Published online Nov 28, 2020. doi: 10.3748/wjg.v26.i44.6993
Peer-review started: July 21, 2020
First decision: October 18, 2020
Revised: November 5, 2020
Accepted: November 14, 2020
Article in press: November 14, 2020
Published online: November 28, 2020
Tuberculosis is a highly prevalent disease in Brazil, which is also seeing an increase in the incidence of inflammatory bowel diseases. Biological therapy improves quality of life but increases the risk of tuberculosis. This report is the first study in Latin America to relate the risk of developing tuberculosis in patients with inflammatory bowel disease under treatment.
The motivation was the lack of knowledge about the risk of developing tuberculosis in inflammatory bowel disease patients, especially patients using immunosuppressants and biologicals. The identification of active tuberculosis (TB) risk and how to prevent it is essential to alert physicians to the need for infectious screening and maintenance of care throughout the treatment.
The main objective was to identify the risk of developing active tuberculosis in inflammatory bowel disease patients under treatment. Knowledge of this risk will benefit the care of the patient before starting immunosuppressive and biological therapy and encourage surveillance throughout the treatment.
This study was a retrospective cohort study of inflammatory bowel disease (IBD) patients followed at a referral center in Salvador, Bahia, Brazil. A standardized, structured questionnaire was used for each patient in a direct interview, and medical records were reviewed. The cohort baseline was defined as the start of drug therapy directed at inflammatory bowel disease. Patients in this cohort were screened for latent TB using the tuberculin skin test before starting immunosuppressive or immunobiological therapy. The gross relative risk of developing active TB in patients treated with anti-tumor necrosis factor alpha (TNFα), azathioprine and anti-TNFα in combination with azathioprine compared to other treatments was obtained with the respective 95%CI. The adjusted relative risk for age, sex, type of IBD and latent TB was calculated using Poisson regression with robust variance (sex-model 1; sex and type of IBD-model 2; sex, type of IBD, latent TB-model 3; and sex, age, type of IBD, latent tuberculosis-model 4).
Immunosuppressive therapy, specifically azathioprine, anti-TNFα and the combination of these two drugs, were associated with a higher risk of active tuberculosis, with RRs of 5.85 (95%CI: 1.20-28.48), 3.93 (95%CI: 1.01-15.29) and 9.03 (95%CI: 2.38-34.28), respectively. When adjusted for sex, age, type of IBD and latent TB, anti-TNFα combined with azathioprine consistently increased the relative risk to 17.8 times more than conventional treatment (95%CI: 5.91-53.67; P < 0.001). Azathioprine was not affected by other variables, but infliximab presented a higher risk when adjusted for age, gender, latent tuberculosis and the type of inflammatory bowel disease.
Azathioprine and anti-TNF agents as monotherapy or in combination increased the risk of developing tuberculosis in inflammatory bowel disease patients. We reinforce that screening for latent tuberculosis should also be performed routinely in patients who start azathioprine.
A prospective study that monitors the evolution of IBD patients under treatment should be performed to identify possible variables that reduce the risk of developing active tuberculosis during treatment.