Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelve-month data from a twenty-four–month phase III randomized radiographic study†‡
Corresponding Author
Désirée van der Heijde
Leiden University Medical Center, Leiden, The Netherlands
Dr. van der Heijde has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Otsuka, Pfizer Inc., Roche, Sanofi-Aventis, Schering-Plough, UCB, and Wyeth (less than $10,000 each).
Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The NetherlandsSearch for more papers by this authorYoshiya Tanaka
University of Occupational and Environmental Health, Kitakyushu, Japan
Dr. Tanaka has received consulting fees, speaking fees, and/or honoraria from Eisai Pharma, Pfizer Inc., Abbott, Immunol Pharma, Janssen, Takeda, AstraZeneca, Astellas Pharma, Asahi Kasei Pharma, and GlaxoSmithKline (less than $10,000 each) and from Chugai Pharma and Mitsubishi Tanabe Pharma (more than $10,000 each).
Search for more papers by this authorRoy Fleischmann
Metroplex Clinical Research Center, Dallas, Texas
Dr. Fleischmann has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Centocor, Bristol-Myers Squibb, Roche, Pfizer Inc., Eli Lilly, USB, Sanofi-Aventis, and Lexicon (less than $10,000 each) and a study grant from Pfizer Inc.
Search for more papers by this authorEdward Keystone
University of Toronto, Toronto, Ontario, Canada
Dr. Keystone has received consulting fees, speaking fees, and/or honoraria from Abbott, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, Hoffmann-La Roche, Genentech, Merck, Nycomed, Pfizer Inc., and UCB (less than $10,000 each) and research funding from Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Hoffmann-La Roche, Genzyme, Merck, Novartis, Pfizer Inc., and UCB.
Search for more papers by this authorJoel Kremer
Albany Medical College, Albany, New York
Dr. Kremer has received consulting fees, speaking fees, and/or honoraria from Pfizer Inc. (more than $10,000).
Search for more papers by this authorCristiano Zerbini
Centro Paulista de Investigação Clinica, São Paulo, Brazil
Search for more papers by this authorMario H. Cardiel
Centro de Investigacion Clinica de Morelia, Morelia, Mexico
Search for more papers by this authorStanley Cohen
Metroplex Clinical Research Center, Dallas, Texas
Dr. Cohen has received consulting fees, speaking fees, and/or honoraria from Amgen, Biogen-IDEC, Bristol-Myers Squibb, Centocor, Flexxion Therapeutics, Genentech, Johnson & Johnson, Pfizer Inc., Merck, Procter & Gamble, and Roche (less than $10,000 each).
Search for more papers by this authorPeter Nash
Nambour Hospital, Sunshine Coast Nambour, Queensland, Australia, and University of Queensland, St. Lucia, Queensland, Australia
Search for more papers by this authorYeong-Wook Song
Seoul National University Hospital, Seoul, Korea
Search for more papers by this authorBradley T. Wyman
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorDavid Gruben
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorBirgitta Benda
Pfizer Inc, Collegeville, Pennsylvania
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorGene Wallenstein
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorSriram Krishnaswami
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorSamuel H. Zwillich
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorJohn D. Bradley
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorCarol A. Connell
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorand the ORAL Scan Investigators
Search for more papers by this authorCorresponding Author
Désirée van der Heijde
Leiden University Medical Center, Leiden, The Netherlands
Dr. van der Heijde has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Chugai, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Otsuka, Pfizer Inc., Roche, Sanofi-Aventis, Schering-Plough, UCB, and Wyeth (less than $10,000 each).
Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The NetherlandsSearch for more papers by this authorYoshiya Tanaka
University of Occupational and Environmental Health, Kitakyushu, Japan
Dr. Tanaka has received consulting fees, speaking fees, and/or honoraria from Eisai Pharma, Pfizer Inc., Abbott, Immunol Pharma, Janssen, Takeda, AstraZeneca, Astellas Pharma, Asahi Kasei Pharma, and GlaxoSmithKline (less than $10,000 each) and from Chugai Pharma and Mitsubishi Tanabe Pharma (more than $10,000 each).
Search for more papers by this authorRoy Fleischmann
Metroplex Clinical Research Center, Dallas, Texas
Dr. Fleischmann has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Centocor, Bristol-Myers Squibb, Roche, Pfizer Inc., Eli Lilly, USB, Sanofi-Aventis, and Lexicon (less than $10,000 each) and a study grant from Pfizer Inc.
Search for more papers by this authorEdward Keystone
University of Toronto, Toronto, Ontario, Canada
Dr. Keystone has received consulting fees, speaking fees, and/or honoraria from Abbott, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, Hoffmann-La Roche, Genentech, Merck, Nycomed, Pfizer Inc., and UCB (less than $10,000 each) and research funding from Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, Hoffmann-La Roche, Genzyme, Merck, Novartis, Pfizer Inc., and UCB.
Search for more papers by this authorJoel Kremer
Albany Medical College, Albany, New York
Dr. Kremer has received consulting fees, speaking fees, and/or honoraria from Pfizer Inc. (more than $10,000).
Search for more papers by this authorCristiano Zerbini
Centro Paulista de Investigação Clinica, São Paulo, Brazil
Search for more papers by this authorMario H. Cardiel
Centro de Investigacion Clinica de Morelia, Morelia, Mexico
Search for more papers by this authorStanley Cohen
Metroplex Clinical Research Center, Dallas, Texas
Dr. Cohen has received consulting fees, speaking fees, and/or honoraria from Amgen, Biogen-IDEC, Bristol-Myers Squibb, Centocor, Flexxion Therapeutics, Genentech, Johnson & Johnson, Pfizer Inc., Merck, Procter & Gamble, and Roche (less than $10,000 each).
Search for more papers by this authorPeter Nash
Nambour Hospital, Sunshine Coast Nambour, Queensland, Australia, and University of Queensland, St. Lucia, Queensland, Australia
Search for more papers by this authorYeong-Wook Song
Seoul National University Hospital, Seoul, Korea
Search for more papers by this authorBradley T. Wyman
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorDavid Gruben
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorBirgitta Benda
Pfizer Inc, Collegeville, Pennsylvania
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorGene Wallenstein
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorSriram Krishnaswami
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorSamuel H. Zwillich
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorJohn D. Bradley
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorCarol A. Connell
Pfizer Inc, Groton, Connecticut
Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.
Search for more papers by this authorand the ORAL Scan Investigators
Search for more papers by this authorClinicalTrials.gov identifier: NCT00847613.
Presented in part at the 75th Annual Scientific Meeting of the American College of Rheumatology, Chicago, IL, November 2011.
Abstract
Objective
The purpose of this 24-month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Data from a planned 12-month interim analysis are reported.
Methods
In this double-blind, parallel-group, placebo-controlled study, patients receiving background MTX were randomized 4:4:1:1 to tofacitinib at 5 mg twice daily, tofacitinib at 10 mg twice daily, placebo to tofacitinib at 5 mg twice daily, and placebo to tofacitinib at 10 mg twice daily. At month 3, nonresponder placebo-treated patients were advanced in a blinded manner to receive tofacitinib as indicated above; remaining placebo-treated patients were advanced at 6 months. Four primary efficacy end points were all analyzed in a step-down procedure.
Results
At month 6, response rates according to the American College of Rheumatology 20% improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo (51.5% and 61.8%, respectively, versus 25.3%; both P < 0.0001). At month 6, least squares mean (LSM) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06, respectively, versus 0.47 for placebo (P = 0.0792 and P ≤ 0.05, respectively). At month 3, LSM changes in the Health Assessment Questionnaire disability index score for tofacitinib at 5 mg and 10 mg twice daily were –0.40 (significance not declared due to step-down procedure) and –0.54 (P < 0.0001), respectively, versus –0.15 for placebo. At month 6, rates of remission (defined as a value <2.6 for the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate) for tofacitinib at 5 mg and 10 mg twice daily were 7.2% (significance not declared due to step-down procedure) and 16.0% (P < 0.0001), respectively, versus 1.6% for placebo. The safety profile was consistent with findings in previous studies.
Conclusion
Data from this 12-month interim analysis demonstrate that tofacitinib inhibits progression of structural damage and improves disease activity in patients with RA who are receiving MTX.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
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| ART_37816_sm_SupplData.doc445 KB | Supplementary Data |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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Kremer JM,
Zerbini C,
Lee EB,
Gruben D,
Krishnaswami S,
Zwillich SH, et al.
Tofacitinib (CP-690,550), an oral Janus kinase inhibitor: analysis of efficacy endpoints by subgroups in a pooled phase 2 and 3 rheumatoid arthritis study population [abstract].
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10.1136/annrheumdis-2012-eular.2108 Google Scholar
