Hyaluronate Injections for Osteoarthritis
March 1, 2000 4 minutes read
Hyaluronate Injections for Osteoarthritis
Abstract & Commentary
Synopsis: Although some patients improved with hyaluronate injections, there was little difference compared to placebo, and the study had serious design flaws.
Source: Altman RD, Moskowitz R. Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: A randomized clinical trial. J Rheumatol 1998;25(11):2203-2212.
Injection therapy with hyaluronate (ha) has become a popular addition to the treatment options for osteoarthritis since the introduction of Hyalgan and Synvisc to the U.S. market about a year ago. Yet little is known about its exact mechanism of action, and comparative studies are few. One of the most widely cited studies to examine the effectiveness of HA therapy was by Altman and Moskowitz. They conducted a double-blind, masked-observer, placebo-controlled, randomized trial on 495 patients from 15 academic medical centers in the United States. Three treatment groups were compared for pain relief. All groups received a series of five weekly injections of some type plus oral tablets. The HA group received intra-articular hyaluronate and oral placebo. The Naproxen group received subcutaneous sham injections with Lidocaine and Naproxen 500 mg po bid. The placebo group received intra-articular saline and oral placebo.
Patients were assessed at six months for pain relief and function during a 50-foot walk. Pain experienced by the HA group improved significantly compared to the placebo group but not compared to the Naproxen group. At six months, the percentage of patients who reported they had slight pain or were pain free was 48% for the HA group, 39% for the Naproxen group, and 33% for the placebo group. A 20-mm improvement in Visual Analogue Scale (VAS) scores was noted for the duration of the study in 56% of HA patients vs. 41% of placebo patients. About one-third of the patients in each group dropped out of the study because of pain at the injection site (4% of HA group), gastrointestinal intolerance (9% of Naproxen group), or failure to complete the study. If all randomized patients are analyzed (intent-to-treat analysis), there was a 20-mm improvement in VAS pain scores for 28% of the placebo group, 31% of the Naproxen group, and 36% of the HA group. There were no significant differences between groups for range of motion, effusions, or function.
Comment by David R. Diduch, MS, MD
All too often we have seen in our offices the 45-year-old former athlete, 25 years after open meniscectomy, with an early varus, arthritic knee, who is willing to try anything to put off a joint replacement. Because osteoarthritis of the knee is so common, any new intervention tends to get a lot of attention and patient demand. I think we all remember how the lay press misrepresented chondrocyte autotransplantation a few years ago, resulting in a flood of patients carrying news clippings for their appointments. It is our duty as clinicians to educate our patients about the proper place of new technology and to prescribe it appropriately. However, problems arise when the scientific literature is sparse compared to the public demand.
This seems to be the case with the new viscoelastic injection therapies such as hyaluronate. The studies are few and the numbers not impressive. Who would be happy with a surgical procedure that, at best, could improve 56% of patients compared to 41% with a sham operation (placebo)? Yet these agents have been used widely in the orthopaedic and primary care communities.
There is a definite need for quality outcome studies to measure the effectiveness of these agents, especially for longer than the six months of follow-up in this study. What happens next? Do we repeat the series every six to 12 months? Another article by Kotz and Kolarz showed that 55% of patients had relief through 12 months and about 12% of patients repeated the series of injections during this period.1 However, nearly 45% of patients dropped out of the study for various reasons before completion. Considering one-third of patients in each group did not complete the Altman study, these drop-out rates are serious flaws that make all conclusions highly suspect. In addition, the Altman study was sponsored by the pharmaceutical company that makes the drug being studied, potentially compromising objectivity.
However, there does appear to be a measurable benefit to hyaluronate injections, with some patients demonstrating clinical improvement. Whether the potential improvement justifies the morbidity of five injections and approximately $1000 in cost must be determined on an individual basis. Certainly, in some cases we have run out of other reasonable options. There are no mechanical signs to suggest meniscal pathology or loose bodies as responsible for the symptoms, the patients have not responded to NSAIDs or steroid injections, physical therapy and activity modification, and they are too young or not sufficiently arthritic to warrant a joint replacement. When I am backed into a corner like this, in my opinion these agents can be considered. However, patients must be educated to make an informed decision and, at present, the numbers in these studies are about the best they can expect.
Clearly, these are not first-line agents. Better outcome studies will help to determine the most appropriate place in our treatment armamentarium for viscoelastic injection therapy. This may be one case in which the regulations of managed care work to the benefit of the patient.
Reference
1. Kotz R, Kolarz G. Intra-articular hyaluronic acid: Duration of effect and results of repeated treatment cycles. Am J Orthop 1999;28(11Suppl):5-7.
In the Altman study, 56% of patients receiving hyaluronate injections improved their pain scores at six months. What percentage of patients receiving placebo injections reported the same benefit?
a. 5%
b. 11%
c. 15%
d. 41%
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