Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America
Flora Maria Lorenzo Fortes, Ney Boa Sorte, Victor D Mariano, Laíla D Andrade, Fernanda A Oliveira, Monique CA Santos, Cláudia Ivanilda N dos Santos, Catharina A Passos, Mila P Pacheco, Valdiana C Surlo, Neogélia P de Almeida, Jaciane AM Fontes, Andréa M Pimentel, Raquel Rocha, Genoile Oliveira Santana
Flora Maria Lorenzo Fortes, Ney Boa Sorte, Mila P Pacheco, Genoile Oliveira Santana, Pharmaceutical Sciences Pos-graduation Program, State University of Bahia, Salvador, BA 40460-120, Brazil
Flora Maria Lorenzo Fortes, Valdiana C Surlo, Neogélia P de Almeida, Jaciane AM Fontes, Andréa M Pimentel, Outpatient Gastroenterology Unit, General Hospital Roberto Santos, Salvador, BA 40286-901, Brazil
Ney Boa Sorte, Victor D Mariano, Fernanda A Oliveira, Monique CA Santos, Cláudia Ivanilda N dos Santos, Catharina A Passos, Life Sciences Department, State University of Bahia, Salvador, BA 41150-000, Brazil
Laíla D Andrade, Department of Medicine, FTC University, Salvador, BA 41741-590, Brazil
Raquel Rocha, Department of Sciences of Nutrition, School of Nutrition, Federal University of Bahia, Salvador, BA 41701-035, Brazil
Author contributions: Fortes FML was contributed to study design, patient identification, data collection, statistical analysis, drafting of the manuscript; Boa Sorte N was contributed to statistical analysis; Mariano VD, Andrade LD, Oliveira FA, Santos MCA, dos Santos CIN, Passos CA, Surlo VC, de Almeida NP, Fontes JAM and Pimentel AM were contributed to patient identification, data collection; Rocha R and Pacheco MP were contributed to manuscript review, technical or material support; Santana GO was contributed to study design, manuscript revision, supervision of the study and full access to all of the data in the study, responsible for the integrity of the data.
Institutional review board statement: The Roberto Santos General Hospital Research Ethics Committee approved this research under the opinion number 1935.651/2017. The patients signed the Informed Consent Term before any procedure.
Informed consent statement: All study participants identities were anonymized and details that might disclose their identities were omitted. For this type of study formal consent is not required.
Conflict-of-interest statement: Genoile O Santana: Advisory board–Janssen; Speaker–Abbvie, Ferring, Janssen, Takeda and UCB Pharma; Research–Janssen, Lilly, Pfizer, Roche and Takeda. The other authors declare that they have no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author atraquelrocha2@yahoo.com.br. Participants gave informed consent for data sharing.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Raquel Rocha, DSc, MSc, Assistant Professor, Department of Sciences of Nutrition, School of Nutrition, Federal University of Bahia, Avenida Araújo Pinho, 32, Canela, Salvador, BA 41701-035, Brazil. raquelrocha2@yahoo.com.br
Received: July 21, 2020
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
ARTICLE HIGHLIGHTS
Research background
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.
Research motivation
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.
Research objectives
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.
Research methods
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).
Research results
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.
Research conclusions
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.
Research perspectives
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.
