Tuberculosis despite latent infection screening and treatment in patients receiving TNF inhibitor therapy

Clin Rheumatol. 2021 Sep;40(9):3783-3788. doi: 10.1007/s10067-021-05697-5. Epub 2021 Mar 20.


Introduction: Although latent tuberculosis infection (LTBI) treatment is given before anti-tumor necrosis factor (TNF) treatment, tuberculosis (TB) still develops in these patients and the risk factors are not well known. Besides, there is little data on the safety of isoniazid (INH) treatment in this group of patients. This study aimed to determine the risk factors for the development of tuberculosis and the safety of LTBI in such patients.

Methods: All patients (n=665) given anti-TNF in a single center were included in this study. Complete data were obtained from the records of 389 patients.

Results: Seven patients (1.1%) were diagnosed with TB. There was no significant difference in age, gender, smoking rate, comorbidities, leukocyte counts, hemoglobin, creatinine, AST, ALT, protein levels, and tuberculin reaction between patients with and without TB. Of 389 patients, 289 (76%) had received INH prophylaxis, including 43 tuberculin-negative patients. Thirty patients had anti-TNF use prior to INH prophylaxis. None of these patients had TB in the follow-up period. Seven patients who developed TB had completed LTBI treatment, including one patient who was tuberculin-negative. The time from the completion of INH treatment to the diagnosis of TB was 6-61 months. None had any history of contact with TB during this period. INH treatment was associated with hepatotoxicity in 49 patients (17%); all resolved without any need to stop INH.

Conclusion: Patients on anti-TNF treatment had a high rate of TB despite INH prophylaxis, but no risk factor for TB development was identified. Mild hepatotoxicity frequently developed during LTBI treatment. Key Points • Tuberculosis still develops in patients treated with tumor necrosis factor (TNF)-inhibitors despite prior screening and treatment for latent tuberculosis infection (LTBI). • In this cohort, all patients in whom tuberculosis developed had been treated for LTBI and all but one were initially tuberculin-positive. No risk factors have been identified. • The current policy of treating tuberculin-positive patients with a 9-month INH regimen does not seem to be fully effective in preventing tuberculosis.

Keywords: Hepatotoxicity; Isoniazid; TNF inhibitor; Treatment; Tuberculosis.

MeSH terms

  • Antitubercular Agents / adverse effects
  • Humans
  • Isoniazid / adverse effects
  • Latent Infection*
  • Latent Tuberculosis* / diagnosis
  • Latent Tuberculosis* / drug therapy
  • Tuberculin Test
  • Tuberculosis*
  • Tumor Necrosis Factor Inhibitors


  • Antitubercular Agents
  • Tumor Necrosis Factor Inhibitors
  • Isoniazid