Hyaluronic Acid For Knee Osteoarthritis Research Articles

A comparison of intra-articular hyaluronic acid and platelet-rich plasma for knee osteoarthritis: a systematic review.

Knee osteoarthritis (KOA), the most common chronic degenerative condition in an older population, accounts for many disabilities around the world. One of the most popular treatments is intra-articular injection of hyaluronic acid (HA) and platelet-rich plasma (PRP). Prior studies have found that both HA and PRP had a therapeutic effect on KOA. This study aims to perform a systematic review regarding whether PRP is superior to HA for KOA. We conducted a comprehensive literature search using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for prospective randomized control trials (pRCTs) in three international databases PubMed, Google Scholar, and ScienceDirect from 2019-2022. Two researchers independently searched the reviews, extracted, and cross-checked the data. The disparity when choosing the literature was resolved by discussion. The modified Jadad was scale used to assess the quality of the included studies. Cochrane risk of bias 2 tool (RoB-2) was used for determininzg risk of bias. Twenty three studies were eligible for inclusion. Four pRCT with the highest Jadad score were selected as best evidence. Risk of bias assesment concluded two studies having a low risk of bias, one is high risk of bias, and the other possesses some concerns.. Three studies found no difference in patient-reported outcomes between PRP and HA group and one study concluded that PRP is more effective than HA in treating KOA. Intra-articular injections of PRP and HA are effective interventions for KOA. However, there is not enough evidence of PRP superiority over HA.

Evaluation of single and multiple hyaluronic acid injections at different concentrations with high molecular weight in the treatment of knee osteoarthritis

BackgroundKnee osteoarthritis is severe progressive and most commonly diagnosed articular disease and its incidence is increasing around the world depending on age. This pathologic condition which limits daily activity of patients can be characterized by degeneration of cartilage and inflammation. Although non-steroidal anti-inflammatory (NSAII) agents and other analgesics are routinely used treatment options, the potential effects of intraarticular injections including hyaluronic acid (HA) have also been demonstrated by various studies. However, few studies compare the efficacy of a single high molecular weight (HMW) high dose and a triple HMW low dose. This study aimed to compare the efficacy of single high molecular weight (HMW) high dose (2 mL / 60 mg) and triple HMW low dose (2 mL /30 mg) intra-articular injection of HA in knee osteoarthritis (OA) patients by evaluating function and pain parameters during 12 months.MethodsThis is a single-center, retrospective clinical study that included and involved 128 patients. Group I (n=64) patients received triple 30 mg HA injections (SEMICAL®) with one-week intervals, while Group II (n=64) patients received a single 60 mg HA injection (SEMICAL®). Lequesne Index, WOMAC and VAS scores were recorded to assess pain and function during a 12-month period.ResultsThere was no significant difference in characteristics of patient demographics. Our finding indicate that WOMAC, VAS score, and Lequesne Index values during follow-up visits exhibited a decrease, signifying improvement in the clinical condition. Notably, scores were significantly more favorable with the 30 mg of HA injection compared to the 60 mg of HA injection.ConclusionThis study suggests that the triple low-dose injection of HMW HA is more effective in improving WOMAC, VAS scores and Lequesne Index values than a single high-dose injection.

Efficacy of Intra-Articular Injection of a Blend of Cross-Linked- Linear Hyaluronic Acid in Knee Osteoarthritis

Efficacy of Intra-Articular Injection of a Blend of Cross-Linked- Linear Hyaluronic Acid in Knee Osteoarthritis

Multiple Injections of Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Current Evidence in Randomized Controlled Trials.

In recent years, various clinical trials have focused on treating knee osteoarthritis (KOA) with multiple injections of platelet-rich plasma (PRP). However, compared with the multiple hyaluronic acid (m-HA) injections, the clinical efficacy of multiple PRP (m-PRP) injections for KOA still remains controversial among these studies. Therefore, we aimed to compare the clinical effectiveness of m-PRP injections with m-HA injections in the treatment of KOA in this systematic review. Relevant clinical trials were searched via bibliographic databases, including Medline, PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, to compare the m-PRP and m-HA injections in the treatment of KOA. Finally, fourteen randomized controlled trials, including 1512 patients, showed the postoperative VAS, WOMAC, IKDC, or EQ-VAS scores and were enrolled in this systematic review. Compared with the group of intra-articular m-HA injections, the group of intra-articular m-PRP injections was lower in the VAS scores at 3-month (WMD = -0.25; 95%CI, -0.40 to -0.10, p = 0.0009) and 12-month (WMD = -0.64; 95%CI, -0.79 to -0.49, p < 0.00001) follow-ups. In addition, the group of intra-articular m-PRP injections was also lower in the WOMAC scores at 1-month (WMD = -1.23; 95%CI, -2.17 to -0.29, p = 0.01), 3-month (WMD = -5.34; 95%CI, -10.41 to -0.27, p = 0.04), 6-month (WMD = -11.02; 95%CI, -18.09 to -3.95, p = 0.002), and 12-month (WMD = -7.69; 95%CI, -12.86 to -2.52, p = 0.004) follow-ups. Furthermore, compared with the group of intra-articular m-HA injections, the group of intra-articular m-PRP injections was higher in the IKDC scores at 3-month (WMD = 7.45; 95%CI, 2.50 to 12.40, p = 0.003) and 6-month (WMD = 5.06; 95%CI, 1.94 to 8.18, p = 0.001) follow-ups. However, the long-term adverse side of m-PRP injections for KOA still needs more large-scale trials and long-term follow-ups.

Restoring Study PRGF: a randomized clinical trial on plasma rich in growth factors for knee osteoarthritis

BackgroundA randomized clinical trial assessing plasma rich in growth factors (PRGF) versus hyaluronic acid for knee osteoarthritis was published in 2012 (sponsor trial ID BTI-01-EC/07/ART). Evidence of misreporting was discovered following access to unpublished materials. In accordance with the principles of the Restoring Invisible and Abandoned Trials (RIAT) initiative, we sought to re-analyse Study PRGF based on the unpublished trial materials.MethodsReanalysis was made possible primarily based on two unpublished study documents (original trial protocol and final report) obtained from the authors of the original publication. A call to action, calling on the authors to correct the original publication, was publicly issued. The involved ethics committee was repeatedly approached and extensive discussion with the authors ensued. After no agreement to correct the paper was reached, we embarked on this restoration. Reanalysis was focused on providing updated analyses for efficacy and safety.ResultsThe efficacy of PRGF was not statistically different from hyaluronic acid for any prespecified primary or secondary efficacy outcomes. For the primary endpoint, the percent of patients on PRGF compared to hyaluronic acid with a decrease >40% in WOMAC pain subscale score was 5.4% higher; 95% confidence interval (CI) −10.4% to 21.3%; p = 0.505. This differs from the original publication that reported a non-prespecified primary endpoint (decrease >50% in WOMAC pain subscale score) which was 14.1% higher; 95% CI 0.5 to 27.6%; p=0.044. Furthermore, in contrast to the article statement that all the adverse events disappeared in 48 h, at least two patients in the hyaluronic arm and five patients in the PRGF arm reported persistent adverse events. Inadequate disclosure of conflicts of interest in the original publication was also noted.ConclusionsThis reanalysis of Study PRGF found no clinically or statistically significant benefit from PRGF compared to hyaluronic acid. The restoration of Study PRGF shows the urgency of important changes to trial reporting and oversight practices. In the future, timely access to all clinical trial documents is needed to minimize the risk of reporting bias. Similarly, ethics committees should be ready to intervene whenever a case of potential misconduct arises.Trial registrationThis is a RIAT project, whose original trial was approved and registered on 19 December 2007 by the Ethics Committee of the Basque Country, Spain, as BTI-01-EC/07/ART.

Inyección intraarticular única de ácido hialurónico en la gonartrosis sintomática: estudio comparativo de la eficacia de dos presentaciones y cambio de protocolo.

Introduction: Vicosupplementation with hyaluronic acid in knee osteoarthritis has proven to be a safe and effective treatment. Its effectiveness is maintained for at least 6 months. Few studies have compared the efficacy of two single injection products at 12 months. Objective: To evaluate the efficacy results in patients infiltrated with two single injection hyaluronic acid : Hyalone® (H) and Adant One® (A), at 12 months. Material and methods: A retrospective observational study has been designed on a cohort of patients with knee osteoarthritis. They were treated by intra-articular knee viscosupplementation with two types of single injection hyaluronic acid. Its efficacy was evaluated according to the WOMAC scale and the VAS at 6 and 12 months. Results: 86 patients were treated with single doses of A and 67 with H. A significant improvement was found in the WOMAC assessment at 6 months with A (p = 0.035), while at 12 months the result no longer showed statistical significance (p = 0.184). With H at 12 months the improvement in the WOMAC values continued to be favorable (p = 0.039). Regarding pain control, an improvement in the VAS was observed, which was significant only in the case of H at 12 months (p = 0.020). Conclusions: A single H injection at 12 months was more effective for pain control and improved functionality in patients with knee osteoarthritis compared to A. It is possible to make viscosupplementation protocols for knee osteoarthritis with hyaluronic acid at annual intervals using H.

Public Interest in Hyaluronic Acid Injections for Knee Osteoarthritis in the United States and Europe: An International Google Trends Analysis.

Hyaluronic acid injections remain a common nonsurgical alternative for the treatment of knee osteoarthritis despite limited clinical evidence and varying global recommendations regarding its use. We used the Google Trends tool to provide a quantitative analysis of public interest in hyaluronic acid injections for knee osteoarthritis in the United States and Europe. We customized Google Trends parameters to obtain search data from January 2009 to December 2019 in both the United States and Europe. Combinations of "arthritis", "osteoarthritis", "hyaluronic acid", "knee arthritis", "knee osteoarthritis", and "knee injection" were entered into the Google Trends tool, and trend analyses were performed. The models generated to describe public interest in hyaluronic acid for knee injections in both the United States and Europe showed increased Google queries as time progressed (P < .001). The United States growth model displayed linear growth (r2= 0.90) while the European growth model displayed exponential growth (r2= 0.90). Our results indicate a significant increase in Google queries related to hyaluronic acid injections for knee osteoarthritis since 2009 in both the United States and Europe. Our models suggest that despite mixed evidence supporting its use, orthopedic surgeons should expect continued public interest in hyaluronic acid for knee osteoarthritis. The results of our study may help to prepare surgeons for patient inquiries, inform the creation of evidence-based shared decision-making tools, and direct future research.

Assessment of the effectiveness and satisfaction of platelet-rich plasma compared with hyaluronic acid in knee osteoarthritis at minimum 7-year follow-up: A post hoc analysis of a randomized controlled trial.

Background: Knee osteoarthritis (KOA) can be effectively treated conservatively using platelet-rich plasma (PRP) injections into the affected joints. While the short-term therapeutic clinical benefits were well documented, the mid-term results remain undetermined. To clarify its efficacy, the mid-term clinical outcomes of intra-articular injections of either PRP or hyaluronic acid (HA) in KOA were compared. Methods: One hundred patients who complied with the inclusion criteria were randomized to undergo once a week 3weeks, intra-articular injections of either PRP or HA. Patients were evaluated before the injection, at 3, 6, and a mean of 78.9 months of follow-up. Eighty-five patients reached the final evaluation. Data on survival, re-intervention, pain, function, imaging, and satisfaction were collected and analyzed. Results: With surgery for any reason as the endpoint, the cumulative survival rate of the PRP group was 90%, while that of the HA group was 74%. There was a significant difference between the two groups in the total re-intervention rate (56.7% vs 16.2%, p < 0.05). The comparative analyses showed significant intergroup differences in the visual analog scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) (p < 0.01, p < 0.05, respectively) at the final follow-up. And base on the regression analyses, the type of treatment, age, and Kellgren-Lawrence (K-L) grade served as statistically an independent determinants of VAS (p < 0.001, p = 0.034, p < 0.001, respectively). Likewise, those variables independently determined WOMAC in our study. However, no difference was observed in the imaging evaluation, containing the K-L grade and Cartilage Lesion Score, between the two groups (p > 0.05). Besides, the satisfaction treated by the PRP was 78.6%, with a superiority compared with HA (55.8%, p < 0.05), and no complications were noted in the whole treatment process among patients who participated. Conclusion: PRP was more effective than HA in survival and re-intervention rates, VAS, and WOMAC, although there were no significant differences in the imaging evaluation between the two groups. Furthermore, patients treated with PRP were associated with higher satisfaction compared with HA.

An Open-Labeled Randomized Prospective Multi-center Study to Evaluate the Efficacy and Safety of Intra-articular Injection of OSSINEXT™, an Autologous Growth Factor Concentrate (AGFC) Compared to Hyaluronic Acid (HA) in Knee Osteoarthritis.

Osteoarthritis (OA) is known as degenerative arthritis and is the second most common rheumatologic problem with a prevalence of 22%-39% in India. Knee OA (KOA) is a major cause of mobility impairment, particularly among females. Non-surgical treatment options for KOA include intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA). Most commercially available PRP preparation kits do not remove RBCs and WBCs which are detrimental to the healing effects. Wockhardt Regenerative Pvt. Ltd., Mumbai, India has developed a kit known as Ossinext™ which has an advantage over traditional PRP in that it eliminates RBCs and WBCs. This study was conducted to evaluate the effectiveness and safety of intra-articular injection of Wockhardt's Ossinext™ an autologous growth factor concentrate (AGFC) versus HA in KOA. Male and female patients in the age group between 30 and 75 years with confirmed KOA on radiological assessment with Grades I-III on the Kellgren-Lawrence Grading Scale and with visual analog scale (VAS) pain score of 4 or more (on the numeric rating scale) in spite of taking non-steroidal anti-inflammatory drugs (NSAIDs) since past 2 weeks were considered for study participation. This was an open-labeled study and eligible patients were randomly allocated to AGFC or HA in a 1:1 fashion. Three intra-articular injections were given in the affected knee joint, i.e. at baseline, month 1, and month 2 visits. Patients were evaluated at regular intervals, i.e. at months 5, 8, and 11 for primary and secondary endpoints. The primary efficacy endpoint for this study was change from baseline in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores at month 11 whereas the secondary efficacy endpoints were change from baseline of VAS pain scale at months 1, 2, 5, 8, and 11 as well as change from baseline of WOMAC, KOOS (Knee and Osteoarthritis Outcome System), and IKDC (International Knee Documentation Committee) scale at month 5, 8, and 11. For analysis a mixed model for repeated measures was used. Out of the 100 patients who were enrolled, 50 patients each were randomized to AGFC and HA arm. The results were analyzed from 99 patients (49 for AGFC and 50 for HA) who met the criteria for the modified intent to treat (mITT) population. At month 11 on the WOMAC scale, there was greater improvement seen with Ossinext™ compared to HA group which was also statistically significant with p-value of 0.0332. Within the group, there was statistically significant improvement before and after treatment in all scales, i.e.WOMAC, KOOS, IKDC, and VAS at all time points, i.e. months 5, 8, and 11 with a p-value as low as <0.0001. Within the group, the VAS score showed statistically significant improvement even at months 1 and 2 as well. A total of 24 patients reported 37 adverse events (AEs) during the study, most common being pain, pyrexia and swelling but none of the AEs reported during the study were considered as severe in intensity. There were no safety concerns reported. In conclusion, greater and statistically significant improvement was seen with Ossinext™ in WOMAC scores at month 11 compared to HA. Ossinext™ also showed marked statistically significant improvement from before treatment to after treatment in the WOMAC, KOOS, IKDC, and VAS scales used for the assessment of KOA with a p-value as low as <0.0001. Ossinext™ was also safe and well-tolerated.

Are leukocyte-poor or multiple injections of platelet-rich plasma more effective than hyaluronic acid for knee osteoarthritis? A systematic review and meta-analysis of randomized controlled trials.

Platelet-rich plasma (PRP) has gained popularity as a treatment option for knee osteoarthritis; however, its efficacy remains controversial. The optimal leukocyte concentration and number of injections have not been well investigated. This study was, therefore, designed to provide clinical evidence on the leukocyte concentration and number of intra-articular injections of PRP via a meta-analysis of randomized controlled trials (RCTs). The MEDLINE, Embase, Cochrane Library, CINAHL, and Scopus databases were searched and RCTs comparing PRP and hyaluronic acid (HA) for treating knee osteoarthritis were included. Clinical outcomes, including visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and adverse reactions, were evaluated. A total of 138 studies were screened, of which 21 level 1 RCTs (2086 knees; 1077 PRP and 1009 HA) were included. PRPs showed significant improvement in pain according to the VAS score compared to HA at 6 and 12months, regardless of leukocyte concentration. Both single and multiple injections of PRP improved pain better than HA at 12months. Regarding function, both single and multiple injections of leukocyte-poor PRP and leukocyte-rich PRP led to significantly better improvement in total WOMAC score compared with HA at 6months. There was no significant difference in procedure-related knee pain or swelling between the PRP and HA groups. Leukocyte-rich PRP had a significantly higher odds ratio for procedure-related knee pain or swelling compared to HA (odds ratio, 3.3 [95% confidence interval, 1.1-10.2], P = .037). Based on evidence from Level 1 studies, intra-articular injection of PRP improves pain and function in patients with knee osteoarthritis for up to 12months and is superior to HA, regardless of leukocyte concentration or number of injections. The findings of this study support the routine clinical use of intra-articular injections of PRP for the treatment of knee osteoarthritis, regardless of the type and frequency of PRP injection. Meta-analysis of level I studies.

Efficacy and clinical outcomes of intra-articular injection of platelet-rich plasma versus hyaluronic acid for knee osteoarthritis

Efficacy and clinical outcomes of intra-articular injection of platelet-rich plasma versus hyaluronic acid for knee osteoarthritis

Evaluation of the effectiveness of intra-articular administration of highly purified hyaluronic acid in knee osteoarthritis in real clinical practice

Knee osteoarthritis (kOA) is a common cause of turning for medical advice, associated with chronic pain and disability. One of the methods of OA treatment is the local administration of hyaluronic acid (HA) drugs.Objective: to evaluate the effectiveness of intra-articular (IA) administration of highly purified HA (Armaviskon Plus) in kOA.Patients and methods. The study group consisted of 58 patients (74.1% women and 25.9% men, aged 59.5±11.8 years) with kOA, experiencing moderate/severe pain (≥40 mm on a visual analogue scale, VAS). All patients received IA injection of HA Armaviskon Plus (2 ml of a 1.5% solution), 2 injections with an interval of 7 days. The effectiveness criterion was the dynamics of pain at rest and during movement (VAS 0-100 mm) and the function of the knee joint according to a numerical rating scale (NRS 0-100 points) 2 weeks, 1 and 3 months after administration of therapy.Results and discussion. During the treatment, there was a significant improvement in all indicators. The average severity of pain during movement at baseline, after 2 weeks, 1 and 3 months was 50 [40; 60], 30 [20; 40], 15 [0; 30], 20 [0; 30] mm (p&lt;0.001), at rest 20 [10; 40], 5 [0; 20], 0 [0; 20], 10 [0; 20] mm (p&lt;0.05) by VAS. The average values of functional indicators were 40 [10; 60], 10 [0; 40], 20 [0; 40], 10 [10; 30] scores according to the NRS. A decrease in non-steroidal anti-inflammatory drugs demand was recorded: 67.1% of patients were initially taking them, after 3 months – 36.1% (p&lt;0.001). No serious adverse reactions were noted.Conclusion. IA administration of HA is an effective and safe method for the treatment of kOA. Armaviskon Plus, a highly purified high-molecular- weight HA drug, has shown good results in pain reduction and improvement of function in knee OA as well as a favorable safety profile, which makes it possible to recommend its use in real clinical practice.

Hyaluronic acid in knee osteoarthritis - effectiveness and efficiency

Hyaluronic acid in knee osteoarthritis - effectiveness and efficiency

Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis

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

Does hyaluronic acid injection prevent the progression of knee Osteoarthritis ?

Purpose: Intra-articular injection of hyaluronic acid (HA) is performed as a conservative treatment for knee osteoarthritis (OA). HA has diverse pharmacological actions. In addition to increased lubrication of joint surfaces, its actions have been reported to include inhibition of the release of inflammatory cytokines and promotion of endogenous HA production. While many reports have suggested that injection of HA is clinically effective for knee OA, the actual improvement only seems to be modest. It has also been reported that injection of HA did not prevent the progression of knee OA, but rather promoted it. Thus, there are many unanswered questions about intra-articular HA therapy. The purpose of this study is imaging evaluation of patients who received long-term treatment with intra-articular HA for knee OA was conducted. Methods: This study was conducted in accordance with all applicable requirements of our university (including IRB approval). The subjects were 42 patients/64 knees (male: 17, female: 25) who received long-term intra-articular injection of HA for knee OA at the outpatient clinic of our university. Their mean age was 74.0 years, and the mean observation period was 4 years and 7 months. Knee radiographs were assessed by the Kellgren-Lawrence (K-L) classification, and the joint space was measured on frontal and lateral views obtained with the patient in the standing semiflexion position. In addition, the height, body weight, body mass index (BMI), frequency of HA injections, and total dose of HA were evaluated. Radiographic disease progression was defined as an annual increase of at least 1 grade in the K-L score or a decrease of > 0.2 mm in knee joint cartilage thickness annually. Results: Knee OA progression was seen in 24/64 knees (37.5%), while OA did not progress or the joint space increased in 40/64 knees (62.5%) (Fig 1). Approximately half of the knees with progression of knee OA were in K-L grade 3 or higher (45.8% * χ2 test), while all grade 1 or 2 patients who showed progression were obese with a BMI ≥27 kg/m2. On the other hand, in the group without knee OA progression, more than three-fourths of the knees were K-L grade 1 and 2 (77.5% * unpaired t-test). The interval between HA injections was shorter in patients without progression of knee OA, and the total dose was larger than in patients with progression (Table 1). Conclusions: Our previous study in OA animal models indicated that intra-articular injection of HA has both symptom-modifying and disease-modifying effects. In this study, the aim was to determine whether HA has these effects in human knees, as well as to determine the long-term treatment course with intra-articular injection of HA. In the OARSI guidelines, the strength of the recommendation for intra-articular injections of HA is 64, which is lower than for intra-articular injection of corticosteroids. In the previous research, HA treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee OA. In this study, 37.5% of the patients showed OA progression despite continuing HA injection. Converted to the annual OA progression ratio, 7.9% of the patients were shown to have knee disease progression annually. Comparing this ratio with the natural course of knee OA, 7% was reported by the Framingham study, with 3% reported by another study. It is difficult to compare this ratio because of the different populations and study designs. However, intra-articular injection of HA may not prevent OA progression. Approximately two-thirds of patients who received intra-articular injection of HA showed no progression or improvement of knee OA. Intra-articular injection of HA may not be effective in patients with K-L grade 3 or higher or BMI ≥27 kg/m2.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Consequences on Private Insurance Coverage: The AAOS Clinical Practice Guidelines and Hyaluronic Acid Injections.

Consequences on Private Insurance Coverage: The AAOS Clinical Practice Guidelines and Hyaluronic Acid Injections.

Platelet-rich plasma versus hyaluronic acid in knee osteoarthritis: A meta-analysis with the consistent ratio of injection.

Osteoarthritis (OA) is an extremely common form of chronic joint disease which can affect the knees and other joints of older adults, leading to debilitating disability in the knee and consequent reduction in quality of life. Intra-articular platelet-rich plasma (PRP) or hyaluronic acid (HA) injections are effective for maintaining long-term beneficial effects without increasing the risk of intra-articular infection. However, few studies have compared the relative value of HA and PRP for OA treatment. PRP is more effective than HA for OA treatment in recent studies of this topic. We systematically searched Medline, SpringerLink, Embase, Pubmed, Clinical Trials.gov, the Cochrane Library, and OVID for all articles published through May 2018. Any study was included that compared the effect of HA and PRP (consistent treatment cycle and frequency of injection) on patient's pain levels and functionality improvements. Review Manager 5.3 was used to analyze data regarding these two primary outcomes. We included 10 total studies in the present meta-analysis. International Knee Documentation Committee (IKDC; MD: 10.37, 95% confidence interval (CI): 9.13 to 11.62, p < 0.00001), Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC; MD: -20.69, 95% CI: -24.50 to -16.89, p < 0.00001, I2 = 94%), and Visual Analogue Scale (VAS; MD: -1.50, 95% CI: -1.61 to -1.38, p < 0.00001, I2 = 90%) differed significantly between the PRP and HA groups. Knee Osteoarthritis Outcome Scores (KOOSs) did not differ significantly (χ2 = 23.53, I2 = 41%, p = 0.11). Our hypothesis appears not to be confirmed because PRP and HA did not differ significantly with respect to KOOS score. However, the IKDC, WOMAC, and VAS scores differed significantly. Thus, based on the current evidence, PRP appears to be better than HA at achieving pain relief and self-reported functional improvement. Ia, meta-analyses of randomized clinical trials.

One-year follow-up of efficacy and cost of repeated doses versus single larger dose of intra-articular hyaluronic acid for knee osteoarthritis.

A recent 3-month randomized, open-label controlled trial found that the intra-articular hyaluronic acid injection (GO-ON®) given as a single dose of 5 mL is as effective and safe as three repeated doses of 2.5 mL in patients with knee osteoarthritis. However, the information on the long-term efficacy and economic implications of the single-dose regimen is still limited. Hence, this follow-up study was designed to compare the effectiveness and costs of the two regimens 12 months following the treatment. All the 127 patients, who received either three repeated doses (n = 64) or a single dose (n = 63) of GO-ON in the previous trial, were followed up in month 12 following the treatment. The effectiveness of both the regimens was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the mean WOMAC scores were compared with those recorded at the baseline and in month 3. Additionally, the total treatment costs of the two regimens, taking account of both direct and indirect costs, were computed and compared. A total of 125 patients (98.4%) completed the assessment. Despite the reduction of the overall mean WOMAC score from 39.24 to 19.93 (p < 0.001) in the first 3 months following the treatment with GO-ON, no further changes were observed up to month 12 (p > 0.95). In the meantime, the two regimens did not differ in the mean WOMAC scores (p = 0.749) and in the subscale scores for pain (p = 0.970), stiffness (p = 0.526), and physical functioning (p = 0.667) in month 12. The cost for single-dose injection was found to be approximately 30% lower compared to the repeated doses. These findings indicate that the single larger dose of GO-ON is as effective as the repeated doses over 12 months, and yet the total treatment cost is lowered.

Safety of Intra-Articular Hyaluronic Acid for Knee Osteoarthritis: Systematic Review and Meta-Analysis of Randomized Trials Involving More than 8,000 Patients.

The objective of this systematic review and meta-analysis was to report the safety of intra-articular hyaluronic acid (IAHA) in patients with symptomatic knee osteoarthritis (OA). We identified randomized controlled trials reporting the safety of IAHA versus IA saline in adults with symptomatic knee OA. Main safety outcomes were adverse events (AEs), local AEs, serious adverse events (SAEs), study withdrawals, and AE-related study withdrawals. A total of 35 randomized controlled trials with 38 group comparisons comprising 8,078 unique patients (IAHA: 4,295, IA saline: 3,783) were included in the meta-analysis. Comparing IAHA with IA saline over a median of 6 months follow-up, there were no differences in the risk of AEs (42.4% vs. 39.7%, risk ratio [RR] = 1.01, 95% CI = 0.96-1.07, P = 0.61), SAEs (1.8% vs. 1.2%, RR = 1.44, 95% CI = 0.91-2.26, P=0.12), study withdrawals (12.3% vs. 12.7%, RR = 0.99, 95% CI = 0.87-1.12, P = 0.83), or AE-related study withdrawals (2.7% vs. 2.1%, RR = 1.37, 95% CI = 0.97-1.93, P = 0.08). Local AEs, all of which were nonserious, were more common with IAHA vs. IA saline (14.5% vs. 11.7%, RR = 1.21, 95% CI = 1.07-1.36, P = 0.003) and typically resolved within days. IAHA was shown to be safe for use in patients with symptomatic knee OA. Compared with IA saline, IAHA is associated with an increased risk of nonserious, transient local reactions. There was no evidence to suggest any additional safety risks of IAHA.

The effectiveness of high molecular weight hyaluronic acid for knee osteoarthritis in patients in the working age: a randomised controlled trial

BackgroundHigh molecular weight (HMW) hyaluronic acid (HA) is a treatment option for knee osteoarthritis (OA). The efficacy of HMW-HA in knee OA is investigated extensively, but the effectiveness in patients in the working age is unknown. Nevertheless, the number knee OA patients in the working age is increasing. Surgical treatment options are less eligible in these patients and productivity losses are high. In this study the effectiveness of intra-articular HMW-HA added to regular non-surgical usual care in everyday clinical practice (UC) compared to UC over 52 weeks in symptomatic knee OA patients in the working age was investigated.MethodsIn this open labelled randomized controlled trial, subjects aged between 18 and 65 years with symptomatic knee OA (Kellgren and Lawrence I-III) were enrolled and randomized to UC + 3 weekly injections with HMW-HA (intervention) or UC only (control). The primary outcome was the between group difference in responders to therapy according to OMERACT-OARSI criteria after 52 weeks. These criteria include the domains pain, knee related function and patient’s global assessment (PGA). Function was evaluated with the KOOS questionnaire. Pain was assessed with the Numeric Rating Scale. Secondary outcome comprised the between group difference on the individual responder domains, as analysed with a random effects model. Odds Ratios (OR) were calculated by logistic regression analysis. Sensitivity analyses were performed.ResultsIn total, 156 subjects were included (intervention group 77, control group 79). Subjects in the intervention group (HMW-HA + UC) were more often responder compared to the controls (UC). Depending on whether pain during rest or pain during activity was included in the responder domains, 57.1% versus 34.2% (p = 0.006) and 54.5% versus 34.2% (p = 0.015) was responder to therapy respectively. The results of the secondary outcome analyses show that scores on individual responder domains over all follow-up moments were statistically significant in favour of the intervention group in the domains pain during rest (δ 0.8, 95%CI 0.2; 1.4, p = 0.010), knee related function (δ − 6.8, 95%CI -11.9; − 1.7, p = 0.010) and PGA (δ − 0.7, 95%CI -0.9; − 0.4, p < 0.0001).ConclusionsIntra-articular HMW-HA added to usual care is effective for knee OA in patients in the working age.Trial registrationwww.trialregister.nl, NTR1651, registered 2009-3-3.