Risk of Tuberculosis in Patients Treated With TNF Antagonists
Risk of Tuberculosis in Patients Treated With TNF Antagonists
Over the last 12 years, TNF antagonists have been successfully used for the treatment of numerous patients afflicted by chronic inflammatory disorders. However, data from clinical trials and registries have shown that patients treated with these biologics have an increased risk of reactivating latent TB. The fact that TNF plays a role in the immune cell response and, more specifically, in maintenance of granuloma integrity is the accepted grounds for reactivation of TB following inhibition of TNF. Appropriate screening of latent TB and proper management of cases substantially reduces the incidence of active TB. Nevertheless, debate still remains regarding the value of the tuberculin skin test and IFN-γ-release assays as diagnostic tools, and treatment across guidelines and recommendations. This largely reflects differences in background population.
TNF is a ubiquitous cytokine involved in mechanisms that form part of the host response to infection and cancer. It also has a critical role in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis and inflammatory bowel disease.
Over the last 12 years, TNF antagonists have been successfully used for the treatment of chronic inflammatory diseases. Noticeably, data from clinical trials and clinical observation show an increased risk of non-opportunistic intracellular infections and opportunistic infections associated with TNF antagonist use, with TB being one of the most difficult to manage.Mycobacterium tuberculosis infection is commonplace; the bacteria causes a granulomatous disease, however, most individuals infected with M. tuberculosis will never develop TB owing to elimination or containment of the bacteria by host immune mechanisms. The role of TNF in this immune response, particularly against intracellular bacteria and maintenance of the granuloma integrity, explains the mechanism of reactivation of latent granulomatous diseases following the inhibition of TNF. Thus, appropriate screening and management of latent TB is crucial for patients undergoing TNF antagonists treatment. At present, there is a shortage of evidence to support either the best screening method for latent infection or the best regimen for latent TB. Therefore, clinical decisions are merely supported by expert recommendations such as the recently published Tuberculosis Network European Trials Group (TBNET) consensus statement. The current knowledge of TB disease in patients treated with TNF antagonist will be reviewed in this article.
Abstract and Introduction
Abstract
Over the last 12 years, TNF antagonists have been successfully used for the treatment of numerous patients afflicted by chronic inflammatory disorders. However, data from clinical trials and registries have shown that patients treated with these biologics have an increased risk of reactivating latent TB. The fact that TNF plays a role in the immune cell response and, more specifically, in maintenance of granuloma integrity is the accepted grounds for reactivation of TB following inhibition of TNF. Appropriate screening of latent TB and proper management of cases substantially reduces the incidence of active TB. Nevertheless, debate still remains regarding the value of the tuberculin skin test and IFN-γ-release assays as diagnostic tools, and treatment across guidelines and recommendations. This largely reflects differences in background population.
Introduction
TNF is a ubiquitous cytokine involved in mechanisms that form part of the host response to infection and cancer. It also has a critical role in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis and inflammatory bowel disease.
Over the last 12 years, TNF antagonists have been successfully used for the treatment of chronic inflammatory diseases. Noticeably, data from clinical trials and clinical observation show an increased risk of non-opportunistic intracellular infections and opportunistic infections associated with TNF antagonist use, with TB being one of the most difficult to manage.Mycobacterium tuberculosis infection is commonplace; the bacteria causes a granulomatous disease, however, most individuals infected with M. tuberculosis will never develop TB owing to elimination or containment of the bacteria by host immune mechanisms. The role of TNF in this immune response, particularly against intracellular bacteria and maintenance of the granuloma integrity, explains the mechanism of reactivation of latent granulomatous diseases following the inhibition of TNF. Thus, appropriate screening and management of latent TB is crucial for patients undergoing TNF antagonists treatment. At present, there is a shortage of evidence to support either the best screening method for latent infection or the best regimen for latent TB. Therefore, clinical decisions are merely supported by expert recommendations such as the recently published Tuberculosis Network European Trials Group (TBNET) consensus statement. The current knowledge of TB disease in patients treated with TNF antagonist will be reviewed in this article.
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