Golimumab, a human anti–tumor necrosis factor α monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: Twenty-four–week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis

Authors

  • Paul Emery,

    Corresponding author
    1. University of Leeds, Leeds, UK
    • Academic Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK
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    • Dr. Emery has received consulting fees and/or honoraria from Centocor (less than $10,000) and has served as a study investigator for Centocor.

  • Roy M. Fleischmann,

    1. University of Texas Southwestern Medical Center at Dallas
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    • Dr. Fleischmann has received consulting fees from Abbott, Wyeth, Amgen, Centocor, Genentech, Pfizer, Astra-Zeneca, UCB, and Roche (less than $10,000 each), has received speaking fees from Abbott, Wyeth, Amgen, Genentech, and Roche (less than $10,000 each), and has served as a study investigator for Abbott, Wyeth, Amgen, Centocor, Genentech, Pfizer, UCB, and Roche.

  • Larry W. Moreland,

    1. University of Pittsburgh, Pittsburgh, Pennsylvania
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    • Dr. Moreland has received consulting fees, speaking fees, and/or honoraria from Centocor and Johnson & Johnson (less than $10,000 each) and has served as a study investigator for Centocor.

  • Elizabeth C. Hsia,

    1. Centocor Research and Development, Malvern, Pennsylvania, and University of Pennsylvania School of Medicine, Philadelphia
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    • Dr. Hsia owns stock or stock options in Centocor/Johnson & Johnson.

  • Ingrid Strusberg,

    1. Centro Reumatológico Strusberg, Cordoba, Argentina
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    • Dr. Strusberg has received consulting fees, speaking fees, and/or honoraria from Schering-Plough and Bristol-Myers Squibb (less than $10,000 each).

  • Patrick Durez,

    1. Université Catholique de Louvain, Brussels, Belgium
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    • Dr. Durez has received consulting fees, speaking fees, and/or honoraria from Centocor, Bristol-Myers Squibb, Abbott, and Roche (less than $10,000 each).

  • Peter Nash,

    1. University of Queensland, Brisbane, Queensland, Australia
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    • Dr. Nash has received consulting fees and speaking fees from Schering-Plough (less than $10,000 each) and has served as a study investigator for Centocor.

  • Eric Jason B. Amante,

    1. University of the Philippines–Philippine General Hospital, Manila, Philippines
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    • Dr. Amante has received speaking fees from Pfizer, Roche, Schering-Plough, Johnson & Johnson, and Merck, Sharp, and Dohme (less than $10,000 each).

  • Melvin Churchill,

    1. Arthritis Center of Nebraska, Lincoln
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  • Won Park,

    1. Inha University Hospital, Incheon, South Korea
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  • Bernardo Antonio Pons-Estel,

    1. Sanatorio Parque, Santa Fe, Argentina
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  • Mittie K. Doyle,

    1. Centocor Research and Development, Malvern, Pennsylvania, and University of Pennsylvania School of Medicine, Philadelphia
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    • Dr. Doyle owns stock or stock options in Centocor/Johnson & Johnson.

  • Sudha Visvanathan,

    1. Centocor Research and Development, Malvern, Pennsylvania
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    • Dr. Visvanathan owns stock or stock options in Johnson & Johnson.

  • Weichun Xu,

    1. Centocor Research and Development, Malvern, Pennsylvania
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  • Mahboob U. Rahman

    1. Centocor Research and Development, Malvern, Pennsylvania, and University of Pennsylvania School of Medicine, Philadelphia
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    • Dr. Rahman owns stock or stock options in Johnson & Johnson.

Errata

This article is corrected by:

  1. Errata: Erratum: Golimumab, a human anti-tumor necrosis factor α monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: Twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis Volume 62, Issue 9, 2812, Article first published online: 16 September 2010

  • EudraCT Database no. 2004-003295-10.

Abstract

Objective

To assess the safety and efficacy of golimumab in methotrexate (MTX)–naive patients with active rheumatoid arthritis (RA).

Methods

MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1).

Results

An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P = 0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P = 0.049) and between group 3 (40.5%; P = 0.038) but not group 4 (36.5%; P = 0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound −5.2%; predefined delta value for noninferiority −10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively.

Conclusion

Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns.

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