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Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis.

ABSTRACT: Intra-articular injections of platelet-rich plasma (PRP) and other novel blood-derived products developed specifically for osteoarthritis (OA) can provide pain relief and potential benefits in disease progression. Meta-analyses show the clinical superiority of PRP compared with other intra-articular injections, but results are modest and the effect sizes are small. PRP injections in knee OA are performed indiscriminately, but the clinical response varies enormously between patients because of an array of mixed OA phenotypes. Subgroup analyses are scarce; some studies stratify patients according to radiographic severity and found better results in early OA, without consensus for more advanced stages of the condition. Parallel identification of soluble and imaging biomarkers is essential to personalise and leverage PRP therapies. The inflammatory phenotype is most interesting from the PRP perspective because PRPs modulate inflammation by releasing a large pool of chemokines and cytokines, which interact with synovial fibroblasts and macrophages; in addition, they can modulate the innate immune response. No soluble biomarkers have been discovered that have implications for OA research and PRP interventions. Clinical examination of patients based on their inflammatory phenotype and imaging identification of pain sources and structural alterations could help discern who will respond to PRP. Synovial inflammation and bone marrow lesions are sources of pain, and intra-articular injections of PRP combined with subchondral bone injection can enhance clinical outcomes. Further refining ultrasound phenotypes may aid in personalising PRP therapies. Intra-articular delivery combined with injections in altered ligamentous structures, medial and coronal ligaments or premeniscal pes anserinus showed positive clinical outcomes. Although the evidence supporting these approaches are weak, they merit further consideration to refine PRP protocols and target the right OA phenotypes.

SUBMITTER: Andia I

PROVIDER: S-EPMC8010808 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Intraarticular hyaluronan or platelet-rich plasma (PRP) is widely used in the treatment of knee osteoarthritis (OA). The efficacy of combined hyaluronan with PRP remained inconclusive. This study aimed to investigate the efficacy of combined a single crosslinked hyaluronan (HYAJOINT Plus) and a single PRP versus a single PRP in patients with knee OA. In a prospective randomized-controlled trial, 85 patients with knee OA (Kellgren-Lawrence 2) were randomized to receive a single intraarticular injection of HYAJOINT Plus (3 ml, 20 mg/ml) followed by 3 ml PRP (the combined-injection group, N = 43) or a single injection of 3 ml PRP (the one-injection group, N = 42). The primary outcome was the change from baseline in the visual analog scale (VAS) pain (0-00 mm) at 6 months. Secondary outcomes included The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, Likert Scale), Lequesne index, single leg stance test (SLS), use of rescue analgesics and patient satisfaction at 1, 3 and 6 months. Seventy-eight patients were available for the intention-to-treat analysis at 6 months. Both groups improved significantly in VAS pain, WOMAC, Lequesne index and SLS at each follow-up visit (p < 0.001). Patients receiving a single PRP experienced significantly greater improvements in VAS pain than patients receiving combined injections at 1-month follow-up (adjusted mean difference: - 5.6; p = 0.017). There were no significant between-group differences in several of the second outcomes at each follow-up visit, except the WOMAC-pain and WOMAC-stiffness scores favoring the one-injection group at 1 month (p = 0.025 and p = 0.011). However, at 6-month follow-up, the combined-injection group achieved significantly better VAS pain reduction (p = 0.020). No serious adverse events occurred following injections. In conclusion, either combined injections of HYAJOINT Plus and PRP or a single PRP alone was safe and effective for 6 months in patients with Kellgren-Lawrence 2 knee OA. Combined injections of HYAJOINT Plus and PRP achieved better VAS pain reduction than a single PRP at 6 months. The results indicating a long term benefit effect of a combination of HYAJOINT Plus and PRP in a particular subset of patients with moderate knee OA need to be replicated in larger trials.ClinicalTrials.gov number NCT04315103.

Project description:IntroductionKnee osteoarthritis (KOA) is a progressive joint disease commonly treated with intra-articular injections, including platelet-rich plasma (PRP), hyaluronic acid (HA), or corticosteroids (CS). This updated meta-analysis aims to enhance the statistical power of the results and provide comprehensive clinical evidence that reflects the most current research. By doing so, the authors aim to suggest a reliable estimate for the development of guidelines, addressing the pressing need for effective and minimally invasive treatment options.MethodsPubMed, Scopus, clinicaltrials.gov, Cochrane Central were searched until March 2023, for randomized controlled trials (RCTs) comparing the effectiveness of intra-articular injectable therapies, including PRP, HA, CS, and placebo, in KOA. Data extraction involved baseline characteristics and outcome measures [Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Visual Analog Scale (VAS) pain scores, KOOS, and IKDC scores] at 1, 3, 6 and 12 months. Statistical analysis, including subgroup analysis, assessment of heterogeneity, and publication bias, was conducted using Review Manager.ResultsOur meta-analysis of 42 studies involving 3696 patients demonstrated that PRP treatment resulted in significant pain relief compared to HA injections, as evidenced by improved WOMAC pain (MD: -0.74; 95% CI: -1.02 to -0.46; P≤0.00001; I 2=94%) and VAS pain (MD: -0.65; 95% CI: -1.24 to -0.06; P=0.03; I2=97%) outcomes. Similarly, PRP showed greater efficacy in reducing WOMAC pain (MD: -8.06; 95% CI: -13.62 to -2.51: P=0.004; I 2=96%) and VAS pain (MD: -1.11; 95% CI: -1.64 to -0.59; P≤0.0001; I 2=68%) compared to CS injections, with the most significant improvement observed at 6 months.ConclusionsPRP is an effective treatment for KOA. It provides symptomatic relief, has the potential to reduce disease progression, and has sustained effects up to 12 months. PRP offers superior pain relief and functional enhancement compared to CS and HA injections.

Project description:BackgroundKnee osteoarthritis (OA) is a common, chronic, progressive and degenerative disease which affects patients' quality of life and may cause disability and social isolation. OA is a huge economic burden for the patient and a large strain for the whole healthcare system. Articular cartilage has a small potential to repair, with progressively more clinicians emphasizing cellular therapy. Subcutaneous fat tissue in human body is a large reservoir of mesenchymal stem cells (MSCs) and is been harvested in minimally invasive, simple procedure. Up to date there is no prospective randomized controlled studies demonstrating effectiveness and role of adipose tissue injections in OA treatment. The purpose of this study is to assess functional and clinical changes among patients with symptomatic knee OA treated with intra-articular injections of autologous adipose tissue or platelet rich plasma (PRP) and to compare efficacy of both therapeutic methods.MethodsThis is a prospective, randomized, controlled study. Patients who meet inclusion criteria will be allocated to Fat Tissue group or PRP group randomly. Subjects will receive an intra articular injection with autologous adipose tissue and PRP respectively. Patients will be assessed five times: before treatment and 1, 3, 6 and 12 months after the treatment. The assessment consists of patient reported outcome measures (The Knee injury and Osteoarthritis Outcome Score, International Knee Documentation Committee 2000, the Western Ontario and McMaster Universities Osteoarthritis Index, the Health Questionnaire EQ- 5D- 5 L), three functional tests (The Timed Up and Go Test, The 5 Times Sit to Stand Test, The 10 m Walk Test) and Maximal Isometric Voluntary Contraction.DiscussionThis study protocol has several strengths and weaknesses. One of strongest point of this study is the wide, multidimensional functional assessment which will give a large amount of objective data. On the other hand, lack of blinding has to be considered as a risk of both subject and investigator bias.Trial registrationname of registry: ClinicalTrials.gov, trial registration number: NCT04321629, retrospectively registered on date of registration.

Project description:BackgroundIntraarticular plasma-rich platelet (PRP) and hyaluronic acid (HA) have each been shown to be effective for treating knee osteoarthritis (OA). Evidence supporting the combination therapy is controversial. This study aimed to investigate the efficacy of a single intraarticular PRP injection combined with different HAs in patients with knee OA.MethodsIn this prospective randomized-controlled trial, 99 patients with Kellgren-Lawrence grade 2 knee OA with average knee pain ≥ 30 mm on a 0-100 mm pain visual analog scale (VAS) were randomized into two groups. The PRP + Artz group received a single intraarticular HA (Artz, 2.5 ml, 10 mg/ml) followed by 3 ml PRP (n = 50). The PRP + HYAJOINT Plus group received a single intraarticular cross-linked HA (HYAJOINT Plus, 3 ml, 20 mg/ml) followed by 3 ml PRP (n = 49). All patients were evaluated before and at 1, 3 and 6 months after injections. The primary outcome was the VAS pain reduction from baseline at 6 months. Secondary outcome measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne index, single leg stance (SLS) test and patient satisfaction.ResultsNinety-five patients were analyzed by intention-to-treat analysis. Both groups improved significantly in VAS pain, WOMAC, Lequesne index and SLS at 1, 3 and 6 months post intervention (p < 0.05). Between-group comparisons showed no significant differences at most follow-up time points, except better improvements in Lequesne index at 1 month (p = 0.003) and WOMAC-stiffness score at 6 months (p = 0.020) in the PRP + Artz group, and superiority in SLS at 1, 3 and 6 months in the PRP+ HYAJOINT Plus group (p < 0.001, p = 0.003 and p = 0.004). Additional Johnson-Neyman analyses showed that among the patients with baseline WOMAC-pain score > 8.5, WOMAC-function score > 21.7 and WOMAC-total score > 32.0, respectively, those treated with PRP + HYAJOINT Plus injections had better effects in WOMAC-pain, WOMAC-function and WOMAC-total scores than those treated with PRP + Artz at 3 months postinjection (p < 0.05). Both groups reported high satisfaction. No serious adverse events occurred during the study.ConclusionsA single PRP injection combined with Artz or HYAJOINT Plus is effective and safe for 6 months in patients with knee OA. Both injection regimens are potential treatment options for knee OA. Further studies are needed to confirm these results.Trial registrationThe study was registered at ClinicalTrials.gov (NCT04931719), retrospectively. Date of registration 18/6/2021.Name of trial registryComparing efficacy of single PRP combined with different hyaluronans for knee osteoarthritis.Level of evidenceTherapeutic Level 1.

Project description:BackgroundStudies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA.MethodsThe PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation.ResultsSeven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: - 0.31; 95% confidence interval (CI): - 0.55 to - 0.06; P = 0.01 < 0.05). PRP combined with HA for KOA achieved better improvements in the WOMAC Function Score (SMD: -0.32; 95% CI: - 0.54 to - 0.10; P < 0.05) and WOMAC Total Score (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05) at the 12-month follow-up than did the application of PRP alone. In a comparison of Lequesne Index scores at the 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: - 0.67 to - 0.17; P < 0.05). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone (P > 0.05).ConclusionsCompared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.

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Moving toward targeting the right phenotype with the right platelet-rich plasma (PRP) formulation for knee osteoarthritis.

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