Interferon-γ release assay for tuberculosis in patients with psoriasis treated with tumour necrosis factor antagonists: in vivo and in vitro analysis

Br J Dermatol. 2013 Nov;169(5):1133-40. doi: 10.1111/bjd.12544.

Abstract

Background: Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to starting on tumour necrosis factor (TNF) blockers.

Objectives: To investigate the longitudinal changes of interferon (IFN)-γ response to Mycobacterium tuberculosis-specific antigens by serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing in patients with psoriasis during long-term anti-TNF therapy. The direct in vitro effect of adalimumab on IFN-γ secretion was also evaluated.

Methods: In total, 148 patients with psoriasis designated to start anti-TNF treatment were enrolled. We performed a tuberculin skin test at screening, and QFT-GIT at baseline and serially for 24 months after TNF antagonist onset.

Results: At screening, QFT-GIT was positive in 22.3% of the patients, negative in 73.6% and indeterminate in 4%. The IFN-γ response following isoniazid therapy declined and became QFT-GIT negative in 8% of 26 patients with LTBI; in 69% of subjects with LTBI the QFT-GIT remained persistently positive with a significant increase of IFN-γ levels during the follow-up, even if no cases of active tuberculosis were found. Variations of IFN-γ levels were observed also in 7% of 27 patients without LTBI who switched to positive QFT-GIT after 12 or 18 months of biologic therapy, suggesting a new occurrence or reactivation of LTBI. In vitro data showed that in the presence of adalimumab the IFN-γ levels were significantly reduced in a dose-dependent manner (P < 0.05).

Conclusions: Fluctuations of IFN-γ release may occur in patients with psoriasis treated with TNF antagonists. The clinical use of repeated blood tests and the correct interpretation of individual IFN-γ changes could be useful in identifying possible cases of LTBI reactivation or newly acquired tuberculosis infection during long-term anti-TNF treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, Bacterial / metabolism
  • Dermatologic Agents / therapeutic use*
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Interferon-gamma / metabolism
  • Interferon-gamma Release Tests
  • Latent Tuberculosis / complications
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • Opportunistic Infections / complications
  • Psoriasis / complications
  • Psoriasis / drug therapy*
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Risk Factors
  • Tuberculin Test
  • Tuberculosis / complications*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, Bacterial
  • Dermatologic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Infliximab
  • Adalimumab
  • Etanercept