Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelve-month data from a twenty-four–month phase III randomized radiographic study

Authors

  • Désirée van der Heijde,

    Corresponding author
    1. Leiden University Medical Center, Leiden, The Netherlands
    • Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    Search for more papers by this author
    • 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).

  • Yoshiya Tanaka,

    1. University of Occupational and Environmental Health, Kitakyushu, Japan
    Search for more papers by this author
    • 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).

  • Roy Fleischmann,

    1. Metroplex Clinical Research Center, Dallas, Texas
    Search for more papers by this author
    • 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.

  • Edward Keystone,

    1. University of Toronto, Toronto, Ontario, Canada
    Search for more papers by this author
    • 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.

  • Joel Kremer,

    1. Albany Medical College, Albany, New York
    Search for more papers by this author
    • Dr. Kremer has received consulting fees, speaking fees, and/or honoraria from Pfizer Inc. (more than $10,000).

  • Cristiano Zerbini,

    1. Centro Paulista de Investigação Clinica, São Paulo, Brazil
    Search for more papers by this author
  • Mario H. Cardiel,

    1. Centro de Investigacion Clinica de Morelia, Morelia, Mexico
    Search for more papers by this author
  • Stanley Cohen,

    1. Metroplex Clinical Research Center, Dallas, Texas
    Search for more papers by this author
    • 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).

  • Peter Nash,

    1. Nambour Hospital, Sunshine Coast Nambour, Queensland, Australia, and University of Queensland, St. Lucia, Queensland, Australia
    Search for more papers by this author
  • Yeong-Wook Song,

    1. Seoul National University Hospital, Seoul, Korea
    Search for more papers by this author
  • Dana Tegzová,

    1. Institute of Rheumatology, Prague, Czech Republic
    Search for more papers by this author
  • Bradley T. Wyman,

    1. Pfizer Inc, Groton, Connecticut
    Search for more papers by this author
    • Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.

  • David Gruben,

    1. Pfizer Inc, Groton, Connecticut
    Search for more papers by this author
    • Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.

  • Birgitta Benda,

    1. Pfizer Inc, Collegeville, Pennsylvania
    Search for more papers by this author
    • Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.

  • Gene Wallenstein,

    1. Pfizer Inc, Groton, Connecticut
    Search for more papers by this author
    • Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.

  • Sriram Krishnaswami,

    1. Pfizer Inc, Groton, Connecticut
    Search for more papers by this author
    • Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.

  • Samuel H. Zwillich,

    1. Pfizer Inc, Groton, Connecticut
    Search for more papers by this author
    • Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.

  • John D. Bradley,

    1. Pfizer Inc, Groton, Connecticut
    Search for more papers by this author
    • Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.

  • Carol A. Connell,

    1. Pfizer Inc, Groton, Connecticut
    Search for more papers by this author
    • Drs. Wyman, Gruben, Benda, Wallenstein, Krishnaswami, Zwillich, Bradley, and Connell own stock or stock options in Pfizer Inc.

  • and the ORAL Scan Investigators


  • ClinicalTrials.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.

Ancillary