New research findings that are changing clinical practice APPLIED EVIDENCE

Objective To evaluate the efficacy of intra-articular viscosupplementation therapy with hyaluronic acid for pain relief of knee osteoarthritis, we conducted a meta-analysis of randomized, doubleblinded, placebo-controlled trials. Methods We searched systematically for randomized, double-blinded, placebo-controlled trials of hyaluronic acid (hyaluronan and hylan G-F20) for pain relief of knee osteoarthritis. Studies reporting pain visual analogue scale (VAS) differences were included in the meta-analysis. Changes in pain were measured by VAS for placebo and treatment, and summary estimates of the differences between the 2 arms were calculated at 1 week, 5 to 7 weeks, 8 to 12, and 15 to 22 weeks after the last intra-articular injection. Sources of heterogeneity were assessed using information on quality score, type of viscosupplementation, and VAS change Hyaluronic acid injections relieve knee pain This meta-analysis shows good therapeutic effect for between 5 and 12 weeks Hyaluronic acid injections relieve knee pain ▲ Pain decreased significantly at 5 to 7 weeks and at 8 to 12 weeks after the last injection, as measured by VAS VOL 54, NO 9 / SEPTEMBER 2005 759 w w w. j f p o n l i n e . c o m FAST TRACK agents, or to lifestyle modifications such as weight reduction and exercise. Hyaluronic acid injections may also be indicated when knee surgery must be delayed for middle-aged persons. In spite of the Food and Drug Administration’s approval of this therapy, uncertainty about its efficacy exists among the medical community. A recent meta-analysis of the effectiveness of intraarticular hyaluronic acid for knee osteoarthritis that included 22 published and unpublished, English and non-English, single or double-blinded, randomized controlled trials in humans showed that hyaluronic acid has only a small effect on pain relief when compared with placebo. We provide here a stringent test of the efficacy of viscosupplementation for relieving knee pain from osteoarthritis with a meta-analysis that includes only data from randomized, double-blinded, controlled trials of hyaluronic acid that measured pain using a visual analogue scale (VAS), the most widely accepted method for pain evaluation. ■ Methods Selection of studies We identified clinical trials of viscosupplementation with hyaluronic acid in humans published in English from 1965 through August 2004 through a computerized literature search of Medline. The keyword used was “hyaluronic acid,” which was combined with “trial” or “osteoarthritis knee” or “viscosupplementation.” We conducted an additional manual search of the reference lists of included articles and review articles. We also searched the Cochrane Library and websites of the Agency for Healthcare Research and Quality (AHRQ) for information on hyaluronic acid in knee osteoarthritis. We identified 1872 articles with this search process. Of the 1872 articles, we identified by title and abstract 33 that might be pertinent to this study, including 17 randomized trials. We excluded reviews, meta-analyses, comparison trials, and trials reporting VAS as part of the WOMAC (Western Ontario McMaster Universities Index) scale. We attempted to contact authors of the studies ILLUSTRATION BY: KEVIN SOMERVILLE Balazs first proposed hyaluronic acid as a treatment for patients with arthritic diseases in 1942. In the early 1970s, therapeutic studies were begun to test the efficacy of hyaluronic acid on knee osteoarthritis. The results were encouraging and side effects were few. With the FDA’s approval in 1998, intra-articular “viscosupplementation” with hyaluronic acid—also called hyaluronan or hyaluronate, and the hylan derivatives of hyaluronic acid—is a welcome option for many of the 16 million older Americans with osteoarthritis of the knee. Long time coming