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

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 Patients reporting unacceptable pain at 3 months were considered treatment failures and withdrawn from the study.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.

A novel placental tissue biologic, PTP-001, inhibits inflammatory and catabolic responses in vitro and prevents pain and cartilage degeneration in a rat model of osteoarthritis

“…That subsequent study (ClinicalTrials.gov Identifier: NCT02318511) comprised 200 OA patients randomized to receive a single injection of ASA, hyaluronic acid, or saline. Subjects who received ASA injections demonstrated superior efficacy in measures of pain and function at 3 and 6 months post-treatment 43 . In a separate study, a noted reduction in pain at 6 months post-injection was reported for 20 OA patients that were treated with an IA injection of morselized amniotic membrane/umbilical cord tissue 44 .…”

A Single Injection of Amniotic Suspension Allograft Is Safe and Effective for Treatment of Mild to Moderate Hip Osteoarthritis: A Prospective Study

“…At 6 months posttreatment, the ASA group had significantly greater improvement from baseline in J o u r n a l P r e -p r o o f multiple PRO subsets as compared to the HA and saline groups, with a significantly greater responder rate (69.1%) in the ASA group. They concluded that ASA injections produce a clinically meaningful improvement in symptoms of knee OA as compared to HA and saline injections 12 .…”

“…Amniotic tissue was initially described for clinical use as a biologic dressing for skin defects 9 . Uses of amniotic membrane tissue have evolved to include treatment for ophthalmologic conditions, complex wounds, and more recently for orthopedic conditions such as tendinopathy and osteoarthritis [10][11][12] .…”

“…Corticosteroid, platelet rich plasma and hyaluronic acid intra-articular injections have been used to treat symptomatic hip osteoarthritis with limited success [19][20][21][22][23] . Amniotic membrane and fluid-derived products represent a promising treatment option for patients with OA 11,12 , particularly those with moderate disease who are less likely to benefit from hip arthroscopy, yet are not indicated for arthroplasty due to age or severity of disease.…”

Safety and efficacy of umbilical cord-derived Wharton’s jelly compared to hyaluronic acid and saline for knee osteoarthritis: study protocol for a randomized, controlled, single-blind, multi-center trial

“…By 2030, the number of US adults with arthritis is expected to reach 67 million, leading to a continuous increase in the number of total knee replacement surgeries [ 2 – 4 ]. While total knee replacement surgeries have shown advantages, avoiding or delaying such surgery is usually desirable, for medical reasons and health care system perspective [ 5 ]. The long-term outcomes after total knee replacement surgeries for patients with grade II or III knee OA on the Kellgren-Lawrence (KL) scale are worse compared to patients with grade IV OA [ 6 , 7 ].…”