Intra-articular Hyaluronan Research Articles

PATIENT PERSPECTIVES ON ORTHOBIOLOGICS FOR OSTEOARTHRITIS

Disease modifying approaches are commonly applied in OA patients. An aging society with better life expectancies is increasing in Europe and the globe. Orthobiologics cover intraarticular hyaluronan injections and also cellular therapies. Cellular therapies range from platelet rich plasma (PRP) applications to exosomes. Short term follow-up of limited number of patients revealed favorable results in clinical cellular therapies. Most of these studies evaluated decrease of pain and increase in function. Recent basic science studies focused on the action mechanism of orthobiologic therapies however patient perspective is less studied. Our research team has recently performed a qualitative study on the patient perspective of hyaluronan injection of the knee joint. Findings of that study will be shared and future patient knowledge based options on orthobiologics will be discussed.

Comparative effectiveness of pharmacological interventions for hand osteoarthritis: a systematic review and network meta-analysis of randomised trials

ObjectiveTo explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA).MethodsWe systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021,...

Retraction Note: Effect of a single intra-articular high molecular weight hyaluronan in a naturally occurring canine osteoarthritis model: a randomized controlled trial

Retraction Note: Effect of a single intra-articular high molecular weight hyaluronan in a naturally occurring canine osteoarthritis model: a randomized controlled trial

Efficacy and Safety of Intra-Articular Cross-Linked Sodium Hyaluronate for the Treatment of Knee Osteoarthritis: A Prospective, Active-Controlled, Randomized, Parallel-Group, Double-Blind, Multicenter Study.

The safety and efficacy of Hyruan ONE (test product), an intra-articular cross-linked sodium hyaluronate injection, to treat mild-to-moderate knee osteoarthritis was compared with that of Durolane (comparator) in a prospective, active-controlled, parallel-group, double-blind (masked-observed), multicenter non-inferiority study. European patients (n = 284) were randomized 1:1 (test product:comparator) and received one injection of cross-linked hyaluronic acid (60 mg/3 mL). In total, 280 patients completed the study. The primary endpoint of mean change in Western Ontario and McMaster University (WOMAC)-Likert Pain sub-scores from baseline at week 13 revealed changes of -5.59 and -5.54 for the test and comparator groups, respectively, demonstrating non-inferiority of the test product (difference, -0.05 [95% confidence interval, -0.838 to 0.729]). Secondary endpoint results, which included changes in WOMAC-Likert Pain sub-score from baseline to 26 weeks post-injection and changes in WOMAC-Likert Total score and Physical Function and Stiffness sub-scores, changes in patients' and investigators' global assessments, use of rescue medication, and responder rates at 13 and 26 weeks post-injection were similar between the groups. Incidence of adverse events was also similar. In both groups, most treatment-emergent adverse events were mild/moderate. Hyruan ONE was non-inferior to the comparator at 13 weeks post-injection in European patients with mild-to-moderate knee osteoarthritis.

RADIOGRAPHIC COMPARATIVE REGENERATIVE EFFECTS OF HYALURONATE AND PIROXICAM IN OSTEOARTHRITIS MODELS OF RATS

Background: Osteoarthritis is the most common degenerative joint disease that affects commonly in old age. Standard treatment of this disease is still underdeveloped, however multiple drug groups delay progression or reduce the symptoms. Objective of this study was to assess and compare the regenerative effects of hyaluronate and piroxicam in a rat model of osteoarthritis at the radiographic level. Methods: This laboratory-based randomized trial was conducted at Department of Pharmacology Army Medical College, Rawalpindi, from May to July 2019. Resection of the medial meniscus and anterior cruciate ligament resulted in osteoarthritis in the right knee joints of 24 rats. They were separated into 3 groups of 8 rats each. For 4 weeks, groups I, II, and III received intra-articular saline, hyaluronate, and piroxicam, respectively. After one week, radiographs of the anaesthetized rats’ matching knee joints were collected. Results: Comparison of radiograph of control group with drug treated group confirmed regenerative effects of hyaluronate and piroxicam (p=0.001). However comparison of hyaluronate and piroxicam treated groups had p=0.335 that professed both drug have equal regenerative effects in rat model of osteoarthritis. Conclusion: In a rat model of osteoarthritis, intra-articular injection of hyaluronate acid and piroxicam had regenerating benefits at the radiological level. Both administered medicines had similar regeneration effects. Pak J Physiol 2022;18(3):19–22

Do Glucocorticoid Injections Increase the Risk of Knee Osteoarthritis Progression Over 5 Years?

Recent findings have demonstrated that intraarticular (IA) glucocorticoid injections can be deleterious for knees with osteoarthritis (OA). This study was undertaken to assess, in a real-life setting, the risk of knee OA progression in patients who received IA glucocorticoid injections over a 5-year follow-up period. We used marginal structural modeling with inverse probability of treatment weighting to determine the causal association between IA glucocorticoid injections and the 5-year risk of disease progression in patients with symptomatic knee OA from the Knee and Hip Osteoarthritis Long-term Assessment cohort. OA progression was defined as an incident total knee replacement (TKR) and/or radiographic worsening (Kellgren/Lawrence [K/L] grade or joint space narrowing [JSN]). We also examined these outcomes in knees that received IA hyaluronan (IAHA) injections. Among the 564 patients with knee OA included in the study sample, 51 (9.0%) and 99 (17.5%) received IA glucocorticoid or IAHA injections, respectively, and 414 (63.1%) did not receive any injection during follow-up. Compared to untreated knees, those treated with IA glucocorticoid injections had a similar risk of incident TKR (hazard ratio [HR] 0.92 [95% confidence interval (95% CI) 0.20, 4.14]; P = 0.91) or K/L grade worsening (HR 1.33 [95% CI 0.64, 2.79]; P = 0.44). IAHA injections had no effect on the risk of TKR (HR 0.81 [95% CI 0.14, 4.63]; P = 0.81) or K/L grade worsening (HR 1.36 [95% CI 0.85, 2.17]; P = 0.20). Similar results were obtained for JSN, and when TKR and radiographic outcomes were combined. In this study, IA glucocorticoid injections for symptomatic knee OA did not significantly increase the 5-year risk of incident TKR or radiographic worsening. These findings should be interpreted cautiously and replicated in other cohorts.

Cooled radiofrequency ablation of the genicular nerves for chronic pain due to osteoarthritis of the knee: a cost-effectiveness analysis compared with intra-articular hyaluronan injections based on trial data

BackgroundEffective symptom control in painful knee osteoarthritis (OA) may improve patient quality of life. In a randomised crossover trial (NCT03381248), COOLIEF* cooled radiofrequency ablation (CRFA) reduced pain and stiffness and improved physical function and quality of life compared with intra-articular hyaluronan (HA) injections. The present study aimed to establish the cost effectiveness of CRFA versus intra-articular HA injections for treating moderate-to-severe OA knee pain from a US Medicare perspective.MethodsWe conducted a cost-effectiveness analysis using utility data (EQ-5D) from the randomised crossover trial of CRFA versus intra-articular HA injections, which had follow-ups at 1, 3, 6, and 12 months. Patients in the HA group with unsatisfactory outcomes (e.g., continued pain) at 6 months could cross over to CRFA. Economic analysis outcomes included quality-adjusted life-years (QALYs), costs, and cost effectiveness (cost per QALY gained). Base-case analyses were modelled on a 6-month time horizon (to trial crossover). Due to limited trial data in the HA arm beyond 6 months, scenarios explored potential outcomes to 12 months if: 1) Utility with HA persisted for a further 6 months; 2) A second HA injection was received at 6 months and achieved the same utility change for the second 6 months. In both scenarios, the CRFA arm used trial data for patients who received CRFA from baseline to 12 months. Alternative costing scenarios were also explored.ResultsCRFA resulted in an incremental QALY gain of 0.020 at an incremental cost of US$1707, equating to an incremental cost-effectiveness ratio (ICER) of US$84,392 per QALY over 6 months, versus intra-articular HA injections. Extending the analysis to 12 months and assuming persistence in utility in the HA arm resulted in a larger utility gain for CRFA (0.056 QALYs) and a lower ICER of US$30,275 per QALY. If patients received a second HA injection, the incremental benefit of CRFA out to 12 months was reduced (QALY gain 0.043) but was offset by the costs of the second HA injection (incremental cost US$832). This resulted in an ICER of US$19,316 per QALY.ConclusionsCRFA is a cost-effective treatment option for patients with OA-related knee pain considering the typical US threshold of US$100,000/QALY.

The Adverse Effects and Efficacy of Mixing Local Anesthesia Drug to Intra-Articular Hyaluronate Linked with Diclofenac Injection as the One-Shot for Osteoarthritis of the Knee

The Adverse Effects and Efficacy of Mixing Local Anesthesia Drug to Intra-Articular Hyaluronate Linked with Diclofenac Injection as the One-Shot for Osteoarthritis of the Knee

The Effects of Intra-Articular Hyaluronate Injections in Young (<55 years) Patients with Glenohumeral Joint Osteoarthritis

Purpose Glenohumeral joint (GHJ) osteoarthritis (OA) in younger patients represents a challenging problem. This study assessed the efficacy of intra-articular hyaluronate injection in patients below the age of 55 years. Methods We reviewed our patient database from August 2013 to December 2016 for patients who received a fluoroscopic-guided intra-articular injection of hyaluronate. Those who had received interventional procedures within the preceding 12 months were excluded. We evaluated the response to the injection using the Oxford Shoulder Score (OSS). These scores were recorded before injection and at 6 weeks, 12 weeks, and 26 weeks postinjection. Radiographs were reviewed independently by two evaluators, and the severity of GHJ OA was categorized (mild, moderate, or severe) using the Samilson–Prieto classification. Results Fifty-five patients were identified, with a mean age of 43 years (18.6–54.6 years). These cases were classified as being mild in 11 (20%), moderate in 21 (38%), and severe in 23 (42%) using Samilson-Prieto classification. In the severe group, there was a statistically significant improvement in the OSS at all time points. In the moderate group, there were statistically significant improvements at 6 weeks and 12 weeks but not at 6 months. In the mild group, there were no statistically significant changes. Conclusion In patients under the age of 55 years with moderate-to-severe GHJ OA, there is a significant improvement in the OSS up to 12 weeks after intra-articular injection of hyaluronate, with improvements lasting up to 26 weeks in more severe cases. Hyaluronate is, therefore, a useful treatment option in younger patients and may potentially delay the need for arthroplasty.

Effects and Safety of Intra-Articular Sodium Hyaluronate Injection for the Treatment of Ankle Osteoarthritis: A Prospective Clinical Trial

Various nonoperative treatments have been implemented to reduce pain and improve the quality of life in patients with ankle osteoarthritis. Among these treatments, intra-articular hyaluronate injection has proven efficacy and safety in patients with knee osteoarthritis. The purpose of this study was to evaluate the efficacy and complications of hyaluronate injection using various clinical scoring systems. This study included 37 patients with unilateral ankle osteoarthritis (grade 2 or 3 according to the Takakura classification) who did not respond to previous pharmacological treatment. 3 weekly hyaluronate injections (2 mL Hyruan Plus®) were administered. The efficacy of intra-articular hyaluronate injection was evaluated on the basis of patient-reported foot and ankle clinical assessment at a mean follow-up of 13.8 ± 8.3 (range 6-33) months. Ankle Osteoarthritis Scale scores for pain and disability, American Orthopedic Foot and Ankle Society ankle-hindfoot scores, and visual analog scale for pain significantly improved at the final follow-up compared to that before intra-articular hyaluronate injection (p ≤ .05). When patients were dichotomized according to age, sex, body mass index, symptom duration, and Takakura classification, all these factors were not related to clinical outcomes. This study suggests that 3 weekly intra-articular hyaluronate injections can be performed safely to reduce pain and improve function without serious complications in patients with early or intermediate-grade ankle osteoarthritis when patients inadequately respond to medication. Larger controlled studies are needed to clarify the effects of hyaluronate injection and identify patients who can benefit most from hyaluronate injection.

RETRACTED ARTICLE: Effect of a single intra-articular high molecular weight hyaluronan in a naturally occurring canine osteoarthritis model: a randomized controlled trial

BackgroundOsteoarthritis (OA) is a complex joint disease and chronic pain source, affecting a patient’s quality of life and posing a financial burden. As the dog is considered a nearly ideal species for translation research of human OA and the most used model for research, exploring spontaneous dog OA under the One Health/One Medicine concept can improve both humans and dogs’ health and well-being.MethodsIn a clinical treatment experiment, forty (N=40) joints were selected and randomly assigned to a control group (CG), which received 0.9% NaCl or a treatment (HG), which received Hylan G-F 20. Evaluations were performed on treatment day (T0), 8, 15, 30, 90, and 180 days post-treatment. They consisted of four different Clinical Metrology Instruments (CMI), evaluation of weight distribution, joint range of motion, thigh girth, radiographic and digital thermography imaging, synovial fluid interleukin-1 (IL-1), and C-reactive protein concentrations. Results were compared with repeated measures ANOVA, with a Huynh-Feldt correction, Paired samples T-test, or Wilcoxon signed-ranks test, with p<0.05.ResultsPatients had a mean age of 6.5±2.4 years and a bodyweight of 26.6±5.2kg, and joints graded as mild (n=28, 70%), moderate (n=6, 15%), and severe OA (n=6, 15%). No differences were found between groups at T0. Symmetry index and deviation showed significant improvements in HG from 30 days (p<0.01) up to 180 days (p=0.01). Several CMI scores, particularly pain scores, improved from 90 to 180 days. Radiographic signs progressed in both groups. In both groups, increasing body weight and age corresponded to worse clinical presentation. IA hyaluronan administration produced increased lameness in six cases, which resolved spontaneously.ConclusionsThis study characterizes the response to treatment with Hylan G-F 20, which can produce significant functional and pain level improvements in patients with OA, even those with factors related to worse response to treatment.

Single intra-articular injection of a novel stabilized cross-linked hyaluronate in the treatment of knee osteoarthritis: compared with a united states-approved similar

Purpose: Nowadays, intra-articular hyaluronate (IAHA) injection is one of the common treatments to improve the symptoms of knee osteoarthritis (OA). A recent meta-analysis showed that the most effective and safe HA products were those that derive HA from biological fermentation and have a molecular weight ≧3000kDa. Through cross-linked technique, the molecular weight of HA can be amplified to near infinity, and the time HA remains in the knee also can be prolonged, potentially increasing the efficacy and duration of the treatment effects and providing a single-injection choice.

Comparing efficacy of intraarticular single crosslinked Hyaluronan (HYAJOINT Plus) and platelet-rich plasma (PRP) versus PRP alone for treating knee osteoarthritis

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.

Effect of Intra-articular Triamcinolone vs Hyaluronate Injection in Zygapophyseal Joint Arthropathy: A Prospective Randomized Controlled Trial

Effect of Intra-articular Triamcinolone vs Hyaluronate Injection in Zygapophyseal Joint Arthropathy: A Prospective Randomized Controlled Trial

Measures of Adult Knee Function.

Measures of Adult Knee Function.

Shea Nut Oil Extracts Enhance the Intra-Articular Sodium Hyaluronate Effectiveness on Surgically Induced OA Progression in Rats.

Osteoarthritis (OA) progression is associated with joint pain and stiffness. Intra-articular hyaluronic acid (IAHA) injection in knee OA restores the viscoelasticity of the joint and prevents cartilage damage. Shea nut oil extract (SNO) was shown to provide chondroprotection on surgically-induced OA progression in rats. Here we aim to examine IAHA injection supplemented with SNO diet for a synergetic evaluation on the disease progression in OA rats. We employed an anterior cruciate ligament transection plus medial meniscectomy-induced knee OA rat model with up to 12 weeks of sign/behavior observation (knee width, weight-bearing) and histological assessments of joint damage. We found both IAHA and SNO alone significantly attenuated histological changes of cartilage degeneration and synovial reactions in these knee OA rats. Nonetheless, oral SNO alone mitigated OA pain and inflammation while IAHA alone had no significant impact on the weight-bearing test and knee joint swelling. Moreover, with IAHA-treated rats fed with oral SNO diet, additional anti-inflammatory and anti-nociceptive effects were found, which further enhanced and maintained IAHA protection. Given the differential phenotype of oral SNO vs. IAHA, a regimen of IAHA coupled with SNO supplement provides a long-term effect of IAHA treatment. Taken together, the SNO supplement can be safely used as an adjuvant diet for chronic symptomatic relief of OA coupled with IAHA management.

DIAGNOSIS DAN TATALAKSANA KOMPREHENSIF OSTEOARTRITIS

DIAGNOSIS DAN TATALAKSANA KOMPREHENSIF OSTEOARTRITIS

Intra-articular Hyaluronan Therapy for Symptomatic Knee Osteoarthritis

Intra-articular hyaluronan therapy (IAHA) is a common but controversial nonsurgical treatment of symptomatic knee osteoarthritis. The overall treatment effect of IAHA for osteoarthritis pain is substantial, but the majority of this benefit is mediated by the placebo effect. Despite the large overall benefit of IAHA when the effect of the hyaluronan is combined with the placebo effect, there is only a small benefit of questionable clinical significance of IAHA compared with intra-articular placebo. Compared with intra-articular corticosteroids, however, IAHA most likely is comparable for long-term pain relief and possibly slightly inferior for short-term pain relief.

Evaluation of the effect of experimentally induced cartilage defect and intra-articular hyaluronan on synovial fluid biomarkers in intercarpal joints of horses

BackgroundInflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and thus diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injection, alone or in combination with other substances, has been examined only in a few equine studies. The effects of hyaluronan on some pro-inflammatory mediators, such as prostaglandin E2, have been documented but especially the effects on synovial fluid anti-inflammatory mediators are less studied. In animal models hyaluronan has been demonstrated to reduce pain via protecting nociceptive nerve endings and by blocking pain receptor channels. However, the results obtained for pain-relief of human osteoarthritis are contradictory. The aim of the study was to measure the synovial fluid IL-1ra, PDGF-BB, TGF-β1 and TNF-α concentrations before and after surgically induced cartilage defect, and following intra-articular hyaluronan injection in horses. Eight Standardbred horses underwent bilateral arthroscopic surgeries of their intercarpal joints under general anaesthesia, and cartilage defect was created on the dorsal edge of the third carpal bone of one randomly selected intercarpal joint of each horse. Five days post-surgery, one randomly selected intercarpal joint was injected intra-articular with 3 mL HA (20 mg/mL).ResultsOperation type had no significant effect on the synovial fluid IL-1ra, PDGF-BB, TGF-β1 and TNF-α concentrations but compared with baseline, synovial fluid IL-1ra and TNF-α concentrations increased. Intra-articular hyaluronan had no significant effect on the biomarker concentrations but a trend of mild improvement in the clinical signs of intra-articular inflammation was seen.ConclusionsCreation of the cartilage defect and sham-operation lead to an increase of synovial fluid IL-1ra and TNF-α concentrations but changes in concentrations of anabolic growth factors TGF-β1 and PDGF-BB could not be documented 5 days after the arthroscopy. Intra-articular hyaluronan was well tolerated. Further research is needed to document possible treatment effects of intra-articular hyaluronan on the synovial fluid biomarkers of inflammation and cartilage metabolism.

Budget impact analysis of viscosupplementation for non-surgical treatment of knee osteoarthritis

Knee osteoarthritis affects 3.8% of the world population and manifests as pain, edema, stiffness, and reduced joint function, impacting the patient's quality of life. Treatment consists of the pharmacological, non-pharmacological, and surgical modalities. Viscosupplementation (intraarticular hyaluronate) has been proposed to relieve symptoms and potentially postpone surgery. This study estimated the budget impact of the association of this drug and non-surgical treatment (standard treatment) from the perspective of the Brazilian Unified National Health System. Based on the assumption that 5% of patients proceed to treatment and on the direct costs of the pharmacological and non-pharmacological modalities, the authors calculated the reference and alternative scenarios that compared the different treatment options in a three-year timeline. The principal analysis estimated an incremental budget impact of approximately BRL 126 million (U$ 32 million) for one vial of hyaluronate a year and BRL 252 million (USD 64 million) for two vials a year. Diacerein, an oral chondroprotector, assessed as an alternative, showed a budget impact of BRL 334 million (USD 86 million) in relation to standard treatment, representing a 24% cost increase compared to two vials a year of hyaluronate, making it less economically advantageous. Viscosupplementation can provide better quality of life for patients, reduce costs for the health system, and optimize the flow of care in health services. The estimates presented in this study can assist administrators in the best use of resources and thus in decision-making on the technology's incorporation.