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Among patients with moderate to severe osteoarthritis of the knee or hip and inadequate treatment response to standard analgesics, what is the effect of subcutaneous tanezumab on joint pain, physical function, and patient global assessment of osteoarthritis?
In this randomized clinical trial that enrolled 698 patients, subcutaneous tanezumab administered with fixed doses at 8-week intervals or with a forced titration at week 8, compared with placebo, resulted in statistically significant improvements in joint pain, physical function, and patient global assessment of osteoarthritis over 16 weeks, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements.
Further research is needed to determine the clinical importance of these efficacy and adverse event findings with regard to use of tanezumab for treatment of osteoarthritis.
Patients with osteoarthritis (OA) may remain symptomatic with traditional OA treatments.
To assess 2 subcutaneous tanezumab dosing regimens for OA.
Design, Setting, and Participants
A randomized, double-blind, multicenter trial from January 2016 to May 14, 2018 (last patient visit). Patients enrolled were 18 years or older with hip or knee OA, inadequate response to OA analgesics, and no radiographic evidence of prespecified joint safety conditions.
Patients received by subcutaneous administration either tanezumab, 2.5 mg, at day 1 and week 8 (n = 231); tanezumab, 2.5 mg at day 1 and 5 mg at week 8 (ie, tanezumab, 2.5/5 mg; n = 233); or placebo at day 1 and week 8 (n = 232).
Main Outcomes and Measures
Co–primary end points were change from baseline to week 16 in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain (0-10, no to extreme pain), WOMAC Physical Function (0-10, no to extreme difficulty), and patient global assessment of osteoarthritis (PGA-OA) (1-5, very good to very poor) scores.
Among 698 patients randomized, 696 received 1 or more treatment doses (mean [SD] age, 60.8 [9.6] years; 65.1% women), and 582 (83.6%) completed the trial. From baseline to 16 weeks, mean WOMAC Pain scores decreased from 7.1 to 3.6 in the tanezumab, 2.5 mg, group; 7.3 to 3.6 in the tanezumab, 2.5/5 mg, group; and 7.3 to 4.4 in the placebo group (least squares mean differences [95% CI] vs placebo were −0.60 [−1.07 to −0.13; P = .01] for tanezumab, 2.5 mg, and −0.73 [−1.20 to −0.26; P = .002] for tanezumab, 2.5/5 mg). Mean WOMAC Physical Function scores decreased from 7.2 to 3.7 in the 2.5-mg group, 7.4 to 3.6 in the 2.5/5-mg group, and 7.4 to 4.5 with placebo (differences vs placebo, −0.66 [−1.14 to −0.19; P = .007] for tanezumab, 2.5 mg, and −0.89 [−1.37 to −0.42; P < .001] for tanezumab, 2.5/5 mg). Mean PGA-OA scores decreased from 3.4 to 2.4 in the 2.5-mg group, 3.5 to 2.4 in the 2.5/5-mg group, and 3.5 to 2.7 with placebo (differences vs placebo, −0.22 [−0.39 to −0.05; P = .01] for tanezumab, 2.5 mg, and −0.25 [−0.41 to −0.08; P = .004] for tanezumab, 2.5/5 mg). Rapidly progressive OA occurred only in tanezumab-treated patients (2.5 mg: n = 5, 2.2%; 2.5/5 mg: n = 1, 0.4%). The incidence of total joint replacements was 8 (3.5%), 16 (6.9%), and 4 (1.7%) in the tanezumab, 2.5 mg; tanezumab, 2.5/5 mg; and placebo groups, respectively.
Conclusions and Relevance
Among patients with moderate to severe OA of the knee or hip and inadequate response to standard analgesics, tanezumab, compared with placebo, resulted in statistically significant improvements in scores assessing pain and physical function, and in PGA-OA, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements. Further research is needed to determine the clinical importance of these efficacy and adverse event findings.
ClinicalTrials.gov Identifier: NCT02697773
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Corresponding Author: Thomas J. Schnitzer, MD, PhD, Feinberg School of Medicine, Northwestern University, 710 N Lake Shore Dr, Abbot Hall, Ste 1020, Chicago, IL 60611 (firstname.lastname@example.org).
Accepted for Publication: May 22, 2019.
Author Contributions: Dr Schnitzer had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Pixton, Viktrup, Davignon, Brown, West, Verburg.
Acquisition, analysis, or interpretation of data: Schnitzer, Easton, Pang, Levinson, Pixton, Viktrup, Davignon, Brown, West.
Drafting of the manuscript: Easton, Levinson, Pixton, Viktrup, Brown, West, Verburg.
Critical revision of the manuscript for important intellectual content: Schnitzer, Easton, Pang, Pixton, Viktrup, Davignon, Brown, West.
Statistical analysis: Pixton.
Administrative, technical, or material support: Easton, Levinson.
Supervision: Easton, Pang, Viktrup, Davignon, Brown, West, Verburg.
Conflict of Interest Disclosures: Dr Schnitzer reported receiving nonfinancial support from Pfizer during the conduct of the study and grants, personal fees, and nonfinancial support from Pfizer, Regeneron, AbbVie, and Kolon TissueGene; personal fees from Vertex, Sanofi, Astellas, and Calibr; grants and personal fees from Flexion; personal fees and nonfinancial support from GlaxoSmithKline and Aptinyx; and grants from Galapagos and Grunenthal outside the submitted work. Dr Schnitzer also reported performing clinical research for Pfizer Inc and Eli Lilly and Company and has received consulting fees from Pfizer Inc and Eli Lilly and Company. Dr Easton reported receiving compensation for participation in multiple Pfizer-sponsored clinical trials. Dr Pang reported receiving consulting fees from Pfizer Inc. Dr Levinson reported receiving grants from Pfizer during the conduct of the study and grants from Amgen, Regeneron, and AbbVie outside the submitted work. Mr Pixton and Drs Davignon, Brown, Verburg, and West are employees of Pfizer Inc and own stock. Dr Viktrup is an employee of Eli Lilly and Company. Drs Brown and West reported having tanezumab method of treatment patents pending. No other disclosures were reported.
Funding/Support: The study was sponsored by Pfizer Inc and Eli Lilly and Company.
Role of the Funder/Sponsor: Pfizer Inc and Eli Lily and Company contributed to the study design; Pfizer contributed to the management and collection of data. In their role as authors, employees of Pfizer and Eli Lilly were involved in the interpretation of data, preparation, review, and approval of the manuscript and the decision to submit for publication, along with their co-authors. The study sponsors approved the manuscript from an intellectual property perspective but had no right to veto the publication.
Additional Contributions: Editorial support was provided by Shannon Buckley, PhD, and Matt Soulsby, PhD, CMPP, of Engage Scientific Solutions and were funded by Pfizer and Eli Lilly and Company. We thank the central imaging readers: Ali Guermazi, MD, PhD, and Frank Roemer, MD, from Boston Imaging Core Lab, Boston, Massachusetts. We also thank the adjudication committee members for blinded adjudication of joint safety events: David Hungerford, MD (Johns Hopkins University), John Carrino, MD, MPH (Hospital for Special Surgery), Timothy McAlindon, MD, MPH (Tufts Medical Center), Eric Vignon, MD (Université Claude Bernard Lyon 1), and Edward McCarthy, MD (Johns Hopkins University). Central readers and adjudication committee members received financial compensation for these study activities.
Data Sharing Statement: See Supplement 4.
Additional Information: Pfizer Inc, in collaboration with Eli Lilly and Company, is the manufacturer of tanezumab, which is being investigated for the treatment of chronic pain.
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