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A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project.

ABSTRACT: OBJECTIVE: AMELIA (OsteoArthritis Modifying Effects of Long-term Intra-articular Adant) was designed to compare against placebo the efficacy and safety of repeated injections of hyaluronic acid (HA) and its effect on disease progression over 40 months. METHODS: A multicentre, randomised, patient and evaluator-blinded, controlled study in 306 patients fulfilling American College of Rheumatology criteria for knee osteoarthritis, radiological grades II-III (Kellgren-Lawrence) and joint space width ? 2 mm. Patients received four cycles of five intra-articular HA or placebo injections with a follow-up of 6 months after the first and second cycles, and 1 year after the third and fourth cycles. Osteoarthritis Research Society International (OARSI) 2004 responder criteria were used to assess efficacy. The consumption of rescue medication was a secondary outcome. Adverse events were recorded for safety purposes. RESULTS: At the 40-month visit significantly more patients responded to HA compared with placebo (OARSI 2004, p=0.004). The number of responders to HA increased through the study, whereas those to placebo did not change. Significant differences were also found in favour of HA for each individual component of the OARSI 2004. No safety problems were recorded. CONCLUSIONS: The results of AMELIA offer pioneer evidence that repeated cycles of intra-articular injections of HA not only improve knee osteoarthritis symptoms during the in-between cycle period but also exert a marked carry-over effect for at least 1 year after the last cycle. In this respect, it is not possible to establish if this carry-over effect reflects true osteoarthritis remission or just a modification of the disease's natural course. ClinicalTrials.gov number, NCT00669032.

SUBMITTER: Navarro-Sarabia F

PROVIDER: S-EPMC3184238 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project.

Navarro-Sarabia F F Coronel P P Collantes E E Navarro F J FJ de la Serna A Rodriguez AR Naranjo A A Gimeno M M Herrero-Beaumont G G

Annals of the rheumatic diseases 20110817 11

<h4>Objective</h4>AMELIA (OsteoArthritis Modifying Effects of Long-term Intra-articular Adant) was designed to compare against placebo the efficacy and safety of repeated injections of hyaluronic acid (HA) and its effect on disease progression over 40 months.<h4>Methods</h4>A multicentre, randomised, patient and evaluator-blinded, controlled study in 306 patients fulfilling American College of Rheumatology criteria for knee osteoarthritis, radiological grades II-III (Kellgren-Lawrence) and joint ...[more]

PMID: 21852252

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Project description:BACKGROUND:Some controversy exists regarding the safety of intra-articular hyaluronic acid (IAHA) in the management of osteoarthritis (OA). OBJECTIVE:The objective of this study was to re-assess the safety profile of IAHA in patients with OA, through a comprehensive meta-analysis of randomized, placebo-controlled trials. METHODS:A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with IAHA in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, cardiac, vascular, respiratory, nervous system, skin and subcutaneous tissue disorders, musculoskeletal, renal and urinary disorders, infections and infestations, and hypersensitivity reaction. RESULTS:Database searches initially identified 1481 records. After exclusions according to the selection criteria, 22 studies were included in the qualitative synthesis, and nine studies having adequate data were ultimately included in the meta-analysis. From the studies excluded according to the pre-specified selection criteria, 21 with other pharmacological OA treatments permitted during the trials were a posteriori included in a parallel qualitative synthesis, from which eight studies with adequate data were finally included in a parallel meta-analysis. Since this meta-analysis was designed to assess safety, the exclusion criterion on concomitant anti-OA medication was crucial. However, due to the high number of studies that allowed mainly concomitant oral non-steroidal anti-inflammatory drugs (NSAIDs), we decided to include them in a post hoc parallel analysis in order to compare the results from the two analyses. No statistically significant difference in odds was found between IAHA and placebo for all types of SOC-related disorders, except for infections and infestations, for which significantly lower odds were found with IAHA compared with placebo, both overall (odds ratio [OR]?=?0.61, 95% confidence interval [CI] 0.40-0.93; I2?=?0%) and in studies without concomitant anti-OA medication (OR?=?0.49, 95% CI 0.27-0.89). There were significant increased odds of reporting serious AEs with IAHA compared with placebo, both overall (OR?=?1.78, 95% CI 1.21-2.63; I2?=?0%) and in studies with concomitant anti-OA medication (OR?=?1.78, 95% CI 1.10-2.89), but not in studies without concomitant anti-OA medication (OR?=?1.78, 95% CI 0.92-3.47). CONCLUSIONS:Using the available data on studies without any concomitant anti-OA medication permitted during clinical trials, IAHA seems not to be associated with any safety issue in the management of OA. However, this evidence was associated with only a "low" to "moderate" certainty. A possible association with increased risk of serious AEs, particularly when used with concomitant OA medications, requires further investigation.

Project description:OBJECTIVES:This study aimed to describe patients treated for knee osteoarthritis between 2006 and 2013 in France and to compare the delay from diagnosis to total knee replacement between patients who received intra-articular hyaluronic acid injections and those who did not receive the injections. A second objective was to compare direct medical costs for ambulatory care between treatment groups. MATERIALS AND METHODS:Patients were selected from a representative sample of the real world administrative claims database using an algorithm developed by experts from the scientific committee of the study. Data were matched with the medico-administrative database for hospital care. A Cox proportional hazards model was stratified for the treatment group and adjusted for available socio-demographic and medical covariates to compare restricted mean survival times at different time points (1, 3, 5 and 7.5 years) between groups. Costs were expressed in 2013 euros. RESULTS:A total of 14,782 patients were treated for knee osteoarthritis (67% women; mean age = 68 years). Among this population, 1,662 patients had total knee replacement (11.2%). At each time point, restricted mean survival time without total knee replacement was significantly higher (p-values<0.001) for hyaluronic acid group, from +51 to +217 days at 1 and 7.5 years, respectively. For the year preceding total knee replacement, the means for total direct medical costs were similar between groups, €744 vs €805 for treatment and control groups, respectively, (p-value = 0.104). Intra-articular injections accounted for less than 10% of the total costs. CONCLUSION:This is the first retrospective longitudinal study involving knee osteoarthritis patients using medico-administrative databases in France. The results support the effectiveness of hyaluronic acid injections in delaying total knee replacement and show that patients treated with hyaluronic acid have similar direct medical costs for ambulatory care compared to patients treated with corticosteroids only.

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:The aim of the present study was to compare the clinical and economic benefits of intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA) in Chinese patients with knee osteoarthritis (OA). A total of 86 patients (42 treated with PRP and 44 with HA) were treated with three weekly intra-articular injections. The inclusion criteria included patients between 18 and 75 years of age, with chronic knee pain or swelling lasting >3 months and X-ray findings of degenerative joint alterations according to the Kellgren-Lawrence score grade I-III. Clinical examinations were performed before treatment, at 1- and 6-month post-injection intervals. International Knee Documentation Committee subjective, Western Ontario and McMaster Universities and visual analogue scale scores were determined at each examination. Adverse reactions, average cost, treatment time and patient satisfaction were also recorded. Compared with patients injected with HA, PRP was found to be associated with increased and more severe post-injection pain and swelling, where the duration of adverse reactions was greater in the PRP group (P=0.02). During the follow-up evaluations, both groups showed statistically significant improvements in all clinical scores from pre-injection to 1- and 6-month assessments (P<0.05). However, no significant inter-group (PRP vs. HA) differences were observed in the clinical scores between the two follow-up time points. There were also no significant differences in clinical score between the groups with regards to the Kellgren-Lawrence grade I, II or III. The average cost of PRP injections was 22.8X that of HA administration and the average treatment time was 5X that of HA, but there was no significant difference in patient satisfaction. These preliminary results indicate that although PRP injections can significantly improve clinical outcome in patients with knee OA, PRP is not any more effective compared with HA. Furthermore, PRP injections are associated with higher costs and treatment times. Therefore, additional clinical studies are required before PRP injections can be considered as a first-line treatment option for knee OA.

Project description:Arthritic diseases, such as osteoarthritis and rheumatoid arthritis, inflict an enormous health care burden on society. Osteoarthritis, a degenerative joint disease with high prevalence among older people, and rheumatoid arthritis, an autoimmune inflammatory disease, both lead to irreversible structural and functional damage to articular cartilage. The aim of this study was to investigate the effect of polyphenols such as catechin, quercetin, epigallocatechin gallate, and tannic acid, on crosslinking type II collagen and the roles of these agents in managing in vivo articular cartilage degradation. The thermal, enzymatic, and physical stability of bovine articular cartilage explants following polyphenolic treatment were assessed for efficiency. Epigallocatechin gallate and tannic acid-treated explants showed >12 °C increase over native cartilage in thermal stability, thereby confirming cartilage crosslinking. Polyphenol-treated cartilage also showed a significant reduction in the percentage of collagen degradation and the release of glycosaminoglycans against collagenase digestion, indicating the increase physical integrity and resistance of polyphenol crosslinked cartilage to enzymatic digestion. To examine the in vivo cartilage protective effects, polyphenols were injected intra-articularly before (prophylactic) and after (therapeutic) the induction of collagen-induced arthritis in rats. The hind paw volume and histomorphological scoring was done for cartilage damage. The intra-articular injection of epigallocatechin gallate and tannic acid did not significantly influence the time of onset or the intensity of joint inflammation. However, histomorphological scoring of the articular cartilage showed a significant reduction in cartilage degradation in prophylactic- and therapeutic-groups, indicating that intra-articular injections of polyphenols bind to articular cartilage and making it resistant to degradation despite ongoing inflammation. These studies establish the value of intra-articular injections of polyphenol in stabilization of cartilage collagen against degradation and indicate the unique beneficial role of injectable polyphenols in protecting the cartilage in arthritic conditions.

Project description:Purpose ?The aim of the study was to evaluate the clinical effects of HYADD® 4, an hydrogel based on a hyaluronic acid derivative, in patients with symptomatic knee osteoarthritis, on symptoms, and joint function. Methods ?This retrospective study of patients with Kellgren-Lawrence grade II to IV knee osteoarthritis (American College of Rheumatology criteria) enrolled patients who had received two infiltrations of HYADD® 4, (24 mg/3 mL) 1?week apart, and evaluated: pain at rest, pain with movement, change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score; change in nonsteroidal anti-inflammatory drugs (NSAIDs)/acetaminophen use; satisfaction with therapy; tolerability. Study duration was 6 months for all predefined endpoints, with a 6-month extension for pain symptoms only. Results ?After 6 months, all predefined endpoints were evaluable in 698 of 937 enrolled patients (74.5%). Mean WOMAC scores were reduced by 56.3% from baseline ( p ?<?0.05). NSAIDs/acetaminophen use ?2 times/week (48.8% of patients at baseline) was substantially reduced after 1?month and was 19.6% after 6 months. After 6 months, 85.6% of patients were satisfied about efficacy. There were no significant adverse effects. The effect on resting pain was rapid, strong, and lasting: reduction from baseline was 45.1% at 1?month ( p ?<?0.05), 56.8% at 6 months ( p ?<?0.05), and 53.6% at 12 months ( p ?<?0.05). Pain on moving was reduced by 47.4% after 6 months ( p ?<?0.05) and 46.0% after 12 months ( p ?<?0.05), results at 6 and 12 months were similar. Conclusion ?HYADD® 4 is a new-generation hyaluronic acid with distinctive viscoelastic and rheological properties. In patients with mild-to-severe knee OA (Kellgren-Lawrence grades II-IV), two consecutive infiltrations 1?week apart reduced WOMAC scores and NSAIDs/acetaminophen consumption for at least 6 months. In a subpopulation ( n ?=?106), efficacy on pain lasted approximately 12 months. Adverse events were reported in 11.2% of patients; the most frequent were arthralgias. No cases of allergic reactions or systemic effects were recorded. Level of Evidence ?Level IV, retrospective case series.

Dataset Information

A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project.

Publications

A 40-month multicentre, randomised placebo-controlled study to assess the efficacy and carry-over effect of repeated intra-articular injections of hyaluronic acid in knee osteoarthritis: the AMELIA project.

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