A population-based study of tuberculosis incidence among rheumatic disease patients under anti-TNF treatment

Abstract

IntroductionTuberculosis (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.ObjectiveTo 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.MethodsThis 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.ResultsA 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.ConclusionIn 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.

The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics

“…General side effects of all TNF-α inhibitors involve headaches, rashes, anemia, transaminitis, infectious, and, most commonly, an injection site reaction through a subcutaneous route [ 90 , 91 ]. The worsening of heart failure and increased risk of developing tuberculosis as well as lymphoma are significantly observed in patients who have autoimmune diseases compared to healthy people [ 92 , 93 , 94 ]. Thus, it is recommended that all individuals be screened for these before beginning the treatment, and preventive therapy must be performed by priority if they are detected.…”

Management of Rheumatoid Arthritis: An Overview

“…The use of TNF-α inhibitors was associated with an 18-fold increased TB incidence in a population-based cohort investigation of RA patients from a high-incidence area. When compared to etanercept, adalimumab was linked to a higher and earlier diagnosis of TB [ 193 ]. Adalimumab-atto, adalimumab-adbm, adalimumab-adaz, adalimumab-bwwd, adalimumab-afzb and adalimumab-fkjp are biosimilars approved by the FDA for the treatment of RA [ 194 ].…”

The Potential for Repurposing Anti-TNF as a Therapy for the Treatment of COVID-19

“…71,72 Despite this, TB reactivation following anti-TNF therapy does not increase mortality, and there is widespread use of anti-TNF therapy in these regions. 73 Importantly, the risk for latent TB reactivation increases over time, with only 10% of the reactivation risk of long-term infliximab therapy incurred in the first month. Of note, etanercept confers a markedly lower overall risk for TB reactivation compared with other anti-TNF agents and an even smaller proportion of its risk in the first month of use, probably because of its reduced capacity for granuloma destabilization.…”