Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study

Antoni Noguera-Julian, Joan Calzada-Hernandez, Folke Brinkmann, Robindra Basu Roy, Olga Bilogortseva, Michael Buettcher, Isabel Carvalho, Vira Chechenyeva, Lola Falcon, Florian Goetzinger, Carmelo Guerrero-Laleona, Peter Hoffmann, Marija Jelusic, Tim Niehues, Iveta Ozere, Fiona Shackley, Elena Suciliene, Steven B Welch, Elisabeth H Scholvinck, Nicole RitzMarc Tebruegge

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

BACKGROUND: In adults, anti-tumor-necrosis-factor (TNF)-α therapy is associated with progression of latent tuberculosis infection (LTBI) to tuberculosis (TB) disease. The existing paediatric data are very limited.

METHODS: Retrospective multi-centre study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti-TNF-α therapy.

RESULTS: Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified; Crohn´s disease (n=8;42%) and juvenile idiopathic arthritis (n=6;32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-gamma release assay) was performed in 15 patients before commencing anti-TNF-α therapy, but only identified one LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti-TNF-α therapy and TB diagnosis was 13.1 (IQR:7.1-20.3) months. All cases presented with severe disease, predominately miliary TB (n=14;78%). One case was diagnosed post-mortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR:46-66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae.

CONCLUSIONS: The data indicate that LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti-TNF-α therapy are prone to severe TB disease, and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low TB prevalence settings.

Original languageEnglish
Pages (from-to)2561-2569
JournalClinical Infectious Diseases
Volume71
Issue number10
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Tuberculosis
  • anti-TNF-alpha
  • children
  • miliary tuberculosis
  • reactivation

Field of Science

  • 3.3 Health sciences
  • 3.2 Clinical medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

Fingerprint

Dive into the research topics of 'Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study'. Together they form a unique fingerprint.

Cite this