Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis

Authors

  • Daniel J. Lovell,

    Corresponding author
    1. Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    • Children's Hospital Medical Center, Location E, Room 2-129, 3333 Burnet Avenue, Cincinnati, OH 45229
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    • Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Centocor, Wyeth, Bristol-Myers Squibb, Amgen, Abbott, Pfizer, Regeneron, Novartis, and Hoffmann-La Roche. Dr. Reiff has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Amgen, Abbott, Wyeth, Merck, Pfizer, and Novartis and has served as an expert witness on behalf of Pfizer concerning FDA rehearsal. Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, Bristol-Myers Squibb, and Abbott. Dr. Wallace has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Pfizer, Novartis, and Bristol-Myers Squibb and has received research grants (more than $10,000 each) from Pfizer and Centocor. Drs. Chon, Lin, and Baumgartner hold stock and/or stock options in Amgen. Dr. Giannini has been awarded a research grant (to Children's Hospital Medical Center) from Amgen for clinical trial expenses.

  • Andreas Reiff,

    1. University of Southern California, Los Angeles, California
    2. Childrens Hospital Los Angeles, Los Angeles, California
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    • Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Centocor, Wyeth, Bristol-Myers Squibb, Amgen, Abbott, Pfizer, Regeneron, Novartis, and Hoffmann-La Roche. Dr. Reiff has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Amgen, Abbott, Wyeth, Merck, Pfizer, and Novartis and has served as an expert witness on behalf of Pfizer concerning FDA rehearsal. Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, Bristol-Myers Squibb, and Abbott. Dr. Wallace has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Pfizer, Novartis, and Bristol-Myers Squibb and has received research grants (more than $10,000 each) from Pfizer and Centocor. Drs. Chon, Lin, and Baumgartner hold stock and/or stock options in Amgen. Dr. Giannini has been awarded a research grant (to Children's Hospital Medical Center) from Amgen for clinical trial expenses.

  • Norman T. Ilowite,

    1. Albert Einstein College of Medicine, Bronx, New York
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    • Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Centocor, Wyeth, Bristol-Myers Squibb, Amgen, Abbott, Pfizer, Regeneron, Novartis, and Hoffmann-La Roche. Dr. Reiff has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Amgen, Abbott, Wyeth, Merck, Pfizer, and Novartis and has served as an expert witness on behalf of Pfizer concerning FDA rehearsal. Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, Bristol-Myers Squibb, and Abbott. Dr. Wallace has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Pfizer, Novartis, and Bristol-Myers Squibb and has received research grants (more than $10,000 each) from Pfizer and Centocor. Drs. Chon, Lin, and Baumgartner hold stock and/or stock options in Amgen. Dr. Giannini has been awarded a research grant (to Children's Hospital Medical Center) from Amgen for clinical trial expenses.

  • Carol A. Wallace,

    1. Children's Hospital and Regional Medical Center, Seattle, Washington
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    • Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Centocor, Wyeth, Bristol-Myers Squibb, Amgen, Abbott, Pfizer, Regeneron, Novartis, and Hoffmann-La Roche. Dr. Reiff has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Amgen, Abbott, Wyeth, Merck, Pfizer, and Novartis and has served as an expert witness on behalf of Pfizer concerning FDA rehearsal. Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, Bristol-Myers Squibb, and Abbott. Dr. Wallace has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Pfizer, Novartis, and Bristol-Myers Squibb and has received research grants (more than $10,000 each) from Pfizer and Centocor. Drs. Chon, Lin, and Baumgartner hold stock and/or stock options in Amgen. Dr. Giannini has been awarded a research grant (to Children's Hospital Medical Center) from Amgen for clinical trial expenses.

  • Yun Chon,

    1. Amgen Inc., Thousand Oaks, California
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    • Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Centocor, Wyeth, Bristol-Myers Squibb, Amgen, Abbott, Pfizer, Regeneron, Novartis, and Hoffmann-La Roche. Dr. Reiff has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Amgen, Abbott, Wyeth, Merck, Pfizer, and Novartis and has served as an expert witness on behalf of Pfizer concerning FDA rehearsal. Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, Bristol-Myers Squibb, and Abbott. Dr. Wallace has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Pfizer, Novartis, and Bristol-Myers Squibb and has received research grants (more than $10,000 each) from Pfizer and Centocor. Drs. Chon, Lin, and Baumgartner hold stock and/or stock options in Amgen. Dr. Giannini has been awarded a research grant (to Children's Hospital Medical Center) from Amgen for clinical trial expenses.

  • Shao-Lee Lin,

    1. Amgen Inc., Thousand Oaks, California
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    • Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Centocor, Wyeth, Bristol-Myers Squibb, Amgen, Abbott, Pfizer, Regeneron, Novartis, and Hoffmann-La Roche. Dr. Reiff has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Amgen, Abbott, Wyeth, Merck, Pfizer, and Novartis and has served as an expert witness on behalf of Pfizer concerning FDA rehearsal. Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, Bristol-Myers Squibb, and Abbott. Dr. Wallace has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Pfizer, Novartis, and Bristol-Myers Squibb and has received research grants (more than $10,000 each) from Pfizer and Centocor. Drs. Chon, Lin, and Baumgartner hold stock and/or stock options in Amgen. Dr. Giannini has been awarded a research grant (to Children's Hospital Medical Center) from Amgen for clinical trial expenses.

  • Scott W. Baumgartner,

    1. Amgen Inc., Thousand Oaks, California
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    • Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Centocor, Wyeth, Bristol-Myers Squibb, Amgen, Abbott, Pfizer, Regeneron, Novartis, and Hoffmann-La Roche. Dr. Reiff has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Amgen, Abbott, Wyeth, Merck, Pfizer, and Novartis and has served as an expert witness on behalf of Pfizer concerning FDA rehearsal. Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, Bristol-Myers Squibb, and Abbott. Dr. Wallace has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Pfizer, Novartis, and Bristol-Myers Squibb and has received research grants (more than $10,000 each) from Pfizer and Centocor. Drs. Chon, Lin, and Baumgartner hold stock and/or stock options in Amgen. Dr. Giannini has been awarded a research grant (to Children's Hospital Medical Center) from Amgen for clinical trial expenses.

  • Edward H. Giannini

    1. Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
    Search for more papers by this author
    • Dr. Lovell has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Centocor, Wyeth, Bristol-Myers Squibb, Amgen, Abbott, Pfizer, Regeneron, Novartis, and Hoffmann-La Roche. Dr. Reiff has received consulting fees, speaking fees, and/or honoraria (less than $10,000) from Amgen, Abbott, Wyeth, Merck, Pfizer, and Novartis and has served as an expert witness on behalf of Pfizer concerning FDA rehearsal. Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Novartis, Bristol-Myers Squibb, and Abbott. Dr. Wallace has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Amgen, Pfizer, Novartis, and Bristol-Myers Squibb and has received research grants (more than $10,000 each) from Pfizer and Centocor. Drs. Chon, Lin, and Baumgartner hold stock and/or stock options in Amgen. Dr. Giannini has been awarded a research grant (to Children's Hospital Medical Center) from Amgen for clinical trial expenses.


  • ClinicalTrials.gov identifier: NCT00357903.

Abstract

Objective

To evaluate the safety and efficacy of up to 8 years of etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA).

Methods

Patients with JRA who previously participated in a randomized controlled trial (RCT) of etanercept were eligible to receive etanercept in a long-term open-label extension (OLE) trial. Safety end points included the incidences of serious adverse events (SAEs), medically important infections (MIIs), and death. Efficacy end points included the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement.

Results

Of the 69 patients originally enrolled in the RCT, 58 (84%) participated in the OLE, for a total of 318 patient-years of etanercept exposure. A total of 42 of the 58 patients (72%) entered the fourth year of continuous etanercept treatment, and 26 patients (45%) entered the eighth year. Sixteen patients (23% of those entering the RCT) reported 39 SAEs. The overall rate of SAEs (0.12 per patient-year) did not increase with long-term exposure to etanercept. The rate of MIIs (0.03 per patient-year) remained low; 1 new MII was reported in patients with ≥5 years of etanercept exposure. No cases of tuberculosis, opportunistic infections, malignancies, lymphomas, lupus, demyelinating disorders, or deaths were reported. An ACR Pedi 70 response or higher was achieved by 100% of patients with 8 years of data (11 of 11) and by 61% of patients according to the last observation carried forward data (28 of 46).

Conclusion

These data suggest that the acceptable safety profile of etanercept therapy is maintained for up to 8 years in this population of JRA patients. Improvements in the signs and symptoms of JRA were also maintained for up to 8 years.

Ancillary