Abstract
BackgroundThe prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA. Systematic reviews of treatment efficacy and adverse events (AEs) of hyaluronic acid (HA) injections report conflicting evidence about the balance of benefits and harms. We review evidence on efficacy and AEs of intraarticular viscosupplementation with HA in older individuals with knee osteoarthritis and account for differences in these conclusions from another systematic review.MethodsWe searched PubMed and eight other databases and gray literature sources from 1990 to December 12, 2014. Double-blind placebo-controlled randomized controlled trials (RCTs) reporting functional outcomes or quality-of-life; RCTs and observational studies on delay/avoidance of arthroplasty; RCTs, case reports, and large cohort studies and case series assessing safety; and systematic reviews reporting on knee pain were considered for inclusion.A standardized, pre-defined protocol was applied by two independent reviewers to screen titles and abstracts, review full text, and extract details on study design, interventions, outcomes, and quality. We compared our results with those of a prior systematic review and found them to be discrepant; our analysis of why this discrepancy occurred is the focus of this manuscript.ResultsEighteen RCTs reported functional outcomes: pooled analysis of ten placebo-controlled, blinded trials showed a standardized mean difference of −0.23 (95 % confidence interval (CI) −0.45 to −0.01) favoring HA at 6 months. Studies reported few serious adverse events (SAEs) and no significant differences in non-serious adverse events (NSAEs) (relative risk (RR) [95 % CI] 1.03 [0.93–1.15] or SAEs (RR [95 % CI] 1.39 [0.78–2.47]). A recent prior systematic review reported similar functional outcomes, but significant SAE risk. Differences in SAE inclusion and synthesis accounted for the disparate conclusions.ConclusionsTrials show a small but significant effect of HA on function on which recent systematic reviews agree, but lack of AE synthesis standardization leads to opposite conclusions about the balance of benefits and harms. A limitation of the re-analysis of the prior systematic review is that it required imputation of missing data.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0363-9) contains supplementary material, which is available to authorized users.
Highlights
The prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA
In the course of comparing our results to a previous systematic review on the same topic, we identified a situation in which differences in how adverse events (AEs) are synthesized have resulted in differences in estimates of the risk of harms, which in turn result in completely different conclusions regarding the balance of benefits and harms for the use of hyaluronic acid (HA), in spite of reporting similar results on effectiveness for functional outcomes
18 randomized trials reported on the effects of HA compared to sham-injected placebo control, another HA, or some other active treatment on function, as measured by the Western OntarioMcMaster Universities Arthritis Index (WOMAC [17]), the Lequesne Index [18], the Knee Injury and Osteoarthritis Outcomes Score (KOOS [19]), or Activities of Daily Living, among patients whose average age was 65 or older
Summary
The prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA. We review evidence on efficacy and AEs of intraarticular viscosupplementation with HA in older individuals with knee osteoarthritis and account for differences in these conclusions from another systematic review. In the 2012 update to their 2000 guidelines for the treatment of osteoarthritis of the knee, hip, and hand, the American College of Rheumatology conditionally recommended HA injections for patients who had an inadequate response to initial therapy [5]. The 2013 American Academy of Orthopedic Surgeons guidelines for the treatment of knee osteoarthritis recommend against the use of HA to treat patients with symptomatic conditions [6]
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