Intra-articular Hyaluronic Acid Research Articles

Beyond Boundaries of a Trial: Post-Market Clinical Follow-Up of SOYA Patients

Background/Objectives: osteoarthritis (OA) is a leading cause of disability. With an aging population and rising obesity rates, OA presents a growing challenge to health systems worldwide. Current OA treatments involve a mix of pharmacological and nonpharmacological interventions. Viscosupplementation with hyaluronic acid (HA) has proven effective, especially in knee OA, leading to its recommendation in international guidelines. This study investigates the sustained benefits of a single intra-articular HA injection beyond one year in patients coming from the SOYA trial, considering the EU MDR 2017/745 emphasis on post-market follow-up. Methods: A prospective, observational, open, post-marketing study in a cohort of patients that participated in the SOYA trial. Follow-up was carried out by means of a telephone survey, and the data were anonymized and coded so that patients could not be identified. The study was approved by the Alcorcón Hospital Institutional Review Board (Alcorcón, Madrid, Spain). Results: In the follow-up of the SOYA trial, 81.5% of patients sustained positive effects for over 6 months after the trial ended. This correlated with improved daily functioning, enhanced mood, and high patient satisfaction. Younger age and milder OA grades were associated with prolonged treatment effects. Notably, 82% of patients with >6 months of improvement did not require additional medication. Conclusions: the results of this study support the safety and performance of Adant® Plus as a treatment for patients with mild and moderate knee OA, with results lasting more than one year. Post-marketing studies are particularly relevant to examine the experience gained with the use of the device in routine clinical practice.

Pain Management in Knee Osteoarthritis: Insights from an Exploratory Online Survey of Italian Patients and Physicians.

In Italy, knee osteoarthritis (KOA) accounts for over 5 million prevalent cases and requires long-term multidisciplinary management. The most frequent KOA symptom is pain. The aim of the survey is to provide a national overview of the current management of moderate-to-severe pain associated with KOA from both clinicians' and patients' perspectives. An exploratory qualitative survey was conducted in Italy between July and October 2023. The survey participants were members of four national scientific societies and two patient associations who were invited to participate via email and given an online questionnaire. Questions included a mix of single and multiple responses and scalar items. In total, 1473 clinicians and 150 patients with KOA completed the questionnaire. Patients rated knee pain as both the most burdensome symptom and the most frequent reason for treatment dissatisfaction and seeking consultation. One in two patients declared that they were unsatisfied/little satisfied with the current prescribed analgesic treatments. The clinicians surveyed preferentially prescribed intra-articular hyaluronic acid, oral non-steroidal anti-inflammatory drugs/paracetamol, non-pharmacological intervention, and intra-articular corticosteroids. The clinicians' selection of analgesic therapy often failed to adequately meet patients' expectations for pain relief. Our findings highlight the current unmet needs of patients with KOA in Italy and call for new approaches to effectively optimize the management of KOA-associated pain.

A retrospective claims data analysis of health care utilization and cost among patients receiving multi-injection intraarticular hyaluronic acid.

With the rising costs for knee arthroplasty, therapies that allow patients to avoid or delay surgery following knee osteoarthritis (KOA) may help in reducing overall health care costs. Multiple intraarticular hyaluronic acid (HA) products are available on the market, varying by formulation, molecular weight, and number of injections, but clinical and economic benefits may differ by product. OBJECTIVES: To evaluate the all-cause and KOA-related health care resource utilization (HCRU) and costs among newly diagnosed patients with KOA treated with multi-injection HA. A retrospective cohort study using a large commercial claims database (Merative MarketScan database) to identify patients with KOA treated with high molecular weight (HMW) (n = 11,200), medium molecular weight (MMW) (n = 10,225), or low molecular weight (LMW) HAs (n = 8,473) between 2016 and 2019. KOA-related and all-cause HCRU and costs were compared within 12 months after the index HA treatment date. The association between outcomes and HA treatments was evaluated using a doubly robust method to adjust for confounding factors. HCRU and costs among the propensity score-weighted HA groups were compared using generalized linear models. HMW HA patients were found to have lower adjusted KOA-related medical costs by $265.37 (P < 0.001) and pharmacy costs by $19.90 (P < 0.001) compared with LMW HA patients, as well as lower all-cause total medical costs by $130.42 (P = 0.013) and pharmacy costs by $63.33 (P < 0.001). HMW HA patients also had a lower adjusted KOA-related medical cost by $205.74 (P < 0.001) and pharmacy cost by $14.39 (P < 0.001) compared with MMW HA patients, as well as lower all-cause medical by $1,195.66 (P < 0.001) and pharmacy by $196.99 (P < 0.001). Three-injection treatment patients (HMW HA, 84%; MMW HA, 82%) had high completion rate, compared with the 5-injection treatment cohort (LMW HA, 48%). HMW HA patients had statistically significantly lower adjusted all-cause and KOA-related medical and pharmacy costs at 1 year follow-up compared with MMW HA and LMW HA patients. It is unclear if this is related to differences in molecular weight or specific mechanism of actions.

Could ASA and Charlson Comorbidity Index Scores Help the Current Comorbidities Stratification in Non-surgical Knee Osteoarthritis Multimodal Pain Management?

Non-surgical management of knee osteoarthritis emphasizes on multimodal approach according to patients subphenotypes (with or without comorbidities). Surgical treatment outcomes data suggest the role of ASA and Charlson Comorbidity Index (CCI) scores in the field. There are no comparative data on ASA and CCI stratification in non-surgical knee osteoarthritis pain management, which is the aim of our study. Eighty ASA 1–3 in-hospital patients, aged ≥ 36, treated for symptomatic chronic knee osteoarthritis with implemented intra-articular Betamethasone (7 mg/ml) or Hyaluronic acid (30 mg/2 ml), followed by as needed Dexketoprofen 50 mg i.v. or Paracetamol 1.0 g i.v., along with recommended 2 weeks (10 working days) exercise-based physiotherapy programme were examined retrospectively. Data regarding demographics, comorbidities, ASA low-risk(1–2)/high-risk(3), CCI low-risk(0–1/0–2)/high-risk(≥ 2/≥ 3) scoring subgroups, effusions, WBC, ESR, vital signs, clinical laboratory parameters, adverse events, and analgesic consumptions were collected as well. We tested the effect of different ASA and CCI scores on analgesic consumption (primary outcomes), and the effect of implemented risk-adjusted multimodal analgesia on subsequent participation or non-participation in the physiotherapy programme (secondary outcomes). Among all outcomes variables, ASA and CCI stratification confirmed only the higher age and ESR determinants in both the high-risk ASA 3 and high-risk CCI $ ≥ 2 subgroups, as well as more Hyaluronic acid applications in the elderly. The participants in the physiotherapy programme were mainly low-risk patients who received significantly more intra-articular Hyaluronic acid than Betamethasone. The ASA and CCI scores could help current (yes/no comorbidities) decision-making by implementing risk-adjusted pain management, emphasizing on severity rather than the type of comorbid conditions in non-surgical knee osteoarthritis population.

Is microfracture sufficient for high-tibial osteotomy, or should intra-articular hyaluronic acid and oral glucosamine-chondroitin be used as additional treatments?

BackgroundThis study aimed to compare the effects of microfracture (MF) versus intra-articular hyaluronic acid (HA) + oral glucosamine and chondroitin sulfate (GC) in addition to MF in patients with osteoarthritic knees who underwent medial open wedge high tibial osteotomy (MOWHTO) after an average follow-up of five years.MethodsThe study was designed retrospectively and included patients who underwent MOWHTO due to gonarthrosis, the MF method performed on these patients, and HA + GC treatments applied in addition to MF. Three groups consisting of 79 patients were formed: only HTO (Group 1), HTO + MF (Group 2), and HTO + MF + HA + GC (Group 3). The groups were compared using knee injury and osteoarthritis outcome score (KOOS), visual analog scale (VAS) for pain, and range of motion (ROM). The associations between the degree of correction and function and pain were evaluated. Additionally, the KOOS subparameters were compared between the groups.ResultsThere were significant improvements in the postoperative KOOS and VAS scores in all three groups (p < 0.05). However, the ROM did not improve in Group 1. There was no significant difference in the postoperative KOOS, VAS, or ROM values ​​between Groups 2 and 3, but these values ​​were significantly better in Groups 2 and 3 than in Group 1 (p < 0.05). When the degree of correction increased, there were no significant positive changes in the postoperative KOOS or VAS score in Group 1, unlike in the other two groups (p < 0.05). In corrections of ≥ 10°, while there was no significant difference in the postoperative KOOS or VAS score ​​between Groups 2 and 3, these parameters significantly improved in these two groups compared to Group 1 (p < 0.05). Among the KOOS subparameters, pain and activities of daily living scores ​​were greater in Groups 2 and 3 than in Group 1 (p < 0.05).ConclusionsIn MOWHTO, MF is a sufficient treatment method that improves the patient’s clinical condition without requiring additional treatments such as HA and GC.Level of evidenceIII, retrospective cohort study.

Semi-invasive therapies for pain in knee osteoarthritis: A systematic review and network meta-analysis.

The increasing number of semi-invasive pain therapies in knee osteoarthritis poses challenges in decision-making. This review aimed to simultaneously compare established intra-articular therapies with newer peri-articular therapies and explore effect modifiers. Randomized controlled trials were searched from five electronic databases without date or language restrictions. Study selection and data extraction of reports, retrieved up to May 2024, were performed independently by paired assessors. The primary outcome was 6-month pain score. Nine treatments were included. The effect size (ES) for each treatment, relative to placebo, was estimated using standardized means difference and expressed with 95% confidence intervals (CI). The rigor of results was evaluated with subgroup/sensitivity analyses. A total of 111 studies (14,695 participants) were included, with intra-articular hyaluronic acid having the greatest number of participants. Neuroablation demonstrated the greatest ES (1.08, 95% CI: 0.07, 2.10). While platelet-rich plasma (PRP) ranked second (ES: 0.75, 95% CI: 0.28, 1.22), it was the only intervention demonstrating statistically significant effect at 3, 6, and 12 months. However, this statistical significance was lost in some sensitivity analyses. Larger estimates for biologics and PRP compared with prolotherapy, steroid, and hyaluronic acid injections were consistently observed across different timepoints and in multiple sensitivity analyses. Generally, no statistically significant difference was found between the nine types of therapies. Although there is robust evidence suggesting greater efficacy of PRP, potentially including biologics, over other interventions, future research is needed to identify the phenotype or patient subgroup that would benefit most from PRP.

Association between intra-articular hyaluronic acid injections in delaying total knee arthroplasty and safety evaluation in primary knee osteoarthritis: analysis based on Health Insurance Review and Assessment Service (HIRA) claim database in Republic of Korea

BackgroundThe prevalence of knee osteoarthritis (KOA), a progressive degenerative disease, is gradually increasing, and it is a progressive degenerative disease. In patients with mild-to-moderate KOA, intra-articular hyaluronic acid (IA-HA) has been shown to be an effective non-operative treatment option that can provide significant pain relief and symptom improvement by increasing intra-articular viscoelasticity. This study aimed to evaluate the efficacy of IA-HA injections in delaying total knee arthroplasty (TKA) and the safety of IA-HA according to IA-HA type and combination with intra-articular corticosteroid (IA-CS) using a large health insurance claim database.MethodsFor this retrospective cohort study, the study population included patients aged ≥ 50 years with a first diagnosis of KOA between 2009 and 2014, who underwent TKA by 2020, using the Health Insurance Review and Assessment Service claim database in Republic of Korea. IA-HA injections were categorized as single or multiple injection regimen agents. Cox proportional hazard models estimated hazard ratios (HR) for TKA risk, adjusted for covariates. Logistic regression assessed the occurrence of adverse events after IA-HA administration.ResultsIn all, 36,983 patients were included. Patients who received IA-HA injections had a significantly longer time to TKA compared to those who did not (mean delay of approximately 1 year). The IA-HA group had a significantly lower risk of TKA (HR: 0.61, 95% CI: 0.60–0.62) than non-IA-HA group after adjusting for covariates, which included age, sex, medical history, number of hospital beds, and CS injection. Single injection IA-HA regimen agents showed the longest time to TKA and lowest risk (HR: 0.56, 95% CI: 0.53–0.59). TKA risk decreased with the number of IA-HA cycles. Adverse events occurred in 6.7% of IA-HA cases without CS, with very low incidence of infection. Multiple injection regimen agents (multiple injection regimen 7.0% vs. single injection regimen 3.6%) and concurrent IA-CS use (concurrent IA-CS use 13.9% vs. IA-HA only 6.7%) were associated with higher infection risk.ConclusionIA-HA injections were associated with a significant delay in TKA among patients with KOA. Single-injection regimen agents had the lowest TKA risk. Infection risk increased with multiple injections and concurrent IA-CS use. These findings could suggest the use of IA-HA as an effective non-operative intervention option for managing KOA and delaying TKA. Careful selection of IA-HA type and consideration of concurrent IA-CS use could play a role in delaying the time to TKA and reducing complications.

Combined exosome of adipose-derived mesenchymal stem cell and hyaluronic acid delays early osteoarthritis progression of ovine sheep model: Clinical, radiographic, macroscopic and microscopic evaluation

Background Current treatment of osteoarthritis (OA) mainly focused on treating symptoms. Exosome from Adipose-derived Mesenchymal Stem Cell (Ad-MSC) have been shown to delay degenerative process. This study aimed to investigate the clinical, radiological and histological impact of combined intra-articular (IA) hyaluronic acid (HA) and exosome Ad-MSCs in-vivo using a larger animal model with low-grade OA. Methods Eighteen male Ovies aries sheep underwent total lateral meniscectomy and conventional radiography was performed to confirm low-grade OA after 6 weeks. The sheep were divided into three groups, Group 1 (G1; n=6) received thrice exosome injections, G2 (n=6) received twice HA injection, and G3 (n=6) received both treatments with a 1-week interval after 10 days of meniscectomy. Clinical evaluations were conducted using the Clinical Lameness Score (CLS), radiographic with X-ray using OA score by Innes et al, while macroscopic evaluation by Osteoarthritis Research Society International (OARSI) scores. Results Lameness parameter scored lowest in G3 significantly (2.0±0.0 VS 2.7±0.52 VS 2.7±0.52; p=0.024) at the second month although the overall CLS score did not significantly differ at the 3rd month. The best improvement of conventional total OA radiographic score at the 3rd month compared to all groups (5.2±1.17 vs 6.3±0.82 vs 6.7±1.03; p=0.053). Macroscopic OARSI evaluation showed no difference (p=0.711). Conclusions Combined repeated exosome Ad-MSC and HA IA injection proven to delay OA progression, however longer duration of follow up is required to evaluate its long-term effect.

Predictors of Clinical Benefit with Intra-articular Hyaluronic Acid in Patients with Knee Osteoarthritis - A Narrative Review.

There is conflicting evidence regarding the efficacy of viscosupplementation with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit from this therapy. The purpose of this narrative review is to succinctly summarize the existing data on the predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile most likely to benefit from this therapy. For this narrative review, a PubMed search was conducted in January 2023, with no date limits, to identify publications reporting predictive factors of response to viscosupplementation using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta- analyses, or observational studies written in English. Other relevant references were identified by searching the references of retrieved articles. The disease severity was found to reliably predict response to intra-articular hyaluronic acid injections; patients with less severe disease consistently had a more robust therapeutic response than those with more severe disease. Other clinical variables such as level of baseline pain did not reliably predict response. Body mass index, and possibly age, may also be independent predictors of the response. A review of the existing literature suggests that patients with less severe clinical symptoms and radiological findings, who are younger, and with a lower or normal body mass index are the best candidates for intra-articular hyaluronic acid therapy.

Very-high-molecular-weight vs high-molecular-weight hyaluronic acid injections show long-term sustained benefits in the treatment of osteoarthritis of the knee: a 15-year Indian cohort study

IntroductionLack of confidence in intra-articular hyaluronic acid injections for osteoarthritis (OA) may result from conflicting guidelines and pooling of results for different molecular weight products. ObjectivesThe objectives were to determine responder rates to injections of very-high-molecular-weight hyaluronic acid (VHMW-HA) vs high-molecular-weight hyaluronic acid (HMW-HA) for knee OA and treatment efficacy measured by the interval between follow-up injections. MethodsA retrospective analysis of a 15-year cohort from a single center. Inclusion criteria: adults with Kellgren-Lawrence Grade III or IV knee OA treated with hyaluronic acid injections. Subjects were stratified into 2 groups based on the molecular weight of the hyaluronic acid. Outcome measures were responder rates with improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores of >30% from baseline vs nonresponders; those with a response lasting >6 months after each injection were considered sustained responders. ResultsIn total, 2037 (female 1467 [72.02%] and male 570 [27.98%]) patients were treated. The overall primary responder rate was 73.44% (1496). VHMW-HA had significantly higher primary responders (75.21% vs 70.22%, P = .015) and significantly lower nonresponders (24.79% vs 29.78%, P = .015). As a subset of primary responders, the sustained responders had greater responses with VHMW-HA vs HMW-HA (85.54% vs 67.06%, P < .0001) and lower dropouts (14.46% vs 32.94%, P < .0001). The average interval between the first and the third injections was longer for VHMW-HA vs HMW-HA—5.67 vs 1.95 years (P < .0001). ConclusionsAbout 73.44% of subjects responded to treatment with intra-articular hyaluronic acid. The sustained response was greater in VHMW-HA vs HMW-HA and VHMW-HA has a longer duration of effect than HMW-HA.

Effectiveness of Intra-articular Botulinum Toxin Type A with Hyaluronic Acid Compared to Intra-articular Platelet-rich Plasma with Hyaluronic Acid in Improving Pain and Functional Limitation in Knee Osteoarthritis

Abstract Background: Knee osteoarthritis (KOA) is the most common cause of chronic knee pain causing functional disability and dependency. Multiple interventions have been used in reducing pain and improving functionality. We intend to compare the efficacy of intra-articular platelet-rich plasma (PRP) and hyaluronic acid (HA) with botulinum toxin type A and HA in bilateral Grade 3 and 4 KOA. Methods: Prospective single-blinded randomized controlled trial conducted for 6 months. Among 54 participants, 27 received intra-articular botulinum toxin type A with HA (Group A), and the other 27 received intra-articular PRP with HA (Group B), single session. Pain (Numerical Rating Scale [NRS]) and functional limitation (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were assessed at 2, 4, 12, and 24 weeks postintervention. Effect of weight and physiotherapy on NRS and WOMAC score were assessed. P &lt;0.05 was considered statistically significant. Data were analyzed by statistical software R version 4.2.3. Results: Fifty-four participants were enrolled. There was no loss to follow-ups. Except for age (P &lt; 0.001) and mean height (P = 0.013), other demographic data were insignificant. Preprocedural NRS was significantly high in Group A (P = 0.04). Overall NRS postprocedure was significantly lesser in Group B, P &lt; 0.001. The mean WOMAC score postprocedure was significantly low in Group B, P &lt; 0.001. Group B had increased heart rate which was statistically significant (P = 0.051). The mean reduction in WOMAC score was observed with regular physiotherapy in Group B (P = 0.023). Reduction in weight was directly proportional to reduction in NRS (P = 0.015). Conclusion: Intra-articular PRP with HA, single session, is effective in improving pain, functionality, and safe in Grade 3 and 4 KOA.

The Effect of Intra-Articular Injections of Hyaluronic Acid for the Treatment of Trapezio-Metacarpal Joint Osteoarthritis.

Osteoarthritis of the basal thumb joint is a debilitating disease with a high prevalence. Among pharmacological treatments, intra-articular injections of hyaluronic acid have been clinically applied. This study aimed to investigate the effectiveness and safety of intra-articular injections of hyaluronic acid for the treatment of trapezio-metacarpal joint osteoarthritis (TMOA), over a one-year period. Patients with TMOA were enrolled and treated with five consecutive intra-articular injections of hyaluronic acid (20 mg/2 mL, 500-750 KDa, HyalganBio) at weekly intervals. Primary outcomes were pain during different activities (changes in numerical rating scale) and function (pinch and grip strength), and secondary outcomes were safety (adverse events) and patient-reported outcomes (quick-DASH and SF-12). The outcomes were evaluated at baseline and 1-, 3-, 6-, and 12- months after the last injection. A total of 29 patients were included. All participants completed the five injective sessions and the first follow-up. A total of 15 patients completed the study. During the follow-up period, intra-articular injections of hyaluronic acid have significantly reduced spontaneous and provoked pain and improved disability. No severe systemic adverse events were reported. At a follow-up of up to 12 months, patients with TMOA treated with intra-articular hyaluronic acid injections reported improvements in pain relief and quality of life.

Can Hyaluronic Acid Combined with Chondroitin Sulfate in Viscosupplementation of Knee Osteoarthritis Improve Pain Symptoms and Mobility?

The objective of the present study was to assess the effect of intra-articular Hyaluronic acid (HA) and Chondroitin sulfate (CS) supplementation (Hialurom® Hondro (HH)) on pain symptoms and joint mobility. In total, 60 mg/mL sodium hyaluronate and 90 mg/mL CS were administered to 21 patients (17 females and 4 males) respecting the in-force requirements, excluding patients with some specific comorbidities. In addition to the clinical study (where the pain intensity (severity) and joint mobility were assessed), rheological characterization was conducted evaluating the following parameters: elastic modulus (G'), loss modulus (G″) oscillatory frequency (fc) at 0.5 Hz and 2.5 Hz, crossover frequency (fc), relaxation time (λ) where it was noticed that the addition of chondroitin sulfate (CS) to sodium hyaluronate (SH) significantly enhances and improves the viscoelastic properties, particularly at higher shear frequencies. A significant decrease in pain intensity felt by the subjects was found, from 7.48 (according to Wong-Baker scale)-pain close to 8 (the patient is unable to perform most activities), to more reduced values of 5.86-at 6 weeks after injection, 4.81-at 3 months after injection, and 5.24-at 6 months after injection, improvements in symptoms was fast and durable. Data related to the evolution of joint mobility show that at 6 weeks after injection, the mobility of joints increased by 17.8% and at 6 months by 35.61%. No serious adverse events were reported with undesired effects so that they would impose additional measures. Better resistance to enzymatic degradation and free radicals could be expected from the synergic combination of sodium hyaluronate and chondroitin sodium sulfate, this having a special importance for the patients, granting them the ability to perform more ample movements and reducing dependency on attendants, thus increasing quality of life.

Costs and Timing of Surgery in the Management of Meniscal Tears.

Treatment strategies for meniscal tears range from nonoperative management to surgical intervention. However, national trends in cost-related outcomes and patient factors related to the failure of nonoperative management remain poorly understood. To describe the costs associated with nonoperative versus operative management of meniscal tears in the 2 years after diagnosis and examine the relationship between patient characteristics and timing of surgery. Cross-sectional study; Level of evidence, 3. This study was conducted using the MarketScan databases. Patients diagnosed with a meniscal tear without concomitant knee osteoarthritis between January 1 and December 31, 2017, were included. The primary outcome was the total cost of meniscal tear-related procedures-including insurance deductibles, coinsurance, and net insurance payments-in the 2 years after diagnosis. Procedures included were as follows: (1) surgery-including meniscectomy or meniscal repair; (2) physical therapy; (3) medication-including nonsteroidal anti-inflammatories, opioids, and acetaminophen; (4) intra-articular injections-including professional fee, hyaluronic acid, and corticosteroids; (5) imaging; and (6) clinic visits to orthopaedic specialists. Patients were grouped as having undergone early surgery (ES) (≤3 months of diagnosis), late surgery (LS) (>3 months after diagnosis), or no surgery (NS). Multivariate logistic regression was performed to determine the likelihood of undergoing surgery early and failing nonoperative treatment. The study population included 29,924 patients with a mean age of 43.9 ± 12.9 years (ES: n = 9507 (31.8%); LS: n = 2021 (6.8%); NS: n = 18,396 (61.5%)). Complex (36.6%) and medial (58.8%) meniscal tears were the most common type and location of injuries, respectively. The mean cost of management per patient was $3835 ± $4795. Costs were lower in the NS group ($1905 ± $3175) compared with the ES group ($6759 ± $5155), while the highest costs were observed in the LS group ($7649 ± $5913) (P < .001). Patients who were men, >40 years, and with a bucket-handle or lateral meniscal tear were more likely to undergo surgery early. Patients who were men, <30 years, and with a complex tear or tear to the lateral meniscus were more likely to fail nonoperative management. Nonoperative management had the lowest cost burden and should be recommended for patients with appropriate indications. However, if surgery is necessary, it should be performed earlier.

Time to Total Knee Arthroplasty (TKA) Post Intra-Articular Injection.

Background: Disease-modifying treatments are not currently developed to target the underlying causes of knee osteoarthritis (KOA). Corticosteroids (CS), hyaluronic acid (HA), and platelet-rich plasma (PRP) intra-articular (IA) injections are commonly used for patients that do not respond to non-pharmacological treatments, oral nonsteroidal anti-inflammatory, or pain medications to address solely KOA symptoms. Utilizing TKA as an endpoint in the KOA disease progression provides a basis to determine efficacy of this treatment pathway. The primary objective is to evaluate a large national database to determine the time between first injection and total knee arthroplasty in patients solely administered intra-articular IA, CS, and HA. Methods: A retrospective query was performed on a national, all-payer claims database (PearlDiver, Colorado Springs, CO, USA), a composite of over 160 million Health Insurance Portability and Accountability Act compliant orthopedic records across all states and territories of the United States spanning 2016 to 2022. The database was queried to produce three distinct cohorts for analysis (PRP, HA, and CS). A 4:1 case match was conducted to compare cohorts receiving a subsequent TKA. Kaplan-Meier survival analysis analyzed the TKA-free survival of patients within each group at 6 months and 1 to 4 years. The log-rank test was performed for comparisons between survival cohorts. Results: The PRP cohort had a total population of 3240 patients, of which 71 (2.2%) received a subsequent TKA. The corticosteroid cohort had a total population of 1,382,572, of which 81,271 (5.9%) received a subsequent TKA. The HA cohort had a total population of 164,000, of which 13,044 (8.0%) received a subsequent TKA. Due to the low population within the PRP group, this group was excluded from comparison. The mean time to TKA from first injection in the HA group was 377.8 days, while in the corticosteroid group it was 370.0 days. The proportions of TKA-free survival for CS and HA when compared at 4 years post-injection was similar between groups (p = 0.05). Discussion and Conclusion: Patients that received only IA-corticosteroids or IA-hyaluronic acid had a similar length of time between the first injection and the total knee arthroplasty associated with the injected joint. This evidence provides information for clinicians and patients alike when contemplating these non-surgical injection modalities for KOA. The similarity observed between these treatments supports the need for future research to determine whether there is any potential for reduction in healthcare costs for KOA treatment prior to TKA.

Exploring the Superior Efficacy of Hyaluronic Acid and Platelet-Rich Plasma Co-Administration Over Hyaluronic Acid Alone in Pain Reduction and Functional Status Improvement of Knee Osteoarthritis Patients

Objective: This study aimed to determine whether concurrent injection of hyaluronic acid (HA) with platelet-rich plasma (PRP) would enhance therapeutic effectiveness compared to HA alone in the management of knee osteoarthritis (OA) over a 12-month follow-up. Methodology: A prospective, comparative study was conducted in department of orthopedic Nawaz Sharif Medical College / Aziz Bhatti Shahed Hospital Gujrat from Jan 2023 To Dec 2023 on 100 patients with knee OA (Kellgren-Lawrence grades I-III). The patients were divided into two groups: Group 1, consisting of 50 patients, received intra-articular HA injections, while Group 2, comprising the remaining 50 patients, received a combination of HA and PRP. Pain and functional outcomes were assessed using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at baseline, and at 2, 6, and 12-months post-injection. Results: Assessments at baseline, 2 months, 6 months, and 12 months post-injection revealed significant improvement in both groups compared to baseline. However, patients in Group 2 (HA+PRP) showed significantly greater improvement than those in Group 1 (HA alone), with WOMAC scores at 2-, 6-, and 12-months yielding p-values of 0.001*, 0.001*, and 0.000*, respectively. Conclusions: The study concluded that the combination of PRP and HA is more effective than HA alone in reducing pain and improving joint function in patients with knee OA. The findings suggest that PRP+HA offers superior benefits for managing knee osteoarthritis compared to HA alone.

Improved Pain and Function With Triamcinolone Acetonide Extended-Release and Cryoneurolysis for Knee Osteoarthritis: Use of a New Real-World Registry

BackgroundKnee osteoarthritis (OA) affects 19% of American adults aged more than 45 years and costs $27+ billion annually. A wide range of nonoperative treatment options are available. This study compared 6 treatments: cryoneurolysis with deep genicular nerve block (Cryo-Deep/Both), cryoneurolysis with superficial nerve block (Cryo-Superficial), intra-articular hyaluronic acid (IA-HA) injections, nonsteroidal anti-inflammatory drug injections (IA-NSAIDs), IA-corticosteroids (IA-CS) injections, or IA-triamcinolone extended release (IA-TA-ER) injections over 4 months for: (1) pain severity and analgesic use; and (2) physical function (from Knee Injury and Osteoarthritis Outcome Score for Joint Replacement). MethodsPatients who had unilateral knee OA and received nonoperative intervention were enrolled in the Innovations in Genicular Outcomes Research registry, a novel, multicenter real-world registry, between September 2021 and February 2024. A total of 480 patients were enrolled. Both pain and functional outcomes were assessed at baseline, weekly, and monthly, which were analyzed by overall trend, magnitude changes pretreatment to post-treatment, and distribution-based minimally clinically important difference (MCID) score. Multivariate linear regressions with adjustments for 7 confounding factors were used to compare follow-up outcomes among 6 treatment groups. ResultsUse of IA-TA-ER injections was associated with the lowest pain, greatest pain reduction, and highest prevalence of patients achieving MCID relative to other treatments (P < .001). Deep/Both-Cryo and IA-CS were associated with a higher prevalence of achieving MCID than IA-HA, IA-NSAIDs, and Cryo-Superficial (P ≤ .001). Use of IA-TA-ER was also associated with the greatest functional score, improvement from baseline, and highest prevalence of patients achieving MCID than other treatments (P ≤ .003). ConclusionsThe IA-TA-ER appears to outperform other treatments in terms of pain relief and functional improvement for up to 4 months following treatment. In addition, outcomes in the novel cryoneurolysis and conventional IA-CS were similar to one another and better than those in IA-HA and IA-NSAIDs.

Comparison of the short-term effect of intra-articular hyaluronic acid and platelet-rich plasma injections in knee osteoarthritis: a randomized clinical trial.

Osteoarthritis (OA) is one of the most common degenerative joint diseases which involved all joints. It is very important to choose a treatment method with high efficiency to reduce the pain and disability of patients and also to improve their quality of life. The current study aimed to investigate the therapeutic effects of intra-articular injection of PRP and hyaluronic acid (HA) in the knee of people with knee osteoarthritis (KOA). In this randomized clinical trial study, 90 patients with KOA were randomly divided into two groups of intra-articular HA and PRP. The patients of the two groups were followed up for five months and different outcomes were recorded. The McMaster index (WOMAC) evaluated all patients at rest and during movements. Measurements were taken at the beginning and after the third month of follow-up. Three month after the last injection (5th month) and after adjusting of baseline value using analysis of covariance, the mean of knee pain, stiffness, physical function and finally total score in the PRP group, was significantly lower than the HA group. Regarding the Osteoarthritis grade, the mean of knee pain, Stiffness, Physical function and finally total score in the PRP group was significantly lower than the HA group in all Osteoarthritis grades. Also, there were no complications in the studied groups. The results of the current study showed that pain and stiffness reduction as well as physical function of the knee joint in the PRP group was better than in the HA group.

Combined exosome of adipose-derived mesenchymal stem cell and hyaluronic acid delays early osteoarthritis progression of ovine sheep model: Clinical, radiographic and macroscopic evaluation

Background Current treatment of osteoarthritis (OA) mainly focused on treating symptoms. Exosome from Adipose-derived Mesenchymal Stem Cell (Ad-MSC) have been shown to delay degenerative process. This study aimed to investigate the clinical, radiological and histological impact of combined intra-articular (IA) hyaluronic acid (HA) and exosome Ad-MSCs in-vivo using a larger animal model with low-grade OA. Methods Eighteen male Ovies aries sheep underwent total lateral meniscectomy and conventional radiography was performed to confirm low-grade OA after 6 weeks. The sheep were divided into three groups, Group 1 (G1; n=6) received thrice exosome injections, G2 (n=6) received twice HA injection, and G3 (n=6) received both treatments with a 1-week interval after 10 days of meniscectomy. Clinical evaluations were conducted using the Clinical Lameness Score (CLS), radiographic with X-ray using OA score by Innes et al, while macroscopic evaluation by Osteoarthritis Research Society International (OARSI) scores. Results Lameness parameter scored lowest in G3 significantly (2.0±0.0 VS 2.7±0.52 VS 2.7±0.52; p=0.024) at the second month although the overall CLS score did not significantly differ at the 3rd month. The best improvement of conventional total OA radiographic score at the 3rd month compared to all groups (5.2±1.17 vs 6.3±0.82 vs 6.7±1.03; p=0.053). Macroscopic OARSI evaluation showed no difference (p=0.711). Conclusions Combined repeated exosome Ad-MSC and HA IA injection proven to delay OA progression, however longer duration of follow up is required to evaluate its long-term effect.

Evidence of the clinical effect of commonly used intra‐articular treatments of equine osteoarthritis

SummaryBackgroundOsteoarthritis (OA) is a common disease in equine patients that causes joint pain and loss of function. The aetiology of OA is assumed to be multifactorial. A range of medical treatments are on the market for symptomatic treatment of OA in equine patients, both biological and conventional options. Today, no true disease‐modifying osteoarthritis drug (DMOAD) is available.ObjectiveTo summarise the current evidence of the clinical effect of commonly used intra‐articular treatments of equine OA, specifically the use of intra‐articular glucocorticosteroids (IA‐GCs), intra‐articular hyaluronic acid (IA‐HA), intra‐articular platelet‐rich plasma/autologous‐conditioned plasma (IA‐PRP), intra‐articular interleukin‐1 receptor antagonist protein/autologous‐conditioned serum (IA‐IRAP) and intra‐articular mesenchymal stem cells (IA‐MSCs).Study designSystematic review.MethodsUsing the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines, a comprehensive search identified 22 clinical studies where horses with OA, naturally occurring or induced, were treated with one of the mentioned intra‐articular treatments. The studies were reviewed to collect all in vivo studies with clinical follow‐up on horses with OA.ResultsIA‐GCs seem to have a beneficial short‐term clinical outcome. Treatment with IA‐HA shows varying clinical results and provides uncertain evidence for a beneficial clinical effect. IA‐PRP shows overall promising clinical results for a significant improvement. IA‐IRAP shows promising significant clinical effect, but most of the studies lack a control group for comparison. IA‐MSCs show varying clinical results, but a majority of the included studies show evidence for a significant improvement in clinical effect.ConclusionTo provide stronger evidence of the clinical effect of the five chosen treatments, further blinded, randomised and placebo‐controlled studies are needed.