A Single-Blinded Randomized Controlled Trial of Mesenchymal Stem Cell Therapy for the Treatment of Osteoarthritis of the Knee with Active Control.

Background: Osteoarthritis is most prevalent in the knee and drives the growing incidence of total knee arthroplasty. There is a need to explore non-surgical treatment options to increase the portfolio of alternatives available. The study aimed to determine the clinical response to an autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) intra-articular injection compared to an active comparator. Methods: The study was a prospective, single-blinded, randomized controlled pilot study. Participants with diagnosed knee osteoarthritis were allocated to one of two treatment groups to receive a BMAC injection immediately followed by a PRP injection or a single injection of Gel-One® crosslinked hyaluronate (HA). Outcomes were assessed at 3, 6, and 12 months post-treatment. Results: Significant improvements were observed in both treatment groups for all Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales with the exception of the symptoms assessment at 12 months in the HA group. BMAC KOOS scores peaked at 12 months, while HA KOOS scores generally peaked at 6 months. The gap in mean scores at 12 months in favor of the BMAC group did not reach statistical significance. Secondary outcomes included a greater reduction in pain at 12 months in the BMAC group (-3.13 points; 95% CI: -3.96, -3.29) compared to the HA group (-1.56 points; 95% CI: -2.59, -0.53; p= 0.02) via the numeric pain rating scale. Conclusions: Results demonstrate that both treatment groups experienced clinically and statistically significant improvement across the KOOS subscales. While BMAC has shown promise in the treatment of knee OA, there is a need for multi-center investigations with larger sample sizes, an extended follow-up, and placebo-based control. ClinicalTrials.gov Identifier: NCT02958267.

Outcomes of a conservative care program for knee osteoarthritis through translation of research into practice.

INTRODUCTION: Evidence-based guidelines suggest a conservative, nonsurgical approach as first-line treatment for knee osteoarthritis. However, previous literature has documented underutilization of the fundamental components of condition management emphasized in the guidelines. The intervention aim is to apply organized conservative components of care for knee osteoarthritis in an evidence-based management program through the translation of research into practice with a target to observe meaningful functional improvement in a distinct population. METHODS: The program, modeled after the nonsurgical arm of a randomized, controlled trial, was designed as a single-arm observational cohort study with a pre- and post-program comparison for participants reporting presence of knee osteoarthritis who were attributed to a specific employer's health plan in the United States. The 12-week intervention consisted of condition education, group exercise, and a dietary intervention. RESULTS: Ninety-six participants enrolled in the program, of which 72% completed the protocol. The median change in pre- to post-program Knee Injury and Osteoarthritis Outcome Score values was 10.4 ± 0.8 (Z = 210.5, p < 0.001)-a clinically important change. Secondary outcomes were complementary to the primary outcome. CONCLUSIONS: Results of the program indicate that the clinically significant 3-month findings in the report by Skou et al. (2015) regarding functional improvement can be replicated in an alternate setting. Organizing and offering fundamental components of condition management in a group format with provider oversight could be a feasible and logical component in the continuum of care for knee osteoarthritis, while complementing other secondary management strategies following diagnosis.

Efficacy of Triamcinolone Acetonide Extended-Release in Participants with Unilateral Knee Osteoarthritis: A Post Hoc Analysis.

INTRODUCTION: Osteoarthritis (OA) is common and its prevalence is increased in military service members. In a phase 3 randomized controlled trial (NCT02357459), a single intra-articular injection of an extended-release formulation of triamcinolone acetonide (TA-ER) in participants with unilateral or bilateral knee OA demonstrated substantial improvement in pain and symptoms. Bilateral knee pain has emerged as a confounding factor in clinical trials when evaluating the effect of a single intra-articular injection. Furthermore, unilateral disease is frequently first to emerge in active military personnel secondary to prior traumatic joint injury. In this post hoc analysis, we assessed efficacy and safety of TA-ER in a subgroup of participants with unilateral knee OA. METHODS: Participants ≥ 40 years of age with symptomatic knee OA were randomized to a single intra-articular injection of TA-ER 32 mg, TA crystalline suspension (TAcs) 40 mg, or saline-placebo. Average daily pain (ADP)-intensity and rescue medication use were collected at each of weeks 1-24 postinjection; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-A (pain), WOMAC-B (stiffness), WOMAC-C (function), and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QoL) were collected at weeks 4, 8, 12, 16, 20, and 24 postinjection. Adverse events (AEs) were assessed throughout the study. Participants with unilateral knee OA were selected for this analysis. RESULTS: Of 170 participants with unilateral OA (TA-ER, N = 51; saline-placebo, N = 60; TAcs, N = 59), 42% were male and 89% were white. TA-ER significantly (p < 0.05) improved ADP-intensity vs. saline-placebo (weeks 1-24) and TAcs (weeks 4-21). TA-ER significantly (p < 0.05) improved WOMAC-A vs. saline-placebo (all time points) and TAcs (weeks 4, 8, 12, 24). Consistent outcomes were observed for rescue medication, WOMAC-B, WOMAC-C, and KOOS-QoL. AEs were similar in frequency/type across treatments. CONCLUSION: TA-ER provided 5-6 months' pain relief that consistently exceeded saline-placebo and TAcs, suggesting that TA-ER injected intra-articularly into the affected knee may be an effective non-opioid treatment option. Although the participants included in this analysis did not fully represent the diverse demographics of active service members, the substantial unmet medical need in the military population suggests that TA-ER may be an important treatment option; additional studies of TA-ER in active military patients are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02357459. FUNDING: Flexion Therapeutics, Inc. Plain language summary available for this article.

Viscosupplementation for Osteoarthritis of the Knee: A Key Opinion Leader Panel Discussion.

With a sharp rise in the prevalence of osteoarthritis of the knee (OAK) in a younger population, new management strategies are needed to preserve mobility, improve patients' quality of life, and reduce the effects of potential disease-related comorbidities. Viscosupplementation with the use of hyaluronic acid (HA) injection is a treatment option for OAK that can provide lubrication and elastic shock absorption, leading to potential pain relief, improved function, and reduced stiffness. A key opinion leader (KOL) panel discussion was held December 3, 2016, with the objective of sharing opinions, ideas, information, and trends regarding OAK and the potential treatment and management offered by viscosupplementation. The panel concluded that viscosupplementation with HA injections presents a viable, cost-effective, and safe alternative for the treatment of OAK. DISCLOSURES: This panel discussion and report was facilitated by Magellan Rx Manage-ment and funded by Sanofi. Bert and Ruane report fees from Sanofi outside of this project. Sgaglione reports royalty payments from Zimmer Biomet and Wolters Kluwer. Dasa has received fees from Bioventus and Myoscience. All the authors received an honorarium for work on this project. Lopes is employed by Magellan Rx Management.

Randomized trial assessing the impact of a musculoskeletal intervention for pain before participating in a weight management program.

PURPOSE: Obesity increases the risk of developing physical disability and pain. Persons with a body mass index (BMI) of 30 kg/m or more have an increased risk for osteoarthritis compared with those with a BMI between 25 and 29 kg/m. The purpose of this study was to examine the effect of treatment directed at reducing musculoskeletal pain on weight loss in obese subjects prior to participation in a 6-month weight management (WM) program. METHODS: Subjects (BMI > or = 30 kg/m; n = 54, female = 41, male = 13) with musculoskeletal pain, as assessed by a visual analog scale score of more than 5, were randomized to a physician musculoskeletal evaluation with treatment and physical therapy prior to participation in a 6-month WM program (intervention) or direct entry into the WM program (control) between November 10, 2003, and January 20, 2005. RESULTS: Seventy-six percent of subjects completed the study (intervention, n = 18 [67%]; control, n = 23 [85%], P = .10). The intervention group demonstrated a significant decrease in visual analog scale score after musculoskeletal therapy (2.3 +/- 1.8, P < .0001). Despite a reduction in pain levels in the intervention group compared with the control group at the start of the WM program, there were no significant differences between the groups in percentage weight loss (P = .80), body fat composition (P = .20), or BMI (P = .06), all significantly improved in both groups. CONCLUSIONS: Musculoskeletal and physical therapy intervention directed at decreasing musculoskeletal pain in obese individuals prior to participation in a WM program reduces reported musculoskeletal pain for those participants completing the program but does not significantly improve weight loss over 6 months, compared with individuals with comparable musculoskeletal pain who enter directly into a WM program.