New treatment for Osteoarthritis. Reported By Dr. Humeira Badsha Rheumatologist Dubai, United Arab Emirates

PHILADELPHIA -- Patients who were treated with tanezumab, an investigational monoclonal antibody against nerve growth factor, had relief of osteoarthritis knee pain over the course of a year, researchers said here.
At a dosage of 50 mcg/kg, mean pain scores declined 26 points (SD 30) from a baseline mean of 67 after 16 weeks in the initial randomized, placebo-controlled study, according to Thomas Schnitzer, MD, PhD, of Northwestern University, who presented the findings at a poster session at the American College of Rheumatology's annual meeting.

After another 32 weeks of treatment at that dosage, mean scores declined an additional 9 points, settling at 35 (SD 27) at the end of the extension phase.

Pain scores in patients on higher and lower doses of the drug during the randomized portion appeared to converge toward the mid-30s when they were switched to the 50-mcg/kg dose during the extension.

"Repeated dosing with this compound gives sustained pain relief," Schnitzer said.

Tanezumab's target, nerve growth factor, plays an important role in the development of chronic pain states, such that the pain often takes on a life of its own, Schnitzer said.

Injured and inflamed tissues often show elevated levels of nerve growth factor, which in turns seems to mediate heightened perceptions of pain.

In addition to being studied for osteoarthritis knee pain, tanezumab has also been investigated as a treatment for pain associated with endometriosis, prostatitis, and bone metastases in cancer.

The current osteoarthritis study was an extension of a dose-ranging, placebo-controlled trial that found tanezumab significantly better than placebo in improving patients' walking pain and overall global assessment of response to treatment. That study tested five doses of tanezumab.

In the extension trial, patients on placebo, 10 mcg/kg of tanezumab or 25 mcg/kg of tanezumab said they achieved greater pain relief when switched to the 50 mcg/kg dose of tanezumab.

Schnitzer said patients who had been taking 100 mcg/kg and 200 mcg/kg said they experienced slightly decreased efficacy.

However, the mean pain scores by the end of the study were similar across all the treatment groups, he reported.

"Administration of repeat doses of tanezumab 50 mcg/kg in patients with moderate to severe osteoarthritis knee pain was safe and well tolerated for up to one year," Schnitzer said.

He said 281 patients entered the extension phase of the study. About 40% of the patients were men. The mean age of the group was 59, and 90% were white.

Most adverse events were rated as mild and transient, and none of the serious adverse events experienced in the study were considered drug-related. None of the participants died.

About 11% of the patients discontinued the study for lack of efficacy.

Asked whether a biologic drug could ever be cost-effective as a pain reliever in osteoarthritis -- having no impact on the underlying joint erosion -- Schnitzer said it was not out of the question.

He said it was conceivable that a year's treatment cost with the drug could be in the vicinity of $1,000, which would be competitive with more conventional brand-name drugs.

For example, the COX-2 inhibitor celecoxib (Celebrex) retails for about $1,500 per year at the most common dosage.

Joanne Jordan, MD, MPH, director of the arthritis center at the University of North Carolina in Chapel Hill, N.C., said that an alternative to opioid drugs would be welcome for patients whose pain is not controlled with nonsteroidal anti-inflammatory drugs.

"Patients don't like [opioids]," she said. "They're afraid of them, they worry about dependence."

Jordan agreed that pain in osteoarthritis cases "often doesn't match up with their structural abnormalities," suggesting a neurogenic component that may need to be targeted specifically in therapy.

Poster session discussant Timothy McAlindon, MD, of Tufts Medical Center in Boston, said there was increasing recognition that chronic pain from osteoarthritis may require treatments that go beyond the affected joints.

"We're beginning to recognize that chronic pain [from somatic conditions] has a neurological component," he said.

Treatments targeting pain regulators in the central nervous system are likely to attract more attention from rheumatologists in the future, McAlindon predicted