Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial

• Type of Material: Article
• Authors: Kenneth Mautner, Emory University; Michael Gottschalk, Emory University; Scott D Boden, Emory University; Alison B. Akard, Emory University; Won C. Bae, University of California, Davis; Lora Black, Sanford Health; Blake Boggess, Duke Sports Medicine; Paramita Chatterjee, Georgia Institute of Technology; Christine B. Chung, University of California, Davis; Kirk Easley, Emory University; Greg Gibson, Georgia Institute of Technology; Josh Hackel, Andrews Institute; Katie Jensen, Sanford Health; Linda Kippner, Georgia Institute of Technology; Chad Kurtenbach, Sanford Health; Joanne Kurtzberg, Duke University; R. Amadeus Mason, Emory University; Benjamin Noonan, Sanford Health; Krishnendu Roy, Vanderbilt University; Verle Valentine, Sanford Health; Carolyn Yeago, Georgia Institute of Technology; Hicham Drissi, Emory University
• Language: English
• Date: 2023-11-02
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © 2023, The Author(s)
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1038/s41591-023-02632-w; https://doi.org/10.1038/s41591-023-02776-9
• Title of Journal or Parent Work: Nature Medicine
• Volume: 29
• Issue: 12
• Start Page: 3120
• End Page: 3126
• Grant/Funding Information: We also wish to acknowledge and gratefully thank the sponsor of this important study, the Marcus Foundation.
• Keywords: Stem-cell research; Mesenchymal stem cells

Abstract

Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing relative efficacy to each other or corticosteroid injections. Here we aimed to identify the safety and efficacy of cell injections from autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic human umbilical cord tissue-derived mesenchymal stromal cells, in comparison to corticosteroid injection (CSI). The study was a phase 2/3, four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients with a diagnosis of knee osteoarthritis (Kellgren–Lawrence II–IV). Participants were randomized to the three different arms with a 3:1 distribution. Arm 1: autologous bone marrow aspirate concentrate (n = 120), CSI (n = 40); arm 2: umbilical cord tissue-derived mesenchymal stromal cells (n = 120), CSI (n = 40); arm 3: stromal vascular fraction (n = 120), CSI (n = 40). The co-primary endpoints were the visual analog scale pain score and Knee injury and Osteoarthritis Outcome Score pain score at 12 months versus baseline. Analyses of our primary endpoints, with 440 patients, revealed that at 1 year post injection, none of the three orthobiologic injections was superior to another, or to the CSI control. In addition, none of the four groups showed a significant change in magnetic resonance imaging osteoarthritis score compared to baseline. No procedure-related serious adverse events were reported during the study period. In summary, this study shows that at 1 year post injection, there was no superior orthobiologic as compared to CSI for knee osteoarthritis. ClinicalTrials.gov Identifier: NCT03818737