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Clinical Trial
. 2023 Dec;29(12):3120-3126.
doi: 10.1038/s41591-023-02632-w. Epub 2023 Nov 2.

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

Ken Mautner #  1 , Michael Gottschalk #  2 , Scott D Boden  2 , Alison Akard  2 , Won C Bae  3 , Lora Black  4 , Blake Boggess  5 , Paramita Chatterjee  6 , Christine B Chung  3 , Kirk A Easley  7 , Greg Gibson  8 , Josh Hackel  9 , Katie Jensen  4 , Linda Kippner  6 , Chad Kurtenbach  4 , Joanne Kurtzberg  10 , R Amadeus Mason  2 , Benjamin Noonan  11 , Krishnendu Roy  12 , Verle Valentine  4 , Carolyn Yeago  6 , Hicham Drissi  13
Affiliations
Clinical Trial

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

Ken Mautner et al. Nat Med. 2023 Dec.

Erratum in

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.

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Conflict of interest statement

Several of our authors work for Sanford Health. Sanford Health has a financial interest in InGeneron, Inc., the SVF company used in this study. None of the individual physician has a financial conflict or relationship with InGeneron, Inc. K.M. is a consultant for Lipogems, which is a micronized fat company, not used in this current study. P.C., G.G., L.K., J.K., K.R. and C.Y. all receive separate grant/salary support from the Marcus Foundation, who funded this study.

Figures

Fig. 1
Fig. 1. Consort diagram.
Number randomized to each arm of study with dropouts and reason for dropout included.
Fig. 2
Fig. 2. Primary outcome measures over time.
a,b, Results of primary outcome change from baseline for VAS pain (a) and change from baseline for KOOS pain score (b) by treatment group and months since randomization. The time trend lines are the model-based means and 95% CIs. The vertical lines are the 95% CIs. Sample sizes for each treatment group at each time point are reported below each figure.
Fig. 3
Fig. 3. MRI scoring system used. The MRI is graded from 0 to 69, with the higher number representing more severe grades of OA.
Features: BME (bone marrow edema) or Cyst, fat pad alt SI, fat pad signal intensity alteration. Location: Pat, patella; Troch, trochlea; LFC, lateral femoral condyle; LTP, lateral tibial plateau; MFC, medial femoral condyle; MTP, medial tibial plateau; aLM, anterior horn of lateral meniscus; bLM, body of lateral meniscus; pLM, posterior horn of lateral meniscus; aMM, anterior horn of medial meniscus; bMM, body of Medial Meniscus, pMM, posterior horn of medial meniscus; ACL, anterior cruciate ligament; PCL, posterior cruciate ligament; MCL, medial collateral ligament; LCL, lateral collateral ligament. Prefemoral, pre-femoral fat pad; Suprapatellar, suprapatellar fat pad; Hoffa’s, Hoffa’s fat pad. There was a total of 40 separate scores, adding up to the highest possible score of 69, representing the wort possible grade (that is, worst knee health). The MRI is graded from 0 to 69, with the higher number representing more severe grades of OA.
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