Abstract
Introduction: Combining measures of key core domains (especially pain and function) into a composite endpoint that requires each patient to meet a threshold of improvement for each domain provides information on multiple aspects of osteoarthritis within individual patients. This pooled analysis of two phase 3 studies (NCT02697773, NCT02709486) explored single and composite endpoints for assessing within-patient improvement in knee or hip osteoarthritis symptoms following subcutaneous administration of tanezumab or placebo. Methods: Endpoints at week 16 included proportions of responders (≥ 30% improvement) in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Physical Function, WOMAC Pain/Function composite, and weekly average pain; and patient acceptable symptom state (PASS) composite responders, minimal clinically important improvement (MCII) composite responders, Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responders, and sustained weekly average pain responders. Results: Pooled population comprised 1545 patients. Of patients who had a ≥ 30% improvement in WOMAC Pain and/or WOMAC Physical Function, 88.5% were WOMAC Pain/Function composite responders, 7.0% were WOMAC Pain (but not Function) responders, and 4.4% were WOMAC Function (but not Pain) responders. Of weekly average pain responders, 43.1% were PASS composite responders. Odds ratios (tanezumab 2.5 mg and 5 mg groups, respectively, vs placebo) were 1.75 and 1.86 (WOMAC Pain/Function composite responders), 1.41 and 1.65 (weekly average pain responders), 1.60 and 1.73 (PASS composite responders), 1.52 and 1.68 (MCII composite responders), 1.75 and 1.88 (OMERACT-OARSI responders), and 1.85 and 1.48 (sustained weekly average pain responders). Subgroup analyses suggested a greater magnitude of effect for patients with a knee index joint compared with hip on some endpoints. Conclusion: Responders on single pain endpoints were in many cases also responders on function or composite endpoints. Separation of tanezumab from placebo was similar and consistent across single and composite endpoints.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1759-1774 |
| Number of pages | 16 |
| Journal | Rheumatology and Therapy |
| Volume | 8 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 2021 |
Funding
Medical writing support was provided by Kim Russell, PhD, of Engage Scientific Solutions (Horsham, UK) and was funded by Pfizer and Eli Lilly and Company. The study was sponsored by Pfizer and Eli Lilly and Company. Publication fees (expenses to the journal for Rapid Service and Open Access) were funded by Pfizer and Eli Lilly and Company. Pfizer is the manufacturer of tanezumab, which is being investigated for the treatment of patients with chronic pain. Manuscript authors from Pfizer contributed to the study design; data collection, management, and interpretation of data; and the preparation, review, and approval of the manuscript. Manuscript authors from Eli Lilly and Company contributed to the study design; interpretation of data; and the preparation, review, and approval of the manuscript. Philip G. Conaghan is supported in part through the United Kingdom National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The study was sponsored by Pfizer and Eli Lilly and Company. Publication fees (expenses to the journal for Rapid Service and Open Access) were funded by Pfizer and Eli Lilly and Company. Pfizer is the manufacturer of tanezumab, which is being investigated for the treatment of patients with chronic pain. Manuscript authors from Pfizer contributed to the study design; data collection, management, and interpretation of data; and the preparation, review, and approval of the manuscript. Manuscript authors from Eli Lilly and Company contributed to the study design; interpretation of data; and the preparation, review, and approval of the manuscript. Medical writing support was provided by Kim Russell, PhD, of Engage Scientific Solutions (Horsham, UK) and was funded by Pfizer and Eli Lilly and Company. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. All authors contributed to the conception or design of the study. Ruoyong Yang, Isabelle Davignon, Christine R. West, and Kenneth M. Verburg contributed to the acquisition of data. All authors contributed to the analysis or interpretation of data. All authors contributed to drafting the manuscript and revising it critically for important intellectual content. All authors approved the final version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Thomas J. Schnitzer reports clinical research study support (Pfizer, Lilly, Regeneron, Galapagos, Taiwan Liposome Corporation, Anika Therapeutics) and fees for consultancy/advisory boards (Pfizer, Lilly, GSK, AstraZeneca, Galapagos, Merck). Francis Berenbaum reports grant/research support (TRB Chemedica) and fees for consultancy (Boehringer, Bone Therapeutics, CellProthera, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, 4P Pharma, 4Moving Biotech). Philip G. Conaghan reports fees for speaker?s bureaus (AbbVie, Novartis) and consultancy (AstraZeneca, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer). Robert H. Dworkin has received in the past 5?years research grants and contracts (US Food and Drug Administration and the US National Institutes of Health), and compensation for serving on advisory boards or consulting on clinical trial methods (Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Cardialen, Celgene, Centrexion, Chromocell, Clexio, Collegium, Concert, Confo, Decibel, Dong-A, Editas, Eli Lilly, Ethismos [equity], Eupraxia, Glenmark, Grace, Hope, Immune, Lotus, Mainstay, Merck, Neumentum, Neurana, NeuroBo, Novaremed, Novartis, Olatec, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy [also equity], Relmada, Sanifit, Scilex, Semnur, SIMR Bio, SK Life Sciences, Sollis, SPRIM, Teva, Theranexus, Trevena, Vertex, and Vizuri). Davide Gatti reports fees for speaker?s bureaus (Celgene, Neopharmed-Gentili, Eli Lilly, UCB) and consultancy (Abiogen, MSD Italia, Pfizer). Ruoyong Yang, Isabelle Davignon, Christine R. West, and Kenneth M. Verburg are employees of Pfizer with stock and/or stock options. Lars Viktrup is an employee of Eli Lilly and Company and owns stock in Lilly. Some of these data were presented at American College of Rheumatology (ACR) Convergence, November 5?9, 2020. The study protocols were approved by the appropriate institutional review board or independent ethics committee at each participating investigational center (main IRB for Study?1: Schulman Associates IRB/Advarra, Ohio, United States; for Study?2, see supplementary Appendix 1). All patients provided written informed consent prior to entering the studies. The studies were conducted in compliance with the Declaration of Helsinki and International Conference on Harmonisation Good Clinical Practice Guidelines. 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 de-identified 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 US and/or EU 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 de-identified 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. Philip G. Conaghan is supported in part through the United Kingdom National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
Keywords
- Functional status
- Osteoarthritis
- Pain
- Patient-reported outcome measures
- Tanezumab
ASJC Scopus subject areas
- Rheumatology
- Immunology and Allergy