Immunogenicity, Safety, and Efficacy of Abatacept Administered Subcutaneously With or Without Background Methotrexate in Patients With Rheumatoid Arthritis: Results From a Phase III, International, Multicenter, Parallel-Arm, Open-Label Study

Authors

  • Peter Nash,

    Corresponding author
    1. University of Queensland, Brisbane, Queensland, Australia
    • Department of Medicine, University of Queensland, 288 Herston Road, Brisbane, Queensland 4006, Australia

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    • Dr. Nash has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Bristol-Myers Squibb.

  • Sauithree Nayiager,

    1. St. Augustine's Hospital, Durban, South Africa
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  • Mark C. Genovese,

    1. Stanford University, Palo Alto, California
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    • Dr. Genovese has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Bristol-Myers Squibb.

  • Alan J. Kivitz,

    1. Altoona Center for Clinical Research, Duncansville, Pennsylvania
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    • Dr. Kivitz has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from and owns stock or stock options in Bristol-Myers Squibb.

  • Kurt Oelke,

    1. Rheumatic Disease Center, Milwaukee, Wisconsin
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    • Dr. Oelke has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Pfizer, Amgen, Sanofi-Aventis, URL Pharma, Abbott, and UCB.

  • Charles Ludivico,

    1. East Penn Rheumatology Associates, Bethlehem, Pennsylvania
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    • Dr. Ludivico has received consultant fees and/or speaking fees (less than $10,000 each) from Bristol-Myers Squibb, Roche, and UCB.

  • William Palmer,

    1. Westroads Medical Group, Omaha, Nebraska
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    • Dr. Palmer has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Bristol-Myers Squibb and Amgen/Pfizer.

  • Cristian Rodriguez,

    1. Bristol-Myers Squibb, Princeton, New Jersey
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    • Drs. Rodriguez, Delaet, and Elegbe own stock or stock options in Bristol-Myers Squibb.

  • Ingrid Delaet,

    1. Bristol-Myers Squibb, Princeton, New Jersey
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    • Drs. Rodriguez, Delaet, and Elegbe own stock or stock options in Bristol-Myers Squibb.

  • Ayanbola Elegbe,

    1. Bristol-Myers Squibb, Princeton, New Jersey
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    • Drs. Rodriguez, Delaet, and Elegbe own stock or stock options in Bristol-Myers Squibb.

  • Michael Corbo

    1. Bristol-Myers Squibb, Princeton, New Jersey
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    • Dr. Corbo owns stock or stock options in Bristol-Myers Squibb and has received fees from Bristol-Myers Squibb for patents pending approval.


  • ClinicalTrials.gov identifier: NCT00547521.

Abstract

Objective

To evaluate the impact of concomitant methotrexate (MTX) on subcutaneous (SC) abatacept immunogenicity, and to assess safety and efficacy.

Methods

This phase III, open-label study had a 4-month short-term (ST) period and an ongoing long-term extension (LTE) period. Rheumatoid arthritis patients were stratified to receive SC abatacept (125 mg/week) with (combination) or without MTX (monotherapy), with no intravenous loading dose; patients receiving monotherapy could add MTX in the LTE period. Immunogenicity (percentage of anti-abatacept antibody–positive patients) was assessed. ST and LTE period data are reported, including efficacy through LTE month 14 and safety through LTE month 20.

Results

Ninety-six of 100 enrolled patients completed the ST period; 3.9% (combination) and 4.1% of patients (monotherapy) developed transient immunogenicity, and no patients were antibody positive at month 4. Serious adverse events (SAEs) were reported in 3.9% (combination) and 6.1% of patients (monotherapy); 5.9% (combination) and 8.2% of patients (monotherapy) experienced SC injection reactions, and all were mild in intensity. Mean 28-joint Disease Activity Score (DAS28) changes were −1.67 (95% confidence interval [95% CI] −2.06, −1.28; combination) and −1.94 (95% CI −2.46, −1.42; monotherapy) at month 4. Ninety patients entered and were treated in the LTE period; 83.3% (75 of 90) remained ongoing at month 24. One LTE-treated patient (1.1%) developed immunogenicity, 14.4% of patients experienced SAEs, and no SC injection reactions were reported. For patients entering the LTE period, mean DAS28 changes from baseline were −1.84 (95% CI −2.23, −1.34; combination) and −2.86 (95% CI −3.46, −2.27; monotherapy) at month 18.

Conclusion

SC abatacept did not elicit immunogenicity associated with loss of safety or efficacy, either with or without MTX.

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