The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review

Eur J Clin Microbiol Infect Dis. 2023 Apr;42(4):413-422. doi: 10.1007/s10096-023-04564-2. Epub 2023 Feb 16.

Abstract

Paradoxical reaction (PR) and immune reconstitution inflammatory syndrome (IRIS) are common complications of tuberculosis treatment. Corticosteroids are first-line treatment for severe PR or IRIS, particularly neurological. We report four cases of severe PR or IRIS during tuberculosis treatment who required TNF-α antagonists, and identified 20 additional cases through literature review. They were 14 women and 10 men, with a median age of 36 years (interquartile range, 28-52). Twelve were immunocompromised before tuberculosis: untreated HIV infection (n=6), or immunosuppressive treatment (TNF-α antagonists, n=5; tacrolimus, n=1). Tuberculosis was mostly neuromeningeal (n=15), pulmonary (n=10), lymph node (n=6), and miliary (n=6), multi-susceptible in 23 cases. PR or IRIS started after a median time of 6 weeks (IQR, 4-9) following anti-tuberculosis treatment start, and consisted primarily of tuberculomas (n=11), cerebral vasculitis (n=8), and lymphadenitis (n=6). First-line treatment of PR or IRIS was high-dose corticosteroids in 23 cases. TNF-α antagonists were used as salvage treatment in all cases, with infliximab (n=17), thalidomide (n=6), and adalimumab (n=3). All patients improved, but 6 had neurological sequelae, and 4 had TNF-α antagonist-related severe adverse events. TNF-α antagonists are safe and effective as salvage or corticosteroid-sparing therapeutic for severe PR or IRIS during tuberculosis treatment.

Keywords: Immune reconstitution inflammatory syndrome; Infliximab; Paradoxical reaction; TNF-α antagonists; Tuberculosis.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Female
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Humans
  • Immune Reconstitution Inflammatory Syndrome* / complications
  • Immune Reconstitution Inflammatory Syndrome* / drug therapy
  • Male
  • Middle Aged
  • Tuberculosis* / complications
  • Tuberculosis* / drug therapy
  • Tumor Necrosis Factor Inhibitors* / therapeutic use

Substances

  • Adrenal Cortex Hormones
  • Tumor Necrosis Factor Inhibitors