed were high molecular weight and low molecular weight hyaluronic acid injections, extended-release corticosteroids, standard-release corticosteroids, platelet-rich plasma, and saline. A frequentist network meta-analysis was conducted for each outcome.

Results: Sixty-four articles (9710 patients) met the inclusion criteria. High molecular weight hyaluronic acid (- 0.53, 95% CI - 0.81 to - 0.25) and PRP (- 0.79, 95% CI - 1.32 to - 0.26) were the only treatments with a confidence interval that lay completely above the MID threshold; however, PRP results varied within sensitivity analyses. For the function analysis, high molecular weight hyaluronic acid (SMD - 0.76, 95% CI - 1.30 to - 0.22) was the only treatment with a confidence interval entirely above the MID. Extended-release corticosteroid demonstrated a possible benefit in functional improvement (SMD - 0.98, 95% CI - 1.79 to - 0.17) compared to that of standard-release corticosteroid (SMD - 0.14, 95% CI - 0.72 to 0.44).

Conclusion: High molecular weight HA was the only treatment to surpass the MID for both pain and function outcomes. Extended-release corticosteroids may provide additional clinical benefit over standard-release corticosteroids. Platelet-rich plasma demonstrated possibly beneficial results; however, wide confidence intervals and sensitivity analyses made the conclusions of efficacy uncertain.

Level of evidence: Level 1. Systematic review of level 1 evidence.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Delayed-Action Preparations
  • Glucocorticoids / therapeutic use
  • Humans
  • Hyaluronic Acid / therapeutic use
  • Injections, Intra-Articular
  • Network Meta-Analysis
  • Osteoarthritis, Knee / therapy*
  • Platelet-Rich Plasma
  • Saline Solution


  • Delayed-Action Preparations
  • Glucocorticoids
  • Saline Solution
  • Hyaluronic Acid