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Long-Term Safety and Efficacy of Subcutaneous Tanezumab Versus Nonsteroidal Antiinflammatory Drugs for Hip or Knee Osteoarthritis: A Randomized Trial
, Corresponding Author University of Maryland School of Medicine, Baltimore Address correspondence to Marc C. Hochberg, MD, MPH, University of Maryland School of Medicine, 10 South Pine Street, MSTF 8-34, Baltimore, MD 21201. Email: mhochber@som.umaryland.edu. Search for more papers by this author Hospital for Special Surgery, New York, New York Search for more papers by this author Northwestern University Feinberg School of Medicine, Chicago, Illinois Search for more papers by this author Boston University School of Medicine, Boston, Massachusetts Search for more papers by this author Arthritis Research UK Pain Centre, NIHR Nottingham Biomedical Research Centre, and University of Nottingham, Nottingham, UK Search for more papers by this author Progressive Medical Research, Port Orange, Florida Search for more papers by this author Nakajo Orthopaedic Clinic, Miyagi, Japan Search for more papers by this author Pfizer, Inc., Morrisville, North Carolina Search for more papers by this author
First published: 03 February 2021
Citations: 7
ClinicalTrials.gov identifier: NCT02528188.
Supported by Pfizer and Eli Lilly.
1Marc C. Hochberg, MD, MPH: University of Maryland School of Medicine, Baltimore; 2John A. Carrino, MD, MPH: Hospital for Special Surgery, New York, New York; 3Thomas J. Schnitzer, MD, PhD: Northwestern University Feinberg School of Medicine, Chicago, Illinois; 4Ali Guermazi, MD, PhD: Boston University School of Medicine, Boston, Massachusetts; 5David A. Walsh, MBBS, PhD: Arthritis Research UK Pain Centre, NIHR Nottingham Biomedical Research Centre, and University of Nottingham, Nottingham, UK; 6Alexander White, MD: Progressive Medical Research, Port Orange, Florida; 7Satoru Nakajo, MD: Nakajo Orthopaedic Clinic, Miyagi, Japan; 8Robert J. Fountaine, PharmD, Anne Hickman, DVM, PhD, Mark T. Brown, MD, Christine R. West, PhD, Kenneth M. Verburg, PhD: Pfizer Inc., Groton, Connecticut; 9Glenn Pixton, MS: Pfizer, Inc., Morrisville, North Carolina; 10Lars Viktrup, MD, PhD: Eli Lilly, Indianapolis, Indiana.
Dr. Hochberg has received consulting fees from Bone Therapeutics, Bristol Myers Squibb, Eli Lilly, EMD Serono, Novartis, Pfizer, Regenosine, Samumed LLC, Theralogix LLC, Kolon TissueGene Inc., TLC Biopharmaceuticals, and Zynerba; is a member of the Data Safety Monitoring Committee for clinical trials conducted by Covance, Galápagos, ICON plc, IQVIA, and SunPharma (less than $10,000 each); has received royalties from Elsevier (Editor, Rheumatology 7th edition and Editor-in-Chief, Seminars in Arthritis and Rheumatism) and UpToDate; and owns stock or stock options in BriOri Biotech and Theralogix. Dr. Carrino has received consulting fees from Covera Health, Image Analysis Group, Image Biopsy Lab, Pfizer, and Simplify Medical (less than $10,000 each). Dr. Schnitzer has received grants, personal fees, and nonfinancial support from AbbVie, Kolon TissueGene, Pfizer, and Regeneron; personal fees from Astellas, Calibr, Sanofi, and Vertex; grants and personal fees from Flexion; personal fees and non-financial support from Aptinyx and GlaxoSmithKline; and grants from Galapagos and Grünenthal. Dr. Guermazi has received consulting fees from AstraZeneca, Galápagos, Merck Serono, Pfizer, Kolon TissueGene, and Roche, and owns stock or stock options in Boston Imaging Core Lab. Dr. Walsh has received consulting fees, speaking fees, and/or honoraria from Pfizer and GlaxoSmithKline (less than $10,000 each). Drs. Fountaine, Hickman, Brown, West, and Verburg and Mr. Pixton own stock or stock options in Pfizer. Dr. Viktrup owns stock or stock options in Eli Lilly. No other disclosures relevant to this article were reported.
Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual deidentified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices 1) for indications that have been approved in the United States and/or Europe or 2) in programs that have been terminated (i.e., development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The deidentified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.
Abstract
Objective
To assess the long-term safety and 16-week efficacy of subcutaneous tanezumab in patients with hip or knee osteoarthritis (OA).
Methods
This was a phase III randomized, double-blind, active treatment–controlled (using nonsteroidal antiinflammatory drugs [NSAIDs] as the active treatment control) safety trial of tanezumab (56-week treatment/24-week posttreatment follow-up) in adults who were receiving stable-dose NSAID therapy at the time of screening and who had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores of ≥5; patient global assessment (PtGA) of OA of fair, poor, or very poor; history of inadequate pain relief with standard analgesics; and no history or radiographic evidence of prespecified bone/joint conditions beyond OA. Patients received oral naproxen, celecoxib, or diclofenac twice daily (NSAID group; n = 996) or tanezumab 2.5 mg (n = 1,002) or 5 mg (n = 998) subcutaneously every 8 weeks. Coprimary efficacy end points at week 16 were changes in WOMAC pain and physical function scores and changes in PtGA. The primary joint safety end point over 80 weeks comprised adjudicated rapidly progressive OA type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture. Mean values, least squares mean values, and least squares mean differences between groups (with 95% confidence intervals [95% CIs]) were calculated.
Results
Of 3,021 randomized patients, 2,996 received ≥1 treatment dose. Adverse events (AEs) were similar between patients treated with tanezumab 2.5 mg and those treated with NSAIDs, and were more prevalent in those treated with tanezumab 5 mg. Composite joint safety events were significantly more prevalent with tanezumab 2.5 mg and tanezumab 5 mg than with NSAIDs (observation time–adjusted rate/1,000 patient-years 38.3 [95% CI 28.0, 52.5] and 71.5 [95% CI 56.7, 90.2], respectively, versus 14.8 [95% CI 8.9, 24.6]; P = 0.001 for tanezumab 2.5 mg versus NSAIDs; P < 0.001 for tanezumab 5 mg versus NSAIDs). Tanezumab 5 mg significantly improved pain and physical function but did not improve PtGA at week 16 when compared to NSAIDs; corresponding differences between the tanezumab 2.5 mg and NSAID groups were not statistically significant.
Conclusion
In patients previously receiving a stable dose of NSAIDs, tanezumab administered subcutaneously resulted in more joint safety events than continued NSAIDs, with differences being dose dependent. Pain and physical function improved with both doses of tanezumab compared to NSAIDs, reaching statistical significance with tanezumab 5 mg at 16 weeks.
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Source: https://onlinelibrary.wiley.com/doi/abs/10.1002/art.41674
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