Intra-articular Hyaluronic Acid for Osteoarthritis of the Knee in the United States: A Systematic Review of Economic Evaluations.

BACKGROUND: The economic impact of intra-articular hyaluronic acid (IAHA) for the treatment of knee pain associated with osteoarthritis (OA) has been evaluated in the United States, but not systematically summarized. OBJECTIVE: We reviewed the literature to determine the economic impact of IAHA for pain associated with knee OA in the United States. METHODS: A literature review was performed in PubMed (including MEDLINE and MEDLINE In-Process), Embase, the Cochrane Database of Systematic Reviews, and National Health Service Economic Evaluation Database and was limited to English language human studies published from January 2000 to October 2020. RESULTS: The literature search identified 215 unique abstracts; of these, 47 were selected for full-text review and 21 studies met the inclusion criteria. Intra-articular hyaluronic acid injections delayed progression to total knee arthroplasty (TKA), and repeated courses of treatment successfully delayed TKA by more than 5 years. Intra-articular hyaluronic acid was found to reduce the use of pain medications overall and reduce the number of patients receiving opioid prescriptions by 6% (P < .001). Several studies showed that IAHA is more cost-effective in treating pain associated with knee OA compared with conventional care with nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, and corticosteroids, and several authors concluded that IAHA should be the dominant treatment strategy. CONCLUSIONS: Current studies suggest that IAHA may reduce the use of pain medications, such as NSAIDs and opioids, and impact time to TKA procedures, thus potentially decreasing overall treatment costs of knee OA over time. Furthermore, IAHA was determined to be cost-effective against NSAIDs, corticosteroids, analgesics, and conservative treatment. As the safety and efficacy of IAHA for knee OA have been well established, the findings from our literature review may be used to inform future economic evaluations.

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

High-concentration nonavian high-molecular weight hyaluronan injections and time-to-total knee replacement surgery.

Aim: To examine the time-to-total knee replacement (TKR) surgery among patients with high-concentration nonavian high-molecular-weight hyaluronan injection (HMW-HA) compared with those without HA injections. Materials & methods: Using MarketScan® Commercial claims all patients aged 18-64 who underwent TKR surgery between 2008 and 2017 were identified. Time-to-TKR surgery was compared between patients receiving Orthovisc® (Anika Therapeutics Inc. Bedford MA, USA, referred to as nonavian HMW-HA) injections and patients who did not receive an HA injection. Results: The median time-to-TKR surgery was 893 days in the nonavian HMW-HA cohort and 399 days in the non-HA cohort (p < 0.001), a difference of 494 days (16.2 months). Conclusion: This study demonstrates that the time-to-TKR surgery is 16.2 months longer in patients who received treatment with nonavian HMW-HA injections.

Real-world impact of the high concentration non-avian high molecular weight hyaluronan on pain medication use among osteoarthritis patients.

Objective: A prior study found that hyaluronic acid (HA) treatment may help reduce pain medication use (such as steroids, non-steroidal anti-inflammatory drugs [NSAIDs] and opioids) among knee osteoarthritis (OA) patients in the real-world setting. This study aims to update the prior study results to include only the high concentration non-avian high molecular weight hyaluronan (HMW-HA) injectables using data from recent years.Study design: This was a retrospective cohort study utilizing IBM MarketScan Commercial data from 2008 to 2015.Methods: Commercially insured patients between 18 and 64 years of age who received high concentration non-avian HMW-HA (Orthovisc1) between 1 January 2008 and 30 June 2015 were identified. Utilization of three prescription pharmacotherapies commonly used in the treatment for knee OA - NSAIDs, corticosteroid injections and opioids - in the 6 month pre and post periods was assessed. Utilization was measured as number of prescriptions and any prescription (yes/no). The independent variable was receiving the high concentration non-avian HMW-HA injection. Paired sample t-test and McNemar's test were used to assess pre-post changes.Results: The utilization of NSAIDs and steroids prescriptions was reduced significantly during the post period among the study cohort. The proportion of patients filling these prescriptions during the post period was also reduced (p < .001). In addition, the number of patients getting any opioid prescriptions was reduced significantly during the post period (p < .001).Conclusions: Based on this retrospective cohort study, the high concentration non-avian HMW-HA may offer effective pain alleviation among knee OA patients while reducing prescription pain medications such as steroids, NSAIDs and opioids.

Association between Hyaluronic Acid Injections and Time-to-Total Knee Replacement Surgery.

This study assessed the association between hyaluronic acid (HA) injections and time-to-total knee replacement (TKR) surgery for patients with knee osteoarthritis (OA). Patients 18 to 64 years of age who had TKR surgery between January 1, 2006 and December 31, 2011 were identified from the MarketScan Commercial claims database. All patients had 6 years or more of continuous enrollment prior to TKR surgery. There were two cohorts (1) patients with HA injections prior to TKR surgery and (2) patients who did not have HA injections prior to TKR surgery. Time-to-TKR was defined as the total days from the date of diagnosis of knee OA on the patient's first visit to an orthopedic surgeon to the date of TKR surgery. Results included 22,555 patients who had TKR surgery: 14,132 in the non-HA and 8,423 in the HA cohort. In this retrospective analysis of patients undergoing TKR, the median Time-to-TKR surgery was 326 days for the non-HA and 908 days for the HA cohort, a difference of 582 days. Those receiving HA injections had a median 1.6-year longer Time-to-TKR surgery versus those who did not receive HA injections. These results have both clinical and economic implications.