Safety and efficacy of subcutaneous tanezumab in patients with knee or hip osteoarthritis
Authors Birbara C, Dabezies JR EJ, Burr AM, Fountaine RJ, Smith MD, Brown MT, West CR, Arends RH, Verburg KM
Received 19 April 2017
Accepted for publication 14 September 2017
Published 8 January 2018 Volume 2018:11 Pages 151—164
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Katherine Hanlon
Charles Birbara,1 Eugene J Dabezies JR,2 Aimee M Burr,3 Robert J Fountaine,3 Michael D Smith,3 Mark T Brown,3 Christine R West,3 Rosalin H Arends,3 Kenneth M Verburg3
1Department of Medicine, University of Massachusetts School of Medicine, Worcester, MA, 2Pensacola Research Consultants, Pensacola, FL, 3Clinical Development and Operations Business Unit, Pfizer Inc., Groton, CT, USA
Background/objective: The objective of this study was to investigate the safety and efficacy of subcutaneous (SC) and intravenous (IV) tanezumab administration in osteoarthritis (OA) patients.
Materials and methods: Study 1027 (NCT01089725), a placebo-controlled trial, evaluated the efficacy of SC tanezumab (ie, 2.5, 5, and 10 mg) and the therapeutic equivalence of 10 mg tanezumab given subcutaneously versus intravenously every 8 weeks in the symptomatic treatment of OA. Coprimary endpoints were: change from baseline in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) Pain and Physical Function indices, and Patient’s Global Assessment (PGA) of OA. Study 1043 (NCT00994890) was a long-term, noncontrolled safety study of tanezumab (ie, 2.5, 5, and 10 mg) subcutaneously administered every 8 weeks. Both studies were discontinued prematurely due to a US Food and Drug Administration partial clinical hold.
Results: Due to the clinical hold, Study 1027 was underpowered, and no statistical analyses were performed. Mean (standard error [SE]) change from baseline to week 8 in WOMAC Pain in tanezumab groups ranged from −3.59 (0.26) to −3.89 (0.32), versus −2.74 (0.25) with placebo. Mean (SE) change from baseline to week 8 in WOMAC Physical Function ranged from −3.13 (0.25) to −3.51 (0.28) with tanezumab and was −2.26 (0.24) with placebo. PGA mean (SE) change from baseline to week 8 ranged from −0.90 (0.11) to −1.08 (0.12) with tanezumab and was −0.78 (0.10) with placebo. Similar effectiveness was associated with tanezumab in Study 1043. Few patients in either study (1.4%–5.2%) discontinued due to adverse events. Five patients required total joint replacements in Study 1027 (placebo, n=2 [2.8%]; tanezumab 2.5 mg, n=3 [4.1%]) and 34 patients in Study 1043 (tanezumab 2.5 mg, n=11 [4.8%]; tanezumab 5 mg, n=8 [3.6%]; tanezumab 10 mg, n=15 [6.6%]).
Conclusion: Preliminary results show similar efficacy and safety for both SC and IV administration of tanezumab based on the direct comparisons reported here and indirect comparisons with published results, confirming pharmacokinetic/pharmacodynamic modeling predictions.
Keywords: tanezumab, subcutaneous, osteoarthritis, efficacy, safety
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