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Structural effects of intra-articular TGF-?1 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial.

ABSTRACT: To determine effects of allogeneic human chondrocytes expressing TGF-?1 (TG-C) on structural progression of MRI features of knee osteoarthritis over a 1 year period.This phase II randomized controlled trial of TG-C included patients with moderate to advanced osteoarthritis. Patients were randomized to receive an intraarticular 3:1 mixture of non-transduced allogeneic human chondrocytes and TG-C or placebo. 3 T MRI was acquired for all patients at baseline and follow-up (3, 6 and 12 months). MRIs were assessed using the WORMS system including cartilage damage, bone marrow lesions (BMLs), meniscal damage/extrusion, Hoffa-, effusion-synovitis, and osteophytes. Analyses were performed on a whole knee level, compartmental level, and subregional level. Binary logistic regression with Generalized Estimating Equation was used to compare risks of progression, adjusting for baseline age and gender. Mann?-?Whitney?-?Wilcoxon tests were used to assess differences for continuous variables.Fifty-seven Patients were included in the TG-C group and 29 in the placebo group. At 12 months, knees in the TG-C group showed less progression of cartilage damage compared to placebo on a whole knee level (34.6% vs. 47.9%; adjusted RR 0.7, 95%CI [0.5-1.1], p?=?0.077). Less progression of Hoffa-synovitis and effusion-synovitis was observed in the TG-C group compared to placebo (9.6% vs. 21.1%, adjusted RR 0.5, 95%CI [0.2,1.2], p?=?0.115). No statistically significant differences were seen for BMLs, meniscal damage and osteophytes.Intraarticular treatment with TG-C showed fewer patients in the treated group with progression in structural OA features and other MRI-defined inflammatory markers such as Hoffa-synovitis and effusion-synovitis. However, no differences were observed in regard to progression of BMLs and meniscal damage, or hypertrophic osteophyte formation.NCT01221441 .Registered 13th October, 2010.

SUBMITTER: Guermazi A

PROVIDER: S-EPMC5689208 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Structural effects of intra-articular TGF-β1 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial.

Guermazi A A Kalsi G G Niu J J Crema M D MD Copeland R O RO Orlando A A Noh M J MJ Roemer F W FW

BMC musculoskeletal disorders 20171116 1

<h4>Background</h4>To determine effects of allogeneic human chondrocytes expressing TGF-β1 (TG-C) on structural progression of MRI features of knee osteoarthritis over a 1 year period.<h4>Methods</h4>This phase II randomized controlled trial of TG-C included patients with moderate to advanced osteoarthritis. Patients were randomized to receive an intraarticular 3:1 mixture of non-transduced allogeneic human chondrocytes and TG-C or placebo. 3 T MRI was acquired for all patients at baseline and f ...[more]

PMID: 29145839

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Project description:IntroductionEvidence has demonstrated greater benefit of intra-articular hyaluronic acid (IA-HA) within earlier stages of knee osteoarthritis (OA) rather than waiting for patients to have progressed to later stages of disease progression. High molecular weight (HMW) HA has also been shown to be more effective than low molecular weight (LMW) HA products in mild to moderate knee OA, providing an important distinction to make within the class of IA-HA therapies. The purpose of this study is to evaluate the cost-effectiveness of treating patients with knee OA with HMW HA compared to LMW and conservative treatment, while taking into account disease stage.MethodsDecision analytic models were created for early/moderate, as well as late stage knee OA. Models for late stage knee OA were created by assuming a range of response rates to IA-HA treatments from 10% to 50%. These models included conservative treatment using physical therapy/exercise, braces/orthosis, and medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. The models compared the cost per quality adjusted life year (QALY) gained for these treatments to the use of either LMW or HMW HA. Incremental cost-effectiveness ratios (ICERs) were calculated for each treatment in relation to HMW HA.ResultsWhen evaluating treatment in early to moderate knee OA, HMW HA was dominant over LMW HA and physical therapy/exercise, as it was less expensive and provided greater benefit. HMW HA was cost-effective versus braces/orthosis and NSAID/analgesic medications based on a willingness to pay threshold of $50,000. In the model of 50% response rate to IA-HA for late stage OA, HMW HA remained cost-effective in comparison to physical therapy/exercise and braces/orthosis at a willingness to pay threshold of $50,000; but not NSAID/analgesic medications. In the worst-case scenario of a 10% responder rate to IA-HA, HMW HA was no longer cost-effective in any circumstance.ConclusionIA-HA, particularly HMW formulations, demonstrate cost-effectiveness when compared to conservative treatment options and LMW HA in patients with early/mid stage knee OA. The cost-effectiveness of HMW HA in patients with later stage knee OA was not as apparent, particularly because of the uncertainty in the proportion of patients with late stage OA who have a meaningful improvement after receiving IA-HA. This cost-effectiveness finding supports the use of IA-HA in patients with early and moderate knee OA, as the benefits of IA-HA are apparent within the patient population with mild to moderate knee OA. The findings of this study suggest that there is a potential cost savings benefit as a result of utilizing HMW HA in earlier stages of knee OA as opposed to later stages.FundingFerring Pharmaceuticals Inc.

Project description:BACKGROUND:The infiltration of the stromal vascular fraction (SVF) of autologous adipose tissue to treat osteoarthritis has been used for several years demonstrating its safety and noticeable efficacy. This article presents clinical data from patients afftected by moderate and severe knee osteoarthritis demonstrating safety and clinical efficacy of the treatment when this autologous cell product is injected in the knee joint and patients evaluated post-operatively after 1?year. However, what do we know about the mechanism that underlies this clinical improvement? This article proposes, for the first time in our opinion, a hypothesis of the mode of action that involves structural and molecular interactions between SVF and infrapatellar fat pad (IFP). As consequence, there would be a re-education of intra-articular adipose tissue, which we consider a key player for the clinical effect observed in the mid and long term mainly due to immuno-regulatory mechanisms. METHODS:This is a retrospective and not controlled study that evaluated 50 patients (100 joints) ranging from 50 to 89?years old, separated by age cohorts. Clinical efficacy was assessed using the Lequesne, WOMAC, and VAS scales, by ultrasound control and quantification of the biochemical profiles of synovial fluid. RESULTS:There were no serious adverse effects. All the indexes studied showed a significant clinical improvement after 1-year follow-up for all ages and OA degree groups. This finding was correlated with the ultrasound observations and biochemical data, which show a marked decrease in catabolic and pro-inflammatory molecules (MMP-2, IL-1B, IL-6, and IL-8) and significant increase for anabolic and anti-inflammatory molecules (IGF-1 and IL-10). CONCLUSIONS:We conclude that intra-articular SVF infiltration for knee OA treatment is safe and effective during 1?year. We propose that applied SVF cells cause a cascade of molecular and structural events that, through complex interactions between IFP and SVF, re-educating the intra-articular fatty tissue towards a homeostatic, protective, and anti-inflammatory function, which will ultimately promote the restructuring and regeneration of damaged tissues.

Project description:ObjectiveThe aim of this work was to report the prevalence of computed tomography (CT)-detected intra-articular mineralization.DesignWe included participants from the Multicenter Osteoarthritis (MOST) Study. At the 12th year visit of the MOST study, bilateral knee CTs were first obtained. All participants also had posteroanterior and lateral radiographs of bilateral knees and completed standard questionnaires. Knee radiographs were assessed for Kellgren & Lawrence grade (KLG) and radiographic evidence of intra-articular mineralization. CT images were scored using the Boston University Calcium Knee Score (BUCKS) for cartilage, menisci, ligaments, capsule, and vasculature. Prevalence of intra-articular mineralization was computed for the total sample, and stratified by age, sex, race, Body Mass Index (BMI), presence of frequent knee pain, and KLG. We also determined distribution of mineralization in the cartilage and meniscus, and co-localization.Results4140 bilateral knees from 2070 participants were included (56.7% female, mean age 61.1 years, mean BMI: 28.8 kg/m2). On radiographs 240 knees (5.8%) had intraarticular mineralization, while CT-detected mineralization was present in 9.8% of knees. Prevalence of hyaline articular and meniscus mineralization increased with age and KL grade, and was similar by sex, BMI categories, and comparable in subjects with and without frequent knee pain. Mineralization tended to be ubiquitous in the joint, most commonly involving all three (medial/lateral tibiofemoral and patellofemoral) compartments (3.1%), while the patellofemoral compartment was the most involved compartment in isolation (1.4%).ConclusionsCT of the knee provides greater visualization of intra-articular mineralization than radiographs and allows better localization of the crystal deposition within the joint. Further studies should focus on the co-localization of intra-articular crystal deposition and corresponding magnetic resonance imaging (MRI)-features of knee osteoarthritis (OA).

Project description:BackgroundIntra-articular (IA) corticosteroid (CS) injections are the mainstay of treatment for symptomatic management in knee osteoarthritis (OA), particularly in the UK. IA platelet-rich plasma (PRP) injections are a promising alternative, but no systematic reviews to date have compared them to the current standard of care, IA CS injections. We aim to investigate the effect of IA PRP injections versus IA corticosteroid injections for the symptomatic management of knee OA.MethodsAll published trials comparing IA PRP and CS injections for knee OA were included. MEDLINE, EMBASE, Scopus and Web of Science were searched through June 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool. A random effects model was used to calculate standardized mean difference with 95% confidence interval in WOMAC/VAS score (or subscores), comparing IA PRP to CS injections across studies.ResultsIncluded were eight studies and 648 patients, 443 (68%) were female, mean age 59 years, with a mean BMI of 28.4. Overall, the studies were considered at low risk of bias. Compared with CS injections, PRP was significantly better in reducing OA symptoms (pain, stiffness, functionality) at 3, 6 and 9 months post-intervention (P < 0.01). The greatest effect was observed at 6 and 9 months (- 0.78 (- 1.34 to - 0.23) standard mean deviations (SMD) and - 1.63 (- 2.14 to - 1.12) SMD respectively). At 6 months, this equates to an additional reduction of 9.51 in WOMAC or 0.97 on the VAS pain scales. At 6 months PRP allowed greater return to sporting activities than CS, measured by the KOOS subscale for sporting activity, of magnitude 9.7 (- 0.45 to 19.85) (P = 0.06). Triple injections of PRP, generally separated by a week, were superior to single injections over 12 months follow-up (P < 0.01).ConclusionsIA-PRP injections produce superior outcomes when compared with CS injections for symptomatic management of knee OA, including improved pain management, less joint stiffness and better participation in exercise/sporting activity at 12 months follow-up. Giving three IA-PRP, with injections separated by a week, appears more effective than 1 IA-PRP injection.Prospero trial registration numberCRD42020181928 .

Project description:BackgroundRecently, in an open pilot study, we found up to two years, a potential pain-relieving effect of intra-articular gold micro-particles using the patient's synovial fluid for patients with knee osteoarthritis (KOA). During the study the excluded group of patients, due to multisite pain, co-morbidities, and other exclusion criteria., received intra-articular gold micro-particles using hyaluronic acid,. We aimed to identify if pre-treatment characteristics influence the global outcome two years after intra-articular treatment for painful KOA with gold microparticles using hyaluronic acid.MethodsUsing hyaluronic acid as the carrier, 136 patients with KOA received intraarticular injections with 20 mg gold microparticles (72.000 particles, 20-40 μm in diameter). In the analysis, we included the Global Rating of Change Scale, Pain Detect Questionnaire (PDQ), Body Mass Index (BMI), and Kellgren & Lawrence score at the inclusion, Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) sub-scores for pain, stiffness, and function at inclusion and two years.ResultsOn the Global Rating Change Scale, 69.1% of patients reported a positive effect, 28.7% no effect, and 2.2% worse. PDQ and the three WOMAC subscores all improved at two years of follow-up. PDQ ≥ 13 (P = 0.028), BMI (P = 0.022) and Kellgren & Lawrence grade 4 (P = 0.028) at inclusion reduced the effect with a minor odds ratio compared to the baseline effect of treatment (P = 0.025). WOMAC subscores at inclusion did not influence the outcome (P > 0.5).ConclusionsSevere osteoarthritis, obesity, and neuropathic pain, reduced the effect of intra-articular gold microparticles for knee OA.Trial registrationThe study followed the principles of the Declaration of Helsinki and was approved by the local ethics committee of the North Denmark Region by 27/07/2016 (N-20,160,045). The regional data protection agency approved the project by 06/07/2016 (2008-58-0028, ID 2016 - 116) and registered in ClinicalTrial.Gov by 04/01/2018 (NCT03389906).

Dataset Information

Structural effects of intra-articular TGF-?1 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial.

Publications

Structural effects of intra-articular TGF-β1 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial.

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