Comprehensive tuberculosis screening program in patients with inflammatory arthritides treated with golimumab, a human anti–tumor necrosis factor antibody, in Phase III clinical trials

Authors

  • Elizabeth C. Hsia,

    Corresponding author
    1. Janssen Research & Development, LLC, Spring House, and University of Pennsylvania School of Medicine, Philadelphia
    • Clinical Research Immunology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA 19477
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    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock and/or stock options in Johnson & Johnson, of which Janssen Research & Development, LLC, is a subsidiary.

  • John J. Cush,

    1. Baylor Research Institute and Baylor University Medical Center, Dallas, Texas
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    • Dr. Cush has received consultant fees (less than $10,000 each) from Centocor/Janssen, Savient, Pfizer, BMS, Amgen, and Genentech and (more than $10,000 each) from Abbott and UCB; has received research grants from Genentech, Pfizer, UCB, Celgene, Amgen, the Consortium of Rheumatology Researchers of North America, the NIH, and Novartis; and has served on the Data Safety Monitoring Board for Janssen Research & Development, LLC.

  • Eric L. Matteson,

    1. Mayo Clinic College of Medicine, Rochester, Minnesota
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    • Dr. Matteson has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Johnson & Johnson/Janssen and Novartis; has received grant support from Genentech and Novartis; and has served as an investigator for Biogen Idec, Centocor, Genentech, Hoffmann-La Roche, Human Genome Sciences, Janssen Biotech, Pfizer, Novartis, and UCB Group.

  • Anna Beutler,

    1. Janssen Research & Development, LLC, Spring House, Pennsylvania
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    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock and/or stock options in Johnson & Johnson, of which Janssen Research & Development, LLC, is a subsidiary.

  • Mittie K. Doyle,

    1. Janssen Research & Development, LLC, Spring House, Pennsylvania
    Current affiliation:
    1. Alexion Pharmaceuticals, Cambridge, Massachusetts
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    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock and/or stock options in Johnson & Johnson, of which Janssen Research & Development, LLC, is a subsidiary.

  • Benjamin Hsu,

    1. Janssen Research & Development, LLC, Spring House, Pennsylvania
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    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock and/or stock options in Johnson & Johnson, of which Janssen Research & Development, LLC, is a subsidiary.

  • Stephen Xu,

    1. Janssen Research & Development, LLC, Spring House, Pennsylvania
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    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock and/or stock options in Johnson & Johnson, of which Janssen Research & Development, LLC, is a subsidiary.

  • Mahboob U. Rahman

    1. Janssen Research & Development, LLC, Spring House, Pennsylvania
    Current affiliation:
    1. Pfizer, Collegeville, Pennsylvania
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    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock and/or stock options in Johnson & Johnson, of which Janssen Research & Development, LLC, is a subsidiary.


Abstract

Objective

Reactivation of Mycobacterium tuberculosis infection is a major complication in patients treated with anti–tumor necrosis factor (anti-TNF) agents. We report on the 5 cases of active tuberculosis (TB) that developed in the Golimumab Phase III Program (3 with rheumatoid arthritis, 1 with psoriatic arthritis, and 1 with ankylosing spondylitis) through 1 year among 2,210 patients receiving golimumab.

Methods

Data from global studies were used for an in-depth evaluation of the 5 cases of TB through week 52. Integrated safety data were evaluated for potential hepatotoxicity in patients treated with anti-TB therapy.

Results

No active TB developed among 317 patients receiving golimumab and treated for latent TB with isoniazid. Active TB occurred in 5 patients not treated with isoniazid by week 52 (in 2 patients by week 24); all of the patients had negative TB screening tests (per the local guidelines) and resided in countries with high background rates of TB. No deaths were due to TB. Across all of the groups (placebo and golimumab), alanine aminotransferase and aspartate aminotransferase elevations occurred in greater proportions of patients treated for latent TB infection versus not treated; elevations were largely mild (<3 times the upper limit of normal).

Conclusion

Comprehensive TB screening kept the number of active TB cases relatively low despite conducting the studies in TB-endemic regions. Treatment for latent TB infection appeared effective, since no patients treated for latent TB had TB reactivation. Concurrent treatment with golimumab and anti-TB medication was generally well tolerated. Clinicians should remain vigilant for development of active TB after initiation of TNF inhibitors, since prompt diagnosis and treatment can improve outcomes.

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