Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain.

Abstract

OBJECTIVE:

To evaluate whether subjects with knee or hip osteoarthritis (OA) pain on non-steroidal anti-inflammatory drugs (NSAIDs) received greater benefit when tanezumab monotherapy replaced or was coadministered with NSAIDs.

METHODS:

Subjects (N=2700) received intravenous tanezumab (5 or 10 mg) or placebo every 8 weeks with or without oral naproxen 500 mg twice daily or celecoxib 100 mg twice daily. Efficacy was assessed as change from baseline to week 16 in three co-primary endpoints: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function and Patient's Global Assessment (PGA) of OA. Safety assessments included adverse events, physical and neurological examinations, laboratory tests and vital signs.

RESULTS:

Although all tanezumab treatments provided significant improvements in WOMAC Pain and Physical Function over either NSAID alone, only tanezumab+NSAIDs were significant versus NSAIDs with PGA and met the prespecified definition of superiority. Combination treatment did not substantially improve pain or function over tanezumab monotherapy. Adverse event frequency was higher with tanezumab than with NSAIDs and highest with combination therapy. Higher incidence of all-cause total joint replacements occurred with tanezumab+NSAID versus tanezumab monotherapy or NSAIDs. Rapidly progressive OA incidence was significantly greater versus NSAID in all tanezumab groups except tanezumab 5 mg monotherapy.

CONCLUSIONS:

Subjects receiving partial symptomatic relief of OA pain with NSAIDs may receive greater benefit with tanezumab monotherapy. While only coadministration of tanezumab with NSAIDs met the definition of superiority, combination treatment did not provide important benefits over tanezumab monotherapy; small differences in efficacy were negated by treatment-limiting or irreversible safety outcomes.

TRIAL REGISTRATION NUMBER:

NCT00809354.

• Authors: Thomas J Schnitzer, Evan F Ekman, Egilius L H Spierings, H Scott Greenberg, Michael D Smith, Mark T Brown, Christine R West, Kenneth M Verburg
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 74 Issue 6 Pg. 1202-11 (Jun 2015) ISSN: 1468-2060 [Electronic] England
• PMID: 24625625 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antibodies, Monoclonal, Humanized
• Pyrazoles
• Sulfonamides
• Naproxen
• tanezumab
• Celecoxib

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Arthralgia (drug therapy, etiology)
• Arthroplasty, Replacement (statistics & numerical data)
• Celecoxib
• Double-Blind Method
• Drug Therapy, Combination
• Edema (chemically induced)
• Female
• Humans
• Hypesthesia (chemically induced)
• Male
• Middle Aged
• Naproxen (therapeutic use)
• Osteoarthritis, Hip (complications, drug therapy)
• Osteoarthritis, Knee (complications, drug therapy)
• Paresthesia (chemically induced)
• Pyrazoles (therapeutic use)
• Sulfonamides (therapeutic use)
• Treatment Outcome