title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania 19472, USA. ehsia@its.jnj.com
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Hsia
authors.forename: Neil
authors.initials: N
authors.lastname: Schluger
authors.forename: John J
authors.initials: JJ
authors.lastname: Cush
authors.forename: Richard E
authors.initials: RE
authors.lastname: Chaisson
authors.forename: Eric L
authors.initials: EL
authors.lastname: Matteson
authors.forename: Stephen
authors.initials: S
authors.lastname: Xu
authors.forename: Anna
authors.initials: A
authors.lastname: Beutler
authors.forename: Mittie K
authors.initials: MK
authors.lastname: Doyle
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hsu
authors.forename: Mahboob U
authors.initials: MU
authors.lastname: Rahman
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity; D013167:Spondylitis, Ankylosing / Q000188:drug therapy*; D014374:Tuberculin Test; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab