Medical Research
Common treatment for joint pain may be linked to faster arthritis progression, research suggests
Two new unpublished studies suggest that patients who got corticosteroid shots saw their knee arthritis advance more quickly than those who didn’t. Click here to read more.
An Initial Injection and a Crossover Injection of Amniotic Suspension Allograft Following Failed Treatment with Hyaluronic Acid or Saline Are Equally Effective in the Treatment of Moderate Symptomatic Knee Osteoarthritis Over 12 Months
Andreas H Gomoll, Bert R Mandelbaum, Jack Farr, W Tad Archambault, Seth L Sherman, Samuel K Tabet, Kelly A Kimmerling, Katie C Mowry
Arthroscopy
Volume 39, Issue 1, January 2023, Pages 66-78
DOI: 10.1016/j.arthro.2022.06.036
Abstract
Purpose: The purpose of this crossover study was to determine the efficacy of amniotic suspension allograft (ASA) for moderate symptomatic knee osteoarthritis following failed treatment with hyaluronic acid (HA) or saline through 12 months' postcrossover injection using patient-reported and safety outcomes.
Methods: In this multicenter study, 95 patients from a 200-patient single-blind randomized controlled trial were eligible to crossover and receive a single injection of ASA 3 months after failed treatment with HA or saline. Patient-reported outcomes, including Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS), were collected out to 12 months postcrossover to determine pain and function. Radiographs and blood were collected for assessment of changes. Statistical analyses were performed using mixed effects model for repeated measures.
Results: Treatment with ASA following failed treatment with HA or saline resulted in significant improvements in KOOS and VAS scores compared with crossover baseline. There were no differences in radiographic measures or anti-human leukocyte antigen serum levels compared with baseline and no severe adverse events reported. In addition, more than 55% of patients were responders at months 3, 6, and 12 as measured by the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International simplified responder criteria. There were no significant differences between the original ASA randomized group and crossover cohorts at any of the time points evaluated, suggesting that prior failed treatment with HA or saline did not significantly impact outcomes following treatment with ASA.
Conclusions: This study showed that patients who previously failed treatment with HA or saline had statistically significant improvements in pain and function scores following a crossover injection of ASA that was sustained for 12 months, as measured by KOOS and VAS. There were no serious adverse events reported, and the injection was safe.
Level of evidence: II, prospective cohort study.
Safety and Efficacy of an Amniotic Suspension Allograft Injection Over 12 Months in a Single-Blinded, Randomized Controlled Trial for Symptomatic Osteoarthritis of the Knee
Andreas H Gomoll, Jack Farr, Brian J Cole, David C Flanigan, Christian Lattermann, Bert R Mandelbaum, Sabrina M Strickland, Kenneth R Zaslav, Kelly A Kimmerling, Katie C Mowry
Arthroscopy
Volume 37, Issue 7, July 2021, Pages 2246-2257
DOI: 10.1016/j.arthro.2021.02.044
Abstract
Purpose: The purpose of this study is to determine the efficacy of amniotic suspension allograft (ASA) compared to hyaluronic acid (HA) and saline at up to 12 months of follow-up through the use of patient-reported outcomes, immunoglobulin levels, and anti-human leukocyte antigen (HLA) levels.
Methods: Within this multicenter study, 200 patients were randomized 1:1:1 to a single intra-articular injection of saline, HA, or ASA. Patient-reported outcomes, including Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS) score, were collected at multiple time points (baseline, 1 week, 6 weeks, 3 months, 6 months) out to 12 months to assess improvements in pain and function. Radiographs at baseline and 12 months were taken to determine radiographic changes, while blood was collected at baseline, 6 weeks, and 6 months to determine changes in immunoglobulins and anti-HLA levels. Statistical analyses were performed using last observation carried forward and mixed effects model for repeated measures.
Results: Treatment with ASA resulted in significant improvements in KOOS and VAS scores that were maintained through 12 months (P < .05). Treatment with ASA resulted in a 63.2% responder rate at 12 months using the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International simplified definition. There were no significant differences between groups for radiographic measures in the index knee, immunoglobulins, C-reactive protein, or anti-HLA serum levels (P > .05). The number and type of adverse events (AEs) reported for ASA were comparable to the HA injection group, while no treatment-emergent AEs were reported for the saline group.
Conclusions: This randomized controlled trial of ASA vs HA and saline for the treatment of symptomatic knee osteoarthritis demonstrated clinically meaningful improved outcomes with ASA over the controls out to 12 months postinjection. No concerning immunologic or adverse reactions to the ASA injection were identified with regards to severe AEs, immunoglobulin, or anti-HLA levels.
Level of evidence: Level I, randomized controlled multicenter trial.
Amniotic membrane-mesenchymal stromal cells secreted factors and extracellular vesicle-miRNAs: Anti-inflammatory and regenerative features for musculoskeletal tissues
Enrico Ragni, Andrea Papait, Carlotta Perucca Orfei, Antonietta Rosa Silini, Alessandra Colombini, Marco Viganò, Francesca Libonati, Ornella Parolini, Laura Girolamo
Stem Cells Translational Medicine
Volume 10, Issue 7, July 2021, Pages 1044-1062
DOI: 10.1002/sctm.20-0390
Abstract
Human amniotic membrane-derived mesenchymal stromal cells (hAMSCs) are easily obtained in large quantities and free from ethical concerns. Promising therapeutic results for both hAMSCs and their secreted factors (secretome) were described by several in vitro and preclinical studies, often for treatment of orthopedic disorders such as osteoarthritis (OA) and tendinopathy. For clinical translation of the hAMSC secretome as cell-free therapy, a detailed characterization of hAMSC-secreted factors is mandatory. Herein, we tested the presence of 200 secreted factors and 754 miRNAs in extracellular vesicles (EVs). Thirty-seven cytokines/chemokines were identified at varying abundance, some of which involved in both chemotaxis and homeostasis of inflammatory cells and in positive remodeling of extracellular matrix, often damaged in tendinopathy and OA. We also found 336 EV-miRNAs, 51 of which accounted for more than 95% of the genetic message. A focused analysis based on miRNAs related to OA and tendinopathy showed that most abundant EV-miRNAs are teno- and chondro-protective, able to induce M2 macrophage polarization, inhibit inflammatory T cells, and promote Treg. Functional analysis on IL-1β treated tenocytes and chondrocytes resulted in downregulation of inflammation-associated genes. Overall, presence of key regulatory molecules and miRNAs explain the promising therapeutic results of hAMSCs and their secretome for treatment of musculoskeletal conditions and are a groundwork for similar studies in other pathologies. Furthermore, identified molecules will pave the way for future studies aimed at more sharply predicting disease-targeted clinical efficacy, as well as setting up potency and release assays to fingerprint clinical-grade batches of whole secretome or purified components.
A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms
Jack Farr, Andreas H Gomoll, Adam B Yanke, Eric J Strauss, Katie C Mowry; ASA Study Group
The Journal of Knee Surgery
Volume 32, Issue 11, November 2019, Pages 1143-1154
Abstract
Placental-derived tissues are a known source of anti-inflammatory and immune modulating factors. Published pilot data on amniotic suspension allograft (ASA) for the treatment of osteoarthritis (OA) demonstrated safety and trends for improved pain and function. A multicenter randomized controlled trial was designed to evaluate the efficacy of symptom modulation with ASA compared with saline and hyaluronic acid (HA) in subjects with knee OA. A total of 200 subjects were randomized 1:1:1 to ASA, HA, or saline, with subjects blinded to their allocation. Changes from baseline of patient-reported outcomes (PROs)-EQ-5D-5L, Knee Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS), Tegner, and Single Assessment Numerical Evaluation (SANE)-were compared between groups. Patients reporting unacceptable pain at 3 months were considered treatment failures and withdrawn from the study. Statistical analysis was completed by comparing changes in PROs from baseline to 3 and 6 months for all groups. Comparison of demographics between treatment groups showed no significant differences between groups. Patients reporting unacceptable pain at 3 months in each group were ASA (13.2%), HA (68.8%), and saline (75%). Patients receiving ASA demonstrated significantly greater improvements from baseline for overall pain (VAS), KOOS pain, and KOOS-activities of daily living scores compared with those in the HA group (3 months) and both groups (6 months). ASA patients had significantly greater improvements in KOOS symptom scores compared with HA and saline at 3 and 6 months, respectively. OMERACT-OARSI responder rates for ASA, HA, and saline groups were 69.1, 39.1, and 42.6%, respectively (p = 0.0007). Subjects receiving ASA treatment showed greater improvements in PROs and fewer patients reported unacceptable pain compared with HA and saline. The evidence presented in this Level I Randomized Controlled Trial suggests that ASA injection is an effective treatment for the nonoperative management of symptomatic knee OA.
Randomized Controlled Trial of Micronized Dehydrated Human Amnion/Chorion Membrane (dHACM) Injection Compared to Placebo for the Treatment of Plantar Fasciitis
Shawn Cazzell, DPM, Jordan Stewart, DPM, Patrick S. Agnew, DPM, John Senatore, DPM, Jodi Walters, DPM, Douglas Murdoch, DPM, Alex Reyzelman, DPM, and Stuart D. Miller, MD
Foot & Ankle International
Volume 39, Issue 10, October 2018, Pages 1151-1161
Abstract
Background: Failure of conservative management to reduce/eliminate symptoms of plantar fasciitis (PF) may indicate need for advanced treatments. This study reports Level 1 evidence supporting 3-month safety and efficacy of micronized dehydrated human amnion/chorion membrane (dHACM) injection as a treatment for PF.
Methods: A prospective, single-blind, randomized controlled trial was conducted at 14 sites in the United States. Subjects were randomized to receive 1 injection, in the affected area, of micronized dHACM (n=73) or 0.9% sodium chloride placebo (n=72). Safety/efficacy assessments were conducted at 4 weeks, 8 weeks, 3 months, 6 months, and 12 months postinjection, using visual analog scale (VAS) for pain, Foot Function Index–Revised (FFI-R) score, and presence/absence of adverse events. Primary outcome was mean change in VAS score between baseline and 3 months expressed as difference in means for treatment versus control subjects. Secondary outcome was mean change in FFI-R score between baseline and 3 months expressed as difference in means for treatment versus control subjects.
Results: Baseline VAS scores were similar between groups. At the 3-month follow-up, mean VAS scores in the treatment group were 76% lower compared with a 45% reduction for controls (P < .0001), FFI-R scores for treatment subjects had mean reduction of 60% versus baseline, whereas control subjects had mean reduction of 40% versus baseline (P = .0004). Of 4 serious adverse events, none were related to study procedures.
Conclusion: Pain reduction and functional improvement outcomes were statistically significant and clinically relevant, supporting use of micronized dHACM injection as a safe and effective treatment for PF.
Level of Evidence: Level I, prospective randomized trial.