Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials.

Strand, Vibeke; McIntyre, Louis F; Beach, William R; Miller, Larry E.; Block, Jon E.

doi:10.2147/JPR.S83076

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Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials.

Author(s): Vibeke Strand, Louis McIntyre, William Beach, Larry E. Miller, Jon E. Block

Publication date: 2015

Journal: Journal of Pain Research

Keywords: hyaluronic acid, intra-articular, viscosupplementation

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Abstract

Intra-articular injection of hyaluronic acid is a common, yet controversial, therapeutic option for patients with knee osteoarthritis (OA). The purpose of this research was to determine the safety and efficacy of US-approved viscosupplements for symptomatic knee OA.

Most cited references 53

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Pathogenesis and management of pain in osteoarthritis.

Paul A Dieppe, L Stefan Lohmander (2005)

The term osteoarthritis describes a common, age-related, heterogeneous group of disorders characterised pathologically by focal areas of loss of articular cartilage in synovial joints, associated with varying degrees of osteophyte formation, subchondral bone change, and synovitis. Joint damage is caused by a mixture of systemic factors that predispose to the disease, and local mechanical factors that dictate its distribution and severity. Various genetic abnormalities have been described, but most sporadic osteoarthritis probably depends on minor contributions from several genetic loci. Osteoarthritic joint damage may be associated with clinical problems, but the severity of joint disease is only weakly related to that of the clinical problem. For this reason the associations and pathogenesis of pain are in as much need of investigation as joint damage. Subchondral bone and synovium may be responsible for nociceptive stimuli, and peripheral neuronal sensitisation is an important feature, and can result in normal activities (such as walking) causing pain. Central pain sensitisation can also occur, and psychosocial factors are important determinants of pain severity. We present a stepwise approach to the management of osteoarthritis.

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Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data

Jan O Friedrich, Neill KJ Adhikari, Joseph Beyene (2007)

Background Meta-analysis handles randomized trials with no outcome events in both treatment and control arms inconsistently, including them when risk difference (RD) is the effect measure but excluding them when relative risk (RR) or odds ratio (OR) are used. This study examined the influence of such trials on pooled treatment effects. Methods Analysis with and without zero total event trials of three illustrative published meta-analyses with a range of proportions of zero total event trials, treatment effects, and heterogeneity using inverse variance weighting and random effects that incorporates between-study heterogeneity. Results Including zero total event trials in meta-analyses moves the pooled estimate of treatment effect closer to nil, decreases its confidence interval and decreases between-study heterogeneity. For RR and OR, inclusion of such trials causes small changes, even when they comprise the large majority of included trials. For RD, the changes are more substantial, and in extreme cases can eliminate a statistically significant effect estimate. Conclusion To include all relevant data regardless of effect measure chosen, reviewers should also include zero total event trials when calculating pooled estimates using OR and RR.

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Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and meta-analysis.

Christopher H Schmid, S Natov, R R Bannuru … (2009)

To compare the efficacy of intraarticular hyaluronic acid with corticosteroids for knee osteoarthritis (OA). Our data sources were Medline, EMBASE, CINAHL, BIOSIS, and the Cochrane database, as well as hand- searched reviews, manuscripts, and supplements. For unpublished data we used author contacts. Randomized trials that reported effects of intraarticular hyaluronic acid versus corticosteroids on knee OA were selected based on inclusion criteria. Two reviewers extracted data independently. Using a random-effects model, we computed effect sizes for pain change from baseline at 2, 4, 8, 12, and 26 weeks. We also performed multivariate analyses accounting for within and between-study covariance. We performed sensitivity analyses for trials that reported intent-to-treat (ITT) analysis and blinding, and directly compared Hyalgan with methylprednisolone. The 7 eligible trials included 606 participants. Five reported ITT analyses. At week 2 the effect size was -0.39 (95% confidence interval [95% CI], -0.65, -0.12) favoring corticosteroids; at week 4 it was -0.01 (95% CI -0.23, 0.21) suggesting equal efficacy. At week 8 the effect size was 0.22 (95% CI -0.05, 0.49) favoring hyaluronic acid, and at week 12 it was 0.35 (95% CI 0.03, 0.66) favoring hyaluronic acid. At week 26 the effect size was 0.39 (95% CI 0.18, 0.59), favoring hyaluronic acid. The multivariate analyses and sensitivity analyses generated consistent results. From baseline to week 4, intraarticular corticosteroids appear to be relatively more effective for pain than intraarticular hyaluronic acid. By week 4, the 2 approaches have equal efficacy, but beyond week 8, hyaluronic acid has greater efficacy. Understanding this trend is useful to clinicians when treating knee OA.