Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The advent of immunobiologic therapy with TNF inhibitors agents, has been associated with a significant increase in incident cases of tuberculosis in this population.


To estimate the incidence of tuberculosis in patients receiving TNF inhibitors therapy for rheumatic diseases. As secondary objectives, we sought to evaluate mortality and the clinical impact of screening for latent tuberculosis infection.


This retrospective study included patients with rheumatic diseases of Public Health System from the Brazilian state, a high TB incidence area, who received prescriptions of TNF inhibitors agents between 2006 and 2016.


A total of 5853 rheumatic disease patients were included. Patients were predominantly women (68.7%) aged 49.5 (± 14.7) years old. Forty-three cases of TB were found (2.86 cases per 1000 person-years; 18 times higher than in the general population). Adalimumab and certolizumab users presented a higher risk for TB development compared to etanercept users (RR: 3.11, 95%CI 1.16–8.35; 7.47, 95%CI 1.39–40.0, respectively). In a subgroup of patients, screening for latent tuberculosis infection was performed in 86% of patients, and 30.2% had a positive tuberculin skin test. Despite latent TB treatment, TB was diagnosed in 2 out of 74 (2.7%) patients. Overall, TB diagnosis did not increase mortality.


In this population-based study of rheumatic disease patients from a high incident area, TNF inhibitor exposure was associated with an 18-time increased TB incidence. Adalimumab and certolizumab were associated with greater and earlier TB diagnosis compared to etanercept.


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Citation: Sartori NS, Picon P, Papke A, Neyeloff JL, da Silva Chakr RM (2019) A population-based study of tuberculosis incidence among rheumatic disease patients under anti-TNF treatment. PLoS ONE 14(12): e0224963. https://doi.org/10.1371/journal.pone.0224963

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