Meta-analysis: Rheumatology

Knee osteoarthritis: Intra-Articular Injections of Platelet-Rich Plasma, Adipose Mesenchymal Stem Cells, and Bone Marrow Mesenchymal Stem Cells Associated with Better Outcomes Than Hyaluronic Acid and Saline 
 
The purpose of this work was to perform a network meta-analysis to evaluate clinical efficacy and treatment-related adverse events (AEs) of intra-articular hyaluronic acid (HA), leukocyte-poor platelet-rich plasma (LP-PRP), leukocyte-rich platelet-rich plasma (LR-PRP), bone marrow mesenchymal stem cells (BM-MSCs), adipose mesenchymal stem cells (AD-MSCs), and saline (placebo) during 6 and 12 months of follow-up. 
 
Six databases were searched for randomized controlled trials. Outcome assessments included the VAS score, WOMAC pain subscore, WOMAC score, IKDC subjective score, and treatment-related AEs. Forty-three studies meeting the eligibility criteria were included. Of these, two level I trials (Wu et al 2018; Lin et al. 2019) were conducted with RegenPRP. 
 
At 6 months, VAS scores and WOMAC pain subscores showed that AD-MSCs were the best treatment option. According to WOMAC scores and subjective IKDC scores, LP-PRP was the most effective treatment. At 12 months, only AD-MSCs were associated with improved VAS scores compared with the placebo. Both LP-PRP and AD-MSCs were more beneficial than the placebo for improving WOMAC pain subscores. LP-PRP and LR-PRP were significantly associated with improved WOMAC scores compared with the placebo after sensitivity analysis. LP-PRP exhibited relatively better efficacy in improving subjective IKDC scores than the placebo. 
 
Regarding safety, all treatments except for LP-PRP increased treatment-related AEs compared with the placebo. 
 
The authors concluded that during 6 months of follow-up, AD-MSCs relieved pain the best; LP-PRP was most effective for functional improvement. During the 12-month follow-up, both AD-MSCs and LP-PRP showed potential clinical pain relief effects; functional improvement was achieved with LP-PRP. Considering the evaluation of treatment-related AEs, LP-PRP is the most advisable choice. 
 
Level of Evidence: Level II, meta-analysis of Level I and II studies. 
 
Zhao D, Pan JK, Yang WY, Han YH, Zeng LF, Liang GH, Liu J. Intra-Articular Injections of Platelet-Rich Plasma, Adipose Mesenchymal Stem Cells, and Bone Marrow Mesenchymal Stem Cells Associated with Better Outcomes Than Hyaluronic Acid and Saline in Knee Osteoarthritis: A Systematic Review and Network Meta-analysis. Arthroscopy. 2021 Jul;37(7):2298-2314.e10. doi: 10.1016/j.arthro.2021.02.045. Epub 2021 Mar 10. PMID: 33713757 . 
 
Hohmann E. Editorial Commentary: Injection of Platelet-Rich Plasma Appears Superior to Hyaluronic Acid and Adipose- or Bone-Derived Marrow Stem Cells for Knee Osteoarthritis. Arthroscopy. 2021 Jul;37(7):2315-2317. doi: 10.1016/j.arthro.2021.03.053. PMID: 34226015. 
 
Migliorini F, Driessen A, Quack V, Sippel N, Cooper B, Mansy YE, Tingart M, Eschweiler J. Comparison between intra-articular infiltrations of placebo, steroids, hyaluronic and PRP for knee osteoarthritis: a Bayesian network meta-analysis. Arch Orthop Trauma Surg. 2020 Jul 28. doi: 10.1007/s00402-020-03551-y. Epub ahead of print. PMID: 32725315. 
 
Wu YT, Hsu KC, Li TY, Chang CK, Chen LC. Effects of Platelet-Rich Plasma on Pain and Muscle Strength in Patients With Knee Osteoarthritis. Am J Phys Med Rehabil. 2018;97(4):248-54. doi: 10.1097/PHM.0000000000000874. PMID : 29210705 
 
Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH. Intra-articular Injection of Platelet-Rich Plasma Is Superior to Hyaluronic Acid or Saline Solution in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized, Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial. Arthroscopy. 2019;35(1):106-17. doi: 10.1016/j.arthro.2018.06.035. PMID : 30611335 

Bruno BOEZENNEC, MD, Managing Editor