A clinical trial of a novel drug known as tanezumab has shown that treatment once every eight weeks significantly reduces pain in patients with knee osteoarthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.

Osteoarthritis is the most common joint disease affecting middle-age and older people. It is characterized by progressive damage to the joint cartilage—the slippery material at the end of long bones—and causes changes in the structures around the joint. These changes can include fluid accumulation, bony overgrowth, and loosening and weakness of muscles and tendons, all of which may limit movement and cause pain and swelling.

The weight-bearing joints including the knees, hips and spine are most often affected by osteoarthritis. Osteoarthritis in the knee and hip areas can cause chronic pain or discomfort during standing or walking.

Researchers recently set out to determine if tanezumab, a humanized monoclonal antibody specific for nerve growth factor, is effective in relieving the pain of those with moderate to severe knee OA. They followed 444 men and women who ranged in age from 40 to 78 and had moderate to severe pain associated with their knee OA. Patients enrolled had not had successful control of their pain by nonsteroidal anti-inflammatory drugs, such as ibuprofen or naproxen, or were considered candidates for more invasive treatments such as total joint replacement.

The 444 patients enrolled in this 16 week study were treated with either tanezumab or placebo. Tanezumab was intravenously administered at ten, 25, 50, 100, or 200 µg/kg on days one and 56 of the study. Researchers measured effectiveness by evaluating knee pain with walking and patient global assessment of response to the treatment, as well as other outcome measures, including stiffness and physical function.

Researchers found that tanezumab treatment significantly improved knee pain and the patients’ overall assessments of their condition when compared with placebo over the time of the study. At weeks 12 and 16, researchers noted a significant improvement in the secondary outcome measures, including pain, physical function and stiffness.

Treatment related adverse events occurred in 21 percent of patients receiving tanezumab and in 8 percent of those receiving placebo. Among the patients receiving tanezumab, the most common adverse events among patients receiving tanezumab were headache, upper respiratory tract infection and abnormal tingling sensations.

“Effective treatment to relieve pain in patients with osteoarthritis is an unmet medical need,” says Nancy E. Lane, MD; director and endowed professor, University of California at Davis Medical Center, Aging Center, Medicine and Rheumatology, Sacramento, Calif. “Recent work has found that nerve growth factors are synthesized at sites of inflammation and appear to accentuate pain. Treatment with a monoclonal antibody against nerve growth factor, tanezomab, was very effective in reducing knee pain and improving physical function in patients with moderate to severe knee OA. Therefore, inhibition of nerve growth factor may provide a new type of therapy to reduce pain in OA and possibly other pain states,” explains Dr. Lane. Phase III studies are now being initiated to further define the effectiveness of this medication.

Patients should talk to their rheumatologists to determine their best course of treatment.

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.

Editor’s Notes: Dr. Lane will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 4:30 – 4:45 PM on Tuesday, October 28, in Room 303. Dr. Lane will be available for media questions and briefing at 1:30 PM on Sunday, October 26 in the on-site press conference room, 114.

Presentation Number: 1989

Tanezumab Relieves Moderate to Severe Pain Due to Osteoarthritis (OA) of the Knee: A Phase 2 Trial

Nancy E. Lane1, Thomas J. Schnitzer2, Michael D. Smith3, Mark T. Brown3. 1University of California at Davis Medical Center, Sacramento, CA; 2Northwestern University, Chicago, IL; 3Pfizer Inc, New London, CT

Purpose: To evaluate the analgesic efficacy and safety of tanezumab, a humanized monoclonal antibody specific for nerve growth factor, in patients with moderate to severe knee pain due to OA.

Methods: A total of 450 men and women aged 40-78 years who had previously failed NSAIDs or were candidates for invasive interventions such as total joint replacement were enrolled in a 16-week, randomized, placebo-controlled, parallel-arm, double-blind, multiple-dose study. Baseline knee pain with walking was required to be ≥50 and ≤90 on a 0-100 mm Visual Analog Scale. Tanezumab was administered intravenously at 10, 25, 50, 100 and 200 μg/kg on Day 1 and Day 56. The primary efficacy measures were knee pain with walking and patient global assessment of response to therapy. Prespecified secondary endpoints included Western Ontario and McMaster Universities index (WOMAC) Physical Function, Pain, and Stiffness scores (assessed at baseline and every 2 weeks through Week 16), the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder index and the incidence of adverse events (AEs).

Results: Treated patients (n=444) were 41% male, 88% white, with a mean (±SD) age of 58.7±8.0 yrs; the median time since diagnosis of OA was 5.1 yrs. Tanezumab treatment improved knee pain and patient global assessment (P

<0.005, primary endpoints) compared with placebo over the 16 weeks. At Weeks 12 and 16, significant improvement in WOMAC Physical Function, Pain, and Stiffness scores and more OMERACT-OARSI responders were noted in all tanezumab treatment groups vs placebo (Table). Treatment-related AEs were reported in 21% of patients receiving tanezumab and 8% of those receiving placebo. Across the tanezumab groups, the most common AEs were headache (8.9%), upper respiratory tract infection (7.3%), and paresthesia (6.8%).

Conclusions: Administration of tanezumab once every 8 weeks resulted in a significant benefit for patients with painful knee OA, as assessed by OMERACT-OARSI responder index and WOMAC physical function, pain and stiffness scores.

Disclosure Block: N.E. Lane, Rinat/Pfizer Inc, 2; T.J. Schnitzer, Genzyme, 2; Lilly, 2; Novartis, 2; Pfizer, 2; Wyeth, 2; GSK, 5; Merck, 5; NicOx, 5; Novartis, 5; M.D. Smith, Pfizer, 3; M.T. Brown, Pfizer, 3.

Source: American College of Rheumatology (ACR)