Treatment-based risk stratification of infections in inflammatory bowel disease: A comparison between anti-tumor necrosis factor-α and nonbiological exposure in real-world setting

J Gastroenterol Hepatol. 2021 Jul;36(7):1859-1868. doi: 10.1111/jgh.15367. Epub 2020 Dec 25.


Background and aim: Infective issues about anti-tumor necrosis factor (TNF)-α agents in inflammatory bowel disease (IBD) remain controversial, especially when compared with nonbiological treatments. This study aimed to evaluate the incidence and prevalence of several infections in anti-TNF-α-exposed patients compared with nonbiological treatments.

Methods: All naïve IBD subjects treated with anti-TNF-α and matched nonbiologic-exposed patients were included.

Results: Among 3453 patients in the database, 288 anti-TNF-α-exposed subjects and 288 nonbiologic-exposed IBD controls met inclusion criteria. Fifty-eight infections (20.1%) occurred during anti-TNF-α treatment versus 23 (8%) in the matched group (odds ratio [OR] 2.9, P < 0.001) (incidence 5.72 vs 0.96/100 patient-years, incidence ratio [IR] 6, P < 0.001). IR was higher for anti-TNF-α versus mesalamine/sulfasalazine (IR 40.8, P < 0.001), similar to azathioprine/6-mercaptopurine/methotrexate (IR 0.78, P = 0.32) and lower than corticosteroids (IR 0.05, P < 0.001). The incidence rate of serious infections was 1.3 in the anti-TNF-α-exposed versus 0.38/100 patient-years in nonexposed subjects (IR 3.44, P = 0.002), without significant difference between anti-TNF-α and azathioprine/6-mercaptopurine/methotrexate (1.3 vs 3.03/100 patient-years, IR 0.43, P = 0.1). Predictors of infections in anti-TNF-α-exposed patients were concomitant use of systemic steroids (OR 1.9, P = 0.02) or azathioprine (OR 2.6, P = 0.01) and a body mass index < 18.5 at time of infection (OR 2.2, P = 0.01).

Conclusions: The risk of developing infections during anti-TNF-α therapy remains high, although not dissimilar to that found for other immunosuppressants, while concomitant immunosuppression and malnutrition appear the most important causes of infection.

Keywords: Anti-TNF-α; Infections; Inflammatory bowel disease; Safety.

MeSH terms

  • Azathioprine / adverse effects
  • Colitis*
  • Humans
  • Inflammatory Bowel Diseases* / drug therapy
  • Inflammatory Bowel Diseases* / epidemiology
  • Mercaptopurine
  • Methotrexate / adverse effects
  • Risk Assessment
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha / metabolism


  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha
  • Mercaptopurine
  • Azathioprine
  • Methotrexate