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NEW YORK (Reuters Health) – Intra-articular injections of hyaluronate sodium appear to provide more relief of pain associated with physical activity due to osteoarthritis of the knee than treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or placebo.

In the Archives of Internal Medicine for February 11, Canadian investigators report the results of a placebo-controlled trial involving 120 patients with osteoarthritis of the knee.

Dr. Robert John Petrella, of the University of Western Ontario in London, Canada, and associates randomly assigned patients to treatment with hyaluronate sodium, 2 mL of a 10 mg/mL solution, administered at baseline and weeks 1 and 2; oral diclofenac 75 mg plus misoprostol 200 µg; hyaluronate, NSAIDs and placebo; or placebo only.

As assessed by the Western Ontario McMaster Universities Index, all three treatment groups reported significantly reduced pain and physical disability at 4 weeks. Only the group treated with hyaluronate plus NSAIDs exhibited significantly more pain relief at week 12 than at week 4. Both groups treated with hyaluronate improved in terms of physical disability between weeks 4 and 12.

Dr. Petrella's group assessed patient physical functioning using self-paced walking and stepping tests. Patients were asked to walk for 40 meters or step up and down 20 times at a "normal" or comfortable pace.

The two viscosupplementation groups walked faster and exhibited greater oxygen uptake at week 4 than the other two groups. At week 12, pain after the walking test was significantly lower than at week 4 in those treated with hyaluronate alone and unchanged among those treated with hyaluronate plus NSAIDs. Patients that did not receive intra-articular injections experienced significantly more pain after the walking test at week 12 than at week 4.

Thus, the investigators write, "The effect of hyaluronate sodium on activity-related pain and functional performance seems to improve with time from intervention compared with the effect of NSAIDs, which does not show continued improvement after 4 weeks of treatment."

However, Drs. David T. Felson and Jennifer J. Anderson, of the Boston Medical Center, disagree with the statistical analysis put forward by Dr. Petrella and his associates, who used repeated-measures analysis of covariance to determine the effects of treatments. Analyses were adjusted for prerandomization baseline factors.

In contrast, when Drs. Felson and Anderson used a factorial design analysis and within-group sums of squares, "neither the main effects of hyaluronate sodium or NSAIDs nor their interaction were statistically significant."

The editorialists back up their comments by referring to three previously published trials, each containing more than 200 subjects, which compared hyaluronate sodium treatment with placebo injection. Drs. Felson and Anderson report that none of these three trials showed significant differences between treatment and placebo.

"This was not a large enough cohort to be analyzed in that way," Dr. Petrella told Reuters Health in defense of his findings. Rather, it was intended as a within-group analysis, he said.

"I do believe that hyaluronate sodium does make a clinically significant difference in pain and function," he emphasized. Osteoarthritis patients are "willing to undergo repeated injections, and most have to pay for the treatment themselves, so they must feel that something good is happening."

Dr. Petrella discussed the three types of patient responses he typically sees. "For 10% to 20% of patients, injection therapy makes no difference" in their symptoms, he said.

In contrast, "60% to 75% will come in and get more relief than they've experienced with any other product at that point." He added that some of these patients even report complete relief, though it usually only lasts about 6 months to 1 year.

About 5% of patients never return for treatment. "Whether it's because it relieved all their symptoms or did not help at all, I don't know."

He added that patient response tends to reflect how advanced their condition is. "If their x-ray shows severe changes, or they describe significant symptoms, a lot of pain medication use and restricted mobility," they tend not to respond well to hyaluronate.