Questions about biologic care that starts with blood or body tissue

Sources

1. A cross-sectional study contacted 273 of 317 US centres offering direct-to-consumer stem-cell therapy, posing as a 57-year-old man with knee osteoarthritis. The mean advertised price of a unilateral same-day stem-cell knee injection was $5,156 (SD $2,446; 95% CI $4,550-5,762, n=65) and the mean claimed clinical efficacy was 82% (SD 9.6%; n=36) - a figure the authors describe as a gap between marketing claims and the published literature.

   Piuzzi NS, et al. — The Stem-Cell Market for the Treatment of Knee Osteoarthritis: A Patient Perspective.. Journal of Knee Surgery, 2018. DOI: 10.1055/s-0037-1604443.

2. Medicare's national coverage determination states that CMS covers autologous platelet-rich plasma ONLY for patients with chronic non-healing diabetic, pressure and/or venous wounds, and only inside an approved coverage-with-evidence-development clinical study. Every approved study listed under the NCD is a wound-healing study. There is no Medicare national coverage for PRP in osteoarthritis or tendinopathy, which is why these injections are billed to the patient.

   Centers for Medicare & Medicaid Services — Autologous Platelet-rich Plasma (Coverage with Evidence Development). CMS.gov, 2024.

3. The largest head-to-head trial of cell-based orthobiologics to date randomised 480 patients with KL II-IV knee OA across four arms: autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction, allogeneic umbilical cord tissue-derived MSCs, and a corticosteroid injection control. At 12 months NONE of the three orthobiologic injections was superior to another or to the corticosteroid control on either co-primary endpoint (VAS pain, KOOS pain), and none of the four groups showed a significant change in MRI osteoarthritis score from baseline. No procedure-related serious adverse events were reported.

   Mautner K, et al. — Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.. Nature Medicine, 2023. DOI: 10.1038/s41591-023-02632-w.

4. RESTORE, the largest and most rigorously blinded placebo-controlled PRP trial in knee OA (n=288, participant-, injector- and assessor-blinded), gave three weekly injections of a commercial leukocyte-poor PRP or saline. At 12 months the change in knee pain was -2.1 vs -1.8 points (difference -0.4; 95% CI -0.9 to 0.2; P=.17) and the change in medial tibial cartilage volume was -1.4% vs -1.2% (difference -0.2%; P=.81). Twenty-nine of 31 prespecified secondary outcomes showed no between-group difference. The authors concluded the findings do not support the use of PRP for knee OA.

   Bennell KL, et al. — Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial.. JAMA, 2021. DOI: 10.1001/jama.2021.19415.

5. FDA states verbatim of stem cell products, stromal vascular fraction (adipose-derived cells), umbilical cord blood, Wharton's jelly, amniotic fluid and exosome products: 'None of these products have been approved for the treatment of any orthopedic condition, such as osteoarthritis, tendonitis, disc disease, tennis elbow, back pain, hip pain, knee pain, neck pain, or shoulder pain.' The only FDA-approved stem cell products in the United States are blood-forming (hematopoietic progenitor) cells derived from umbilical cord blood, approved only for disorders of blood production, and there are currently NO FDA-approved exosome products.

   U.S. Food and Drug Administration — Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. FDA (Center for Biologics Evaluation and Research), 2020.