Tanezumab for the treatment of pain from osteoarthritis of the knee

Nancy E Lane, Thomas J. Schnitzer, Charles A. Birbara, Masoud Mokhtarani, David L. Shelton, Mike D. Smith, Mark T. Brown

Research output: Contribution to journalArticle

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Abstract

Background: Increased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor. Methods: We randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and Mc-Master Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT - OARSI); and safety. Results: When averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT - OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%). Conclusions: In this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee.

Original languageEnglish (US)
Pages (from-to)1521-1531
Number of pages11
JournalNew England Journal of Medicine
Volume363
Issue number16
DOIs
StatePublished - Oct 14 2010

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Knee Osteoarthritis
Pain
Placebos
Therapeutics
Nerve Growth Factor
Walking
Knee
Safety
Antibodies, Monoclonal, Humanized
tanezumab
Paresthesia
Arthralgia
Rheumatology
Ontario
Respiratory Tract Infections
Osteoarthritis
Headache
Analgesics
Body Weight
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lane, N. E., Schnitzer, T. J., Birbara, C. A., Mokhtarani, M., Shelton, D. L., Smith, M. D., & Brown, M. T. (2010). Tanezumab for the treatment of pain from osteoarthritis of the knee. New England Journal of Medicine, 363(16), 1521-1531. https://doi.org/10.1056/NEJMoa0901510

Tanezumab for the treatment of pain from osteoarthritis of the knee. / Lane, Nancy E; Schnitzer, Thomas J.; Birbara, Charles A.; Mokhtarani, Masoud; Shelton, David L.; Smith, Mike D.; Brown, Mark T.

In: New England Journal of Medicine, Vol. 363, No. 16, 14.10.2010, p. 1521-1531.

Research output: Contribution to journalArticle

Lane, NE, Schnitzer, TJ, Birbara, CA, Mokhtarani, M, Shelton, DL, Smith, MD & Brown, MT 2010, 'Tanezumab for the treatment of pain from osteoarthritis of the knee', New England Journal of Medicine, vol. 363, no. 16, pp. 1521-1531. https://doi.org/10.1056/NEJMoa0901510
Lane NE, Schnitzer TJ, Birbara CA, Mokhtarani M, Shelton DL, Smith MD et al. Tanezumab for the treatment of pain from osteoarthritis of the knee. New England Journal of Medicine. 2010 Oct 14;363(16):1521-1531. https://doi.org/10.1056/NEJMoa0901510
Lane, Nancy E ; Schnitzer, Thomas J. ; Birbara, Charles A. ; Mokhtarani, Masoud ; Shelton, David L. ; Smith, Mike D. ; Brown, Mark T. / Tanezumab for the treatment of pain from osteoarthritis of the knee. In: New England Journal of Medicine. 2010 ; Vol. 363, No. 16. pp. 1521-1531.
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AU - Lane, Nancy E

AU - Schnitzer, Thomas J.

AU - Birbara, Charles A.

AU - Mokhtarani, Masoud

AU - Shelton, David L.

AU - Smith, Mike D.

AU - Brown, Mark T.

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N2 - Background: Increased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor. Methods: We randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and Mc-Master Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT - OARSI); and safety. Results: When averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT - OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%). Conclusions: In this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee.

AB - Background: Increased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor. Methods: We randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and Mc-Master Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT - OARSI); and safety. Results: When averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT - OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%). Conclusions: In this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee.

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