The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis

Abstract Background Intra-articular hyaluronic acid (IA-HA) is a common therapy used to treat knee pain and suppress knee inflammation in knee osteoarthritis (OA), typically prescribed in regimens ranging from a single injection to 5 weekly injections given once weekly. We conducted a systematic review to determine the efficacy of IA-HA, with subgroup analyses to explore the differences in knee pain and adverse events (AEs) across different dosing regimens. Methods We conducted a systematic search of the literature to identify studies evaluating IA-HA for the management of knee OA compared to IA-saline. Primary outcome measure was the mean knee pain score at 13 Weeks (3 months) or 26 weeks (6 months). Secondary outcome was the number of treatment-related AEs and treatment-related serious adverse events (SAEs). We evaluated differences in levels of pain and AEs/SAEs between dosing regimens compared to IA-Saline. Results Thirty articles were included. Overall, IA-HA injections were associated with less knee pain compared to IA-Saline injections for all dosing regimens. 2–4 injections of IA-HA vs. IA-Saline produced the largest effect size at both 3-months and 6-months (Standard mean difference [SMD] = −0.76; −0.98 to −0.53, 95% CI, P < 0.00001, and SMD = −0.36; −0.63 to −0.09 95% CI, P = 0.008, respectively). Additionally, single injection studies yielded a non-significant treatment effect at 3 and 6 months, while ≥5 5 injections demonstrated a significant improvement in pain only at 6 months. Five or more injections of IA-HA were associated with a higher risk of treatment-related AEs compared to IA-Saline (Risk ratio [RR] = 1.67; 1.09 to 2.56 95% CI, p = 0.02), which was a result not seen within the 1 and 2–4 injection subgroups. Conclusion Overall, 2–4 and ≥5 injection regimens provided pain relief over IA-Saline, while single injection did not. Intra-articular injections of HA used in a 2–4 injection treatment regimen provided the greatest benefit when compared to IA-Saline with respect to pain improvement in patients with knee OA, and was generally deemed safe with few to no treatment-related AEs reported across studies. Future research is needed to directly compare these treatment regimens

AMSSM Scientific Statement Concerning Viscosupplementation Injections for Knee Osteoarthritis: Importance for Individual Patient Outcomes.

OBJECTIVE: Osteoarthritis (OA) is a disabling disease that produces severe morbidity reducing physical activity. Our position statement on treatment of knee OA with viscosupplementation injection [hyaluronic acid (HA)] versus steroid [intra-articular corticosteroid (IAS)] and placebo [intra-articular placebo (IAP)] is based on the evaluation of treatment effect by examining the number of subjects within a treatment arm that met the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria, which is different and more relevant than methods used in other reviews which examined if the average change across the treatment groups was clinically different. DATA SOURCES: We performed a systematic literature search for all relevant articles from 1960 to August 2014 in the MEDLINE, EMBASE, and Cochrane CENTRAL. We performed a network meta-analysis (NMA) of the relevant literature to determine if there is a benefit from HA as compared with IAS and IAP. MAIN RESULTS: Eleven articles met the inclusion criteria from the search strategy. On NMA, those subjects receiving HA were 15% and 11% more likely to respond to treatment by the OMERACT-OARSI criteria than those receiving IAS or IAP, respectively (P \u3c 0.05 for both). CONCLUSIONS: In light of the aforementioned results of our NMA, the American Medical Society for Sport Medicine recommends the use of HA for the appropriate patients with knee OA

American Medical Society for Sports Medicine (AMSSM) position statement: interventional musculoskeletal ultrasound in sports medicine.

The use of diagnostic and interventional ultrasound has significantly increased over the past decade. A majority of the increased utilization is by nonradiologists. In sports medicine, ultrasound is often used to guide interventions such as aspirations, diagnostic or therapeutic injections, tenotomies, releases, and hydrodissections. This American Medical Society for Sports Medicine (AMSSM) position statement critically reviews the literature and evaluates the accuracy, efficacy, and cost-effectiveness of ultrasound-guided injections in major, intermediate, and small joints, and soft tissues, all of which are commonly performed in sports medicine. New ultrasound-guided procedures and future trends are also briefly discussed. Based upon the evidence, the official AMSSM position relevant to each subject is made

Knee Osteoarthritis Treatment Costs in the Medicare Patient Population.

BackgroundSeveral nonoperative options have been recommended for the treatment of knee osteoarthritis (OA), with varying degrees of evidence. Adhering to the American Academy of Orthopaedic Surgeons clinical practice guidelines has been suggested to decrease direct treatment costs by 45% in the year before knee arthroplasty, but this does not consider the cost of the entire episode of care, including the cost of surgery and postsurgery care.ObjectivesTo analyze the total treatment costs after a diagnosis of knee OA, as well as the proportion of arthroplasty interventions as part of the total knee OA-related costs, and whether the total costs differed for patients who received intra-articular hyaluronic acid and/or had knee arthroplasty.MethodsWe identified patients newly diagnosed with knee OA using the 5% Medicare data sample from January 2010 to December 2015. Patients were excluded if they were aged &lt;65 years, had incomplete claim history, did not reside in any of the 50 states, had claim history &lt;12 months before knee OA diagnosis, or did not enroll in Medicare Part A and Part B. The study analyzed knee OA-related costs from a payer perspective in terms of reimbursements provided by Medicare, as well as the time from the diagnosis of knee OA to knee arthroplasty for patients who had knee arthroplasty, and the time from the first hyaluronic acid injection to knee arthroplasty for those who received the injection. We compared patients who received hyaluronic acid and those who did not receive hyaluronic acid injections. Patients who received hyaluronic acid injection who subsequently had knee arthroplasty were also compared with those who did not have subsequent knee arthroplasty.ResultsOf the 275,256 patients with knee OA, 45,801 (16.6%) received a hyaluronic acid injection and 35,465 (12.9%) had knee arthroplasty during the study period. The median time to knee arthroplasty was 16.4 months for patients who received hyaluronic acid versus 5.7 months for those who did not receive hyaluronic acid. Non-arthroplasty-related therapies and knee arthroplasty accounted for similar proportions of knee OA-related costs, with hyaluronic acid injection comprising 5.6% of the total knee OA-related costs. For patients who received hyaluronic acid injections and subsequently had knee arthroplasty, hyaluronic acid injection contributed 1.8% of the knee OA-related costs versus 76.6% of the cost from knee arthroplasty. Patients who received hyaluronic acid injections and did not have knee arthroplasty incurred less than 10% of the knee OA-related costs that patients who had surgery incurred.ConclusionAlthough limiting hyaluronic acid use may reduce the knee OA-related costs, in this study hyaluronic acid injection only comprised a small fraction of the overall costs related to knee OA. Among patients who had knee arthroplasty, those who received treatment with hyaluronic acid had surgery delayed by a median of 10.7 months and associated costs for a significant period. The ability to delay or avoid knee arthroplasty altogether can have a substantial impact on healthcare costs

AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: importance for individual patient outcomes.

Osteoarthritis (OA) is a disabling disease that produces severe morbidity reducing physical activity. Our position statement on treatment of knee OA with viscosupplementation injection (hyaluronic acid, HA) versus steroid (intra-articular corticosteroids, IAS) and placebo (intra-articular placebo, IAP) is based on the evaluation of treatment effect by examining the number of participants within a treatment arm who met the Outcome Measures in Rheumatoid Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) criteria, which is different and more relevant than methods used in other reviews which examined if the average change across the treatment groups were clinically different. We performed a systematic literature search for all relevant articles from 1960 to August 2014 in the MEDLINE, EMBASE and Cochrane CENTRAL. We performed a network meta-analysis (NMA) of the relevant literature to determine if there is a benefit from HA as compared with IAS and IAP. 11 papers met the inclusion criteria from the search strategy. On NMA, those participants receiving HA were 15% and 11% more likely to respond to treatment by OMERACT-OARSI criteria than those receiving IAS or IAP, respectively (

Additional file 1: of The efficacy of multiple versus single hyaluronic acid injections: a systematic review and meta-analysis

Literature Search Strategy. (DOCX 15 kb

A comparison of treatment effects for nonsurgical therapies and the minimum clinically important difference in knee osteoarthritis

© 2019 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED. Background: The minimum clinically important difference (MCID) was developed to ascertain the smallest change in an outcome that patients perceive as beneficial. The objectives of the present review were (1) to compare the MCIDs for pain assessments used among guidelines and meta-analyses investigating different nonsurgical therapies for knee osteoarthritis and (2) to compare the effect estimates of different nonsurgical interventions against a single commonly-utilized MCID threshold. Methods: Systematic and manual searches were conducted to identify guidelines and meta-analyses evaluating pain outcomes for nonsurgical knee osteoarthritis interventions. Individual treatment effects for pain were presented on a common scale (the standardized mean difference [SMD]). To evaluate the perception of the relative benefit of each nonsurgical treatment, the variation in MCIDs selected from the published MCID literature was assessed. Results: Thirty-seven guidelines and meta-analyses were included. MCIDs were often presented as an SMD or a mean difference (MD) on a validated scale and varied in magnitude across sources. This analysis demonstrated that intra-articular hyaluronic acid, intra-articular corticosteroids, and acetaminophen all had relatively larger effect sizes than topical nonsteroidal anti-inflammatory drugs (NSAIDs). Higher-molecular-weight intra-articular hyaluronic acid had a greater relative effect compared with both non-selective and cyclooxygenase-2-selective oral NSAIDs. Evaluating the treatment effect estimates against a commonly utilized MCID revealed similarities in which observations attained clinical significance among treatments; however, this observation varied across the range of reported MCIDs. Conclusions: The present review confirmed the variability in the MCIDs for pain assessments that are used across guidelines and meta-analyses evaluating nonsurgical interventions for knee osteoarthritis. This variability may yield conflicting treatment recommendations, ranging from rejecting treatments that are indeed efficacious to accepting treatments that may not be beneficial. Additional research is required to determine why some nonsurgical therapies are more consistently recommended in knee osteoarthritis guidelines than others as these findings suggest similarities in their effect estimates for pain. Relevant stakeholders need to reach a consensus on a standard approach to determining the MCIDs for these therapies to ensure that appropriate and effective treatment options are available to patients prior to invasive surgical intervention

Evaluating the real-world effectiveness of belimumab in patients with SLE using SLE-related laboratory values and rheumatoid arthritis-derived disease activity measures: RAPID3, swollen joint count and tender joint count

Objective To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values.Methods This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment.Results Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values.Conclusions In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation