Interferon-γ release assay versus tuberculin skin test prior to treatment with golimumab, a human anti–tumor necrosis factor antibody, in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis

Authors

  • Elizabeth C. Hsia,

    Corresponding author
    1. Janssen Research & Development, LLC, Spring House, Pennsylvania, and University of Pennsylvania, Philadelphia
    Current affiliation:
    1. Pfizer, Collegeville, Pennsylvania
    • Clinical Research Immunology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA 19472
    Search for more papers by this author
    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock or stock options in Johnson & Johnson, of which Janssen is a subsidiary.

  • Neil Schluger,

    1. Columbia University, New York, New York
    Search for more papers by this author
    • Drs. Schluger and Chaisson received consulting fees from Janssen/Johnson & Johnson (less than $10,000 each) at the time the study was being conducted.

  • John J. Cush,

    1. Baylor Research Institute, Dallas, Texas
    Search for more papers by this author
    • Dr. Cush has received consulting fees, speaking fees, and/or honoraria from Genentech, Pfizer, Celgene, Corrona, Amgen, Bristol-Myers Squibb, and Janssen (less than $10,000 each) and from UCB and Abbott (more than $10,000 each).

  • Richard E. Chaisson,

    1. Johns Hopkins University, Baltimore, Maryland
    Search for more papers by this author
    • Drs. Schluger and Chaisson received consulting fees from Janssen/Johnson & Johnson (less than $10,000 each) at the time the study was being conducted.

  • Eric L. Matteson,

    1. Mayo Clinic, Rochester, Minnesota
    Search for more papers by this author
    • Dr. Matteson has received consulting fees, speaking fees, and/or honoraria from Janssen (less than $10,000) and has received research funding and grants from Janssen.

  • Stephen Xu,

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

  • Anna Beutler,

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

  • Mittie K. Doyle,

    1. Janssen Research & Development, LLC, Spring House, Pennsylvania, and University of Pennsylvania, Philadelphia
    Search for more papers by this author
    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock or stock options in Johnson & Johnson, of which Janssen is a subsidiary.

  • Benjamin Hsu,

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

  • Mahboob U. Rahman

    1. Janssen Research & Development, LLC, Spring House, Pennsylvania, and University of Pennsylvania, Philadelphia
    Current affiliation:
    1. Pfizer, Collegeville, Pennsylvania
    Search for more papers by this author
    • Drs. Hsia, Beutler, Doyle, Hsu, and Rahman and Mr. Xu own stock or stock options in Johnson & Johnson, of which Janssen is a subsidiary.


Abstract

Objective

To evaluate the performance of an interferon-γ release assay (IGRA) versus the standard tuberculin skin test (TST) as a screening tool for latent tuberculosis (TB) infection prior to the initiation of anti–tumor necrosis factor therapy in patients with autoimmune inflammatory diseases.

Methods

This integrated analysis involved screening of patients with rheumatoid arthritis, those with psoriatic arthritis, and those with ankylosing spondylitis from phase III trials of golimumab. The IGRA used to screen for latent TB was the QuantiFERON-TB Gold In-Tube test.

Results

In this pooled analysis, 2,282 patients underwent both IGRA and TST screening prior to golimumab treatment. Among these patients, 13.8% had at least one test yielding positive findings for latent TB, including 9.4% with positive results by TST, 7.0% with positive results by IGRA, and 2.6% with positive results on both tests. The rate of indeterminate results for TB on IGRA was 1.8%. Agreement between the TST and IGRA results, measured by the kappa coefficient, was 0.22 (95% confidence interval 0.157–0.279; P = 0.021). Among the patients with positive IGRA findings, 36.9% had positive TST findings. Among the patients with positive TST findings, 27.4% had positive IGRA findings. Overall, 781 (34.2%) of the 2,282 patients had previously received the bacillus Calmette-Guérin (BCG) vaccine; among this vaccinated group, the rate of positivity for latent TB by TST was 15.2% (119 of 781), compared to a rate of positivity of 9.1% (71 of 781) by IGRA (P = 0.0002). Among patients who had not received the BCG vaccine, the rate of positivity by TST was 5.0% (62 of 1,248) and the rate of positivity by IGRA was 5.8% (72 of 1,248) (P = 0.3745). When the IGRA was repeated in patients whose results were initially indeterminate, the rate of indeterminate IGRA findings for latent TB was much lower than has been previously reported.

Conclusion

In the absence of a true gold standard test for latent TB infection, results of this comparison of IGRA and TST in a large cohort of patients with rheumatic diseases suggest that the IGRA provides greater specificity and possibly greater sensitivity than the TST.

Ancillary