ACR: Tanezumab Keeps OA Knee Pain Under Control

ACR: Tanezumab Keeps OA Knee Pain Under Control

By John Gever, Senior Editor, MedPage Today
Published: October 23, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Earn CME/CE credit
for reading medical news

Action Points
Explain to interested patients that the pain associated with osteoarthritis is often treated with opioids when nonsteroidal anti-inflammatory drugs such as naproxen are ineffective. Tanezumab is being studied as an alternative.


Explain that tanezumab is not FDA approved for any purpose and is available only in a clinical trial setting.


Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
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.

The study was funded by Pfizer.

Schnitzer reported relationships with Logical Therapeutics, Horizon Therapeutics, Merck, NicOx, Winston Laboratories, Solstice, Santosolve, Genzyme, Eli Lilly, Pfizer, Nordic Bioscience, Wyeth, and Pozen. Other co-authors reported relationships with additional firms including Zosano, UCB Pharma, Genentech, Roche, Ortho-McNeil-Janssen, Procter & Gamble, and Bristol-Myers Squibb.

Jordan reported relationships with Endo, Stryker, Novartis, and Algynomics.

McAlindon reported no potential conflicts of interest.

ACR: Weight Loss Helps Stave Off OA Disability

By John Gever, Senior Editor, MedPage Today
Published: October 22, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
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PHILADELPHIA -- Losing weight can prevent osteoarthritis of the knee or improve function for those who already have it, researchers said here.

Individuals who lost weight in a long-term observational study were at nearly 30% lower risk of developing knee osteoarthritis (HR 0.71, 95% CI 0.49 to 1.01), Lauren Abbate, a third-year medical student at the University of North Carolina in Chapel Hill, reported at the American College of Rheumatology meeting.

And a separate study of patients already diagnosed with the condition showed that weight loss was associated with improvements in physical function and walking speed, said Danuta Bujak, PhD, of the University of Maryland's medical school in Baltimore.
Action Points
Explain to interested patients that body weight is believed to be related both to incidence of knee osteoarthritis and the severity of symptoms. These studies appear to confirm those relationships.


Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
But both studies also contained cautionary messages about weight. Abbate said that participants in the North Carolina study whose weight remained steady fared no better than those who gained weight.
Bujak, meanwhile, noted that the degree of weight loss and the amount of symptom improvement in her study were both small. Moreover, weight loss had no impact on pain severity, she said.

Bujak's study drew on data from the Osteoarthritis Initiative, an ongoing observational study with nearly 5,000 current participants, intended to last four years. She and her colleagues analyzed data from 1,109 participants with radiographically confirmed knee osteoarthritis for whom two years of follow-up data were available.

The participants were 61 years old on average at baseline, and 57% were women. Their mean body mass index was 30.2 at baseline and mean weight was 86.1 kg (190 lbs).

Participants on average lost weight during follow-up, though not much -- a total of 0.6 kg (1.3 lbs).

Small but significant improvements were found in total scores on the Western Ontario McMaster Osteoarthritis Index (WOMAC) and in its physical function subscale, the Physical Activity Scale in the Elderly (PASE), and 20-meter walk speed, after adjusting for age, sex, race, and use of pain medications:

Total WOMAC score: 24.8 baseline, improvement 0.148
WOMAC physical function: 16.9 baseline, improvement 0.116
PASE: 157.4 baseline, improvement 0.924
20-meter walk speed: 1.27 m/sec baseline, improvement 0.02
However, Bujak said there was no improvement in WOMAC pain scores with weight loss after the adjustments.

She also said that when participants were grouped into tertiles of weight loss, there was no relationship between the amount of weight lost and the amount of improvement on the main outcome measures.

"We are hoping over time to see effects in the weight change tertiles" as longer follow-up data become available, Bujak said.

Abbate and colleagues analyzed data from the Johnston County (N.C.) Osteoarthritis Project, another prospective observational study, in which participants were healthy at baseline. They are being followed to identify factors potentially associated with later development of osteoarthritis.

The 1,480 participants included in the study were initially enrolled from 1990 to 1998, and reexamined from 1999 to 2003 for a median follow-up time of 5.9 years.

Incident knee osteoarthritis was diagnosed radiographically, defined as progression from Kellgren-Lawrence grade of zero or one at baseline to at least two at follow-up.

Of a total of 2,788 knees examined, 415 became osteoarthritic during follow-up, Abbate said.

Some 31% of participants gained significant weight (at least 5% from baseline), 33% had stable weight (within 3% of baseline weight), and 17% lost at least 5% of body weight during follow-up.

With the incidence of osteoarthritis among those gaining weight as the reference, the hazard ratio for osteoarthritis among those with stable weight was 1.02 (95% CI 0.77 to 1.35).

Although the 29% reduction in risk seen with weight loss did not reach statistical significance, Abbate said the findings generally confirmed earlier data suggesting that it's an effective strategy for overweight individuals to avoid developing knee osteoarthritis.

Bujak voiced a similar conclusion from her data, although she cautioned that the small average weight change seen in the Osteoarthritis Initiative cohort was a significant limitation.

The Osteoarthritis Initiative is funded by the National Institutes of Health. No additional funding for the data analysis was reported.

The Johnston County Osteoarthritis Project is funded by the CDC. No additional funding for the data analysis was reported.

Bujack reported no conflicts of interest. Co-authors on the study reported relationships with Bayer, Bioiberica, Combinatorx, Endo, Ferring, Genzyme, Merck, NicOx, Novartis, and Pozen.

Abbate and colleagues reported no relevant conflicts.


Primary source: Arthritis & Rheumatism
Source reference:
Abbate L, et al "The relationship between weight maintenance and incident radiographic knee osteoarthritis: the Johnston County Osteoarthritis Project" Arthritis Rheum 2009; 60: S235.

Additional source: Arthritis & Rheumatism
Source reference:
Bujak D, et al "Relationship of weight and weight change with knee pain and function in persons with symptomatic radiographic knee osteoarthritis: Two-year data from the Osteoarthritis Initiative" Arthritis Rheum 2009; 60: S206.