Preventative and Disease-Modifying Investigations for Osteoarthritis Management Are Significantly Under-represented in the Clinical Trial Pipeline: A 2020 Review

DePhillipo, Nicholas N.; Aman, Zachary S.; Dekker, Travis J.; Moatshe, Gilbert; Chahla, Jorge; LaPrade, Robert F.

doi:10.1016/j.arthro.2021.03.050

Cited by 7 publications

(7 citation statements)

References 54 publications

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“…This is what DePhillipo, Aman, Dekker, Moatshe, Chahla, and LaPrade have accomplished. 15 In their study titled "Preventative and Disease-Modifying Investigations for Osteoarthritis Management Are Significantly Underrepresented in the Clinical Trial Pipeline: A 2020 Review," DePhillipo et al…”

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confidence: 99%

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Editorial Commentary: More Clinical Trials Should Focus on Primary Prevention of Osteoarthritis: Disruptive Thinkers Are Required

Hohmann¹

2021

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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With increasing life expectancy and an increased prevalence of osteoarthritis, the total number of individuals with symptomatic degenerative arthritis will most likely increase considerably. The current focus of nonoperative treatment is on weight loss, exercise, muscle strengthening, physical therapy, nonsteroidal anti-inflammatory drugs, intraarticular injection therapies with corticosteroids, hyaluronic acid, or platelet-rich plasma, and lately, disease-modifying drugs. Obviously, prevention is better than cure, but only 5% of all studies registered on ClinicalTrials.gov in the United States are intending to develop strategies for prevention. The overall majority of included studies (89%) will target symptom resolution, and 6% will investigate disease-modifying drugs.

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Section: See Related Article On Page 2627mentioning

confidence: 99%

“…We definitely need outside-the-box thinkers to help us out here. DePhillipo et al 15 have set the stage and provided us with an inventory, and now it is time to get to work.…”

Section: See Related Article On Page 2627mentioning

confidence: 99%

Editorial Commentary: More Clinical Trials Should Focus on Primary Prevention of Osteoarthritis: Disruptive Thinkers Are Required

Hohmann¹

2021

Arthroscopy: The Journal of Arthroscopic & Related Surgery

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“…Various growth factors (e.g., fibroblast growth factor 18 [FGF-18], bone morphogenic protein, transforming growth factor β) have been suggested for use as augmentative therapies for enhancing cartilage and bone regeneration in orthopedic procedures. 5 - 10 One of the growth factors with well-known anabolic effects on cartilage is FGF-18, which is a member of the fibroblast growth factor family and has shown to play a central role in skeletogenesis. Prior studies have demonstrated the capacity of FGF-18 to increase collagen type II and reduce collagen type II breakdown following cartilage injury.…”

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confidence: 99%

Preclinical Use of FGF-18 Augmentation for Improving Cartilage Healing Following Surgical Repair: A Systematic Review

et al. 2022

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Objective To evaluate the efficacy of fibroblast growth factor-18 (FGF-18) augmentation for improving articular cartilage healing following surgical repair in preclinical ( in vivo) animal models. Design A systematic review was performed evaluating the efficacy of FGF-18 augmentation with cartilage surgery compared with cartilage surgery without FGF-18 augmentation in living animal models. Eligible intervention groups were FGF-18 treatment in conjunction with orthopedic procedures, including microfracture, osteochondral auto/allograft transplantation, and cellular-based repair. Outcome variables were: International Cartilage Repair Society (ICRS) score, modified O’Driscoll histology score, tissue infill score, qualitative histology, and adverse events. Descriptive statistics were recorded and summarized for each included study. Results In total, 493 studies were identified and 4 studies were included in the final analysis. All studies were randomized controlled trials evaluating in vivo use of recombinant human FGF-18 (rhFGF-18). Animal models included ovine ( n = 3) and equine ( n = 1), with rhFGF-18 use following microfracture ( n = 3) or osteochondral defect repair ( n = 1). The rhFGF-18 was delivered via intra-articular injection ( n = 2), collagen membrane scaffold ( n = 1), or both ( n = 1). All studies reported significant, positive improvements in cartilage defect repair with rhFGF-18 compared with controls based on ICRS score ( n = 4), modified O’Driscoll score ( n = 4), tissue infill ( n = 3), and expression of collagen type II ( n = 4) ( P < 0.05). No adverse events were reported with the intra-articular administration of this growth factor, indicating short-term safety and efficacy of rhFGF-18 in vivo. Conclusion This systematic review provides evidence that rhFGF-18 significantly improves cartilage healing at 6 months postoperatively following microfracture or osteochondral defect repair in preclinical randomized controlled trials.

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“…At present, available painkillers are not safe enough as long-term treatments. Therefore, recommendations for the management of OA are based on nonpharmacologic strategies, such as activity modifications, exercise programs, and weight control 11. With the advent of regenerative medicine, intra-articular injections of several biological products have been proposed aiming to reduce pain and restore joint homeostasis 12.…”

mentioning

confidence: 99%

“…Therefore, recommendations for the management of OA are based on nonpharmacologic strategies, such as activity modifications, exercise programs, and weight control. 11 With the advent of regenerative medicine, intra-articular injections of several biological products have been proposed aiming to reduce pain and restore joint homeostasis. 12 Biological therapies are multimolecular, and may simultaneously target various signaling pathways, including nociceptive and neuropathic pain signaling.…”

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confidence: 99%

Biological Targets of Multimolecular Therapies in Middle-Age Osteoarthritis

Andı́a

Atilano

Maffulli

2022

Sports Medicine and Arthroscopy Review

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Knee osteoarthritis (OA) is a common condition, prevalent in middle-agedness, associated with chronic pain and impaired quality of life. Two interrelated biological processes fuel early OA progression: inflammation and structural tissues catabolism. Procatabolic and proinflammatory mediators are interconnected and form part of a self-perpetuating loop. They leverage OA research complexity because of the impossibility to discern certain spatiotemporal tissues’ changes from others. Both are shared targets of versatile regenerative multimolecular therapies. In particular, platelet-rich plasma can interfere with inflammation and inflammatory pain. The therapeutic approach is to alter the vicious inflammatory loop by modifying the molecular composition of the synovial fluid, thereby paracrine cellular cross talk. Intra-articular injections of platelet-rich plasma can provide key factors balancing proinflammatory and anti-inflammatory factors, targeting macrophage dysfunction and modulating immune mechanisms within the knee.

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Preventative and Disease-Modifying Investigations for Osteoarthritis Management Are Significantly Under-represented in the Clinical Trial Pipeline: A 2020 Review

Cited by 7 publications

References 54 publications

Editorial Commentary: More Clinical Trials Should Focus on Primary Prevention of Osteoarthritis: Disruptive Thinkers Are Required

Editorial Commentary: More Clinical Trials Should Focus on Primary Prevention of Osteoarthritis: Disruptive Thinkers Are Required

Preclinical Use of FGF-18 Augmentation for Improving Cartilage Healing Following Surgical Repair: A Systematic Review

Biological Targets of Multimolecular Therapies in Middle-Age Osteoarthritis

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