Background: Viscosupplementation treatment for osteoarthritis of the knee can involve intraarticular injections of either hyaluronic acid (HA) or a modified HA called hylan. Because hylans have a greater molecular weight than HAs, they are slower to clear from the injected joint. In theory, this can enhance their effectiveness in treating symptoms of osteoarthritis. Metaanalyses have reported better pain reduction with hylans than with HAs; however, multiple case reports have found that hylan injections are more frequently associated with acute pain flares. Jüni and colleagues compared hylan with HA in terms of safety, effectiveness, and cost in treating osteoarthritis.

The Study: The authors conducted an industry-free, patient-blind, randomized controlled trial comparing hylan with HAs. Men and nonpregnant women with radiographically confirmed osteoarthritis of the knee were eligible if they had experienced symptoms for at least six months and were in pain on most days during the preceding three months that was not adequately controlled with acetaminophen or nonsteroidal anti-inflammatory drugs.

The study randomly assigned patients to receive a three-dose cycle of one of three intraarticular-injected agents: high molecular weight hylan, a medium-weight avian HA, or a low-weight bacterial HA. Patients received one treatment cycle per knee during the first six months of the study; one half of each group (selected randomly) received a second three-injection cycle during the second six months. Pain status was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and six months after injections. Comparisons were made among the three groups, but because no differences were found in effectiveness or safety between the two HA agents, their results were reported in aggregate compared with the hylan group.

Results: Of the 660 participants, 66.2 percent were female. The mean age of the group was 63.4 years, and the mean body mass index was 28.3. The patients had similar baseline characteristics. At the six-month follow-up, no differences were found between the hylan and HA groups regarding WOMAC pain scores, the need for pain medication, or the need for other treatments, including surgical interventions.

Patients in the hylan group experienced significantly more local adverse events (e.g., pain flares) than did those in the two HA groups (9.5 percent versus 7.3 percent, respectively). This trend was even more pronounced in patients receiving a second injection cycle (9.1 percent vs. 2.7 percent, respectively). Serious adverse events were not statistically different between groups, although there was one instance of anaphylaxis in a patient receiving hylan. There were no differences in effectiveness or adverse events between patients with unilateral or bilateral knee osteoarthritis.

Conclusion: Hylan and HA viscosupplementation agents are equally effective in treating symptoms of knee osteoarthritis, but hylan was associated with higher rates of local adverse events, particularly post-injection pain flares. Because of the higher rates of pain flares and the higher costs of hylan, the authors concluded that there is no rationale for the continued use of hylan in patients with osteoarthritis of the knee.