Intra-Articular Injections of Hyaluronic Acid or Steroids Associated With Better Outcomes Than Platelet-Rich Plasma, Adipose Mesenchymal Stromal Cells, or Placebo in Knee Osteoarthritis: A Network Meta-analysis

Purpose: To evaluate the clinical effects of hyaluronic acid (HA), steroids, platelet-rich plasma (PRP), or adipose mesenchymal stromal cell (MSC) injections in the treatment of knee osteoarthritis (OA). Methods: Randomized controlled trials with OA of the knee that compared HA, steroids, PRP, adipose MSC, or their combination with placebo or in head-to-head combination were identified from the MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS databases up to June 30, 2019. We performed a network meta-analysis of the relevant literature to determine whether there was benefit from HA, steroids, PRP, or adipose MSC treatment as compared with placebo. Results: A total of 43 trials covering 5554 patients were included. Steroids were ranked most likely to be effective for the management of pain or function, with adipose MSC and multiple PRP appearing least likely to be effective. Although no significant difference was observed among the 6 interventions, except for single PRP with respect to adverse effects, steroids and HA exhibited a lower rate of AEs compared with the placebo. In view of severe adverse effects, only single PRP was superior to placebo. Direct pairwise meta-analysis for pain relief showed that HA was superior to placebo or single PRP, but steroids had a significantly worse effect than single PRP. In addition, direct pairwise meta-analysis for adverse effects favored steroids in comparison to HA. Conclusions: The ranking statistics like surface under the cumulative ranking curve values of our network meta-analysis support the use of steroids and HA for appropriate patients with knee OA. For pain relief and AEs, steroids are most likely the best treatment, followed by HA. Single PRP, multiple PRP, and adipose MSC interventions do not result in a relevant reduction of joint pain nor improvement of joint function compared with placebo. However, treatment effect differences were small and potentially not clinically meaningful, indicating that other factors, such as cost and patient preferences, may be more important in patients with knee OA.