Efficacy and safety of adalimumab in patients with ankylosing spondylitis: Results of a multicenter, randomized, double-blind, placebo-controlled trial

Authors

  • Désirée van der Heijde,

    1. University Hospital Maastricht, Maastricht, The Netherlands
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    • Dr. van der Heijde has received research support from, or is a consultant for, Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Schering-Plough, and Wyeth. Dr. Schiff has received grant/research support from, is on the Speaker's Bureau of, or is a consultant for, Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Merck, Novartis, Roche, and Wyeth-Ayerst. Drs. Dijkmans and Dougados have received consulting fees from Abbott. Drs. Wong and Kupper hold stock options as a benefit of their employment with Abbott. Dr. Davis has received research support from, or is a consultant for, Abbott, Amgen, and Centocor.

  • Alan Kivitz,

    1. Altoona Center for Clinical Research, Duncansville, Pennsylvania
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  • Michael H. Schiff,

    1. Denver Arthritis Clinic Research Unit, Denver, Colorado
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    • Dr. van der Heijde has received research support from, or is a consultant for, Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Schering-Plough, and Wyeth. Dr. Schiff has received grant/research support from, is on the Speaker's Bureau of, or is a consultant for, Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Merck, Novartis, Roche, and Wyeth-Ayerst. Drs. Dijkmans and Dougados have received consulting fees from Abbott. Drs. Wong and Kupper hold stock options as a benefit of their employment with Abbott. Dr. Davis has received research support from, or is a consultant for, Abbott, Amgen, and Centocor.

  • Joachim Sieper,

    1. Benjamin Franklin Hospital, Free University Berlin, and German Rheumatism Research Center, Berlin, Germany
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  • Ben A. C. Dijkmans,

    1. Department of Rheumatology, VU Medical Center, and Jan van Breemen Institute, Amsterdam, The Netherlands
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    • Dr. van der Heijde has received research support from, or is a consultant for, Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Schering-Plough, and Wyeth. Dr. Schiff has received grant/research support from, is on the Speaker's Bureau of, or is a consultant for, Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Merck, Novartis, Roche, and Wyeth-Ayerst. Drs. Dijkmans and Dougados have received consulting fees from Abbott. Drs. Wong and Kupper hold stock options as a benefit of their employment with Abbott. Dr. Davis has received research support from, or is a consultant for, Abbott, Amgen, and Centocor.

  • Jürgen Braun,

    1. University Medical Center Ruhrgebiet, Herne, Germany
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  • Maxime Dougados,

    1. Hôpital Cochin, University of Paris, Paris, France
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    • Dr. van der Heijde has received research support from, or is a consultant for, Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Schering-Plough, and Wyeth. Dr. Schiff has received grant/research support from, is on the Speaker's Bureau of, or is a consultant for, Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Merck, Novartis, Roche, and Wyeth-Ayerst. Drs. Dijkmans and Dougados have received consulting fees from Abbott. Drs. Wong and Kupper hold stock options as a benefit of their employment with Abbott. Dr. Davis has received research support from, or is a consultant for, Abbott, Amgen, and Centocor.

  • John D. Reveille,

    1. University of Texas at Houston
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  • Robert L. Wong,

    1. Abbott Laboratories, Parsippany, New Jersey
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    • Dr. van der Heijde has received research support from, or is a consultant for, Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Schering-Plough, and Wyeth. Dr. Schiff has received grant/research support from, is on the Speaker's Bureau of, or is a consultant for, Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Merck, Novartis, Roche, and Wyeth-Ayerst. Drs. Dijkmans and Dougados have received consulting fees from Abbott. Drs. Wong and Kupper hold stock options as a benefit of their employment with Abbott. Dr. Davis has received research support from, or is a consultant for, Abbott, Amgen, and Centocor.

  • Hartmut Kupper,

    1. Abbott GmbH & Co. KG, Ludwigshafen, Germany
    Search for more papers by this author
    • Dr. van der Heijde has received research support from, or is a consultant for, Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Schering-Plough, and Wyeth. Dr. Schiff has received grant/research support from, is on the Speaker's Bureau of, or is a consultant for, Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Merck, Novartis, Roche, and Wyeth-Ayerst. Drs. Dijkmans and Dougados have received consulting fees from Abbott. Drs. Wong and Kupper hold stock options as a benefit of their employment with Abbott. Dr. Davis has received research support from, or is a consultant for, Abbott, Amgen, and Centocor.

  • John C. Davis Jr.

    Corresponding author
    1. University of California, San Francisco
    • University of California, San Francisco, 533 Parnassus Avenue, Room U386, Box 0633, San Francisco, CA 94143
    Search for more papers by this author
    • Dr. van der Heijde has received research support from, or is a consultant for, Abbott, Amgen, Bristol-Myers Squibb, Centocor, Merck, Schering-Plough, and Wyeth. Dr. Schiff has received grant/research support from, is on the Speaker's Bureau of, or is a consultant for, Abbott, Amgen, Aventis, Bristol-Myers Squibb, Centocor, Merck, Novartis, Roche, and Wyeth-Ayerst. Drs. Dijkmans and Dougados have received consulting fees from Abbott. Drs. Wong and Kupper hold stock options as a benefit of their employment with Abbott. Dr. Davis has received research support from, or is a consultant for, Abbott, Amgen, and Centocor.


Abstract

Objective

To evaluate the safety and efficacy of adalimumab, a fully human recombinant IgG1 monoclonal antibody that specifically targets human tumor necrosis factor, in patients with active ankylosing spondylitis (AS).

Methods

This was a multicenter, randomized (2:1 ratio), double-blind, placebo-controlled study to evaluate a subcutaneous injection of adalimumab, 40 mg every other week, compared with placebo for 24 weeks. The primary efficacy end point was the percentage of patients with a 20% response according to the ASsessment in Ankylosing Spondylitis International Working Group criteria for improvement (ASAS20) at week 12. Secondary outcome measures included the ASAS20 at week 24 and multiple measures of disease activity, spinal mobility, and function, as well as ASAS partial remission.

Results

At week 12, 58.2% of adalimumab-treated patients (121 of 208) achieved an ASAS20 response, compared with 20.6% of placebo-treated patients (22 of 107) (P < 0.001). More patients in the adalimumab group (45.2% [94 of 208]) than in the placebo group (15.9% [17 of 107]) had at least a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index at week 12 (P < 0.001). Significant improvements in the ASAS40 response and the response according to the ASAS5/6 criteria at weeks 12 and 24 were also demonstrated (P < 0.001). Partial remission was achieved by more adalimumab-treated patients than placebo-treated patients (22.1% versus 5.6%; P < 0.001). Adalimumab-treated patients reported more adverse events (75.0% versus 59.8% of placebo-treated patients; P < 0.05), but there was no statistically significant difference in the incidence of infections. Most adverse events were mild or moderate in severity.

Conclusion

Adalimumab was well-tolerated during the 24-week study period and was associated with a significant and sustained reduction in the signs and symptoms of active AS.

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