The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

Abstract

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB).Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-c release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis.Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-c release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.KEYWORDS: Interferon-c release assay, tuberculin skin test, tuberculosis, tumour necrosis factor T umour necrosis factor (TNF) and TNF receptors play a key role in mediating immune responses in acute and chronic inflammation [1][2][3]. Over the past decade, TNF antagonists in the form of anti-TNF monoclonal antibodies or TNF fusion protein have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis and psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis and inflammatory bowel disease [4][5][6][7]. Tuberculosis (TB) is a granulomatous disease caused by infection with Mycobacterium tuberculosis.Most of the individuals who are thought to have become infected with M. tuberculosis will never develop TB due to the control exercised by the host immune system [8,9]. One of the key cytokines in the immune response against infection with M. tuberculosis is TNF, which is also critical for the integrity of the granuloma [10]. Individuals who are being treated with anti-TNF therapies are at increased risk of developing TB. Following TNF antagonist therapy, the relative risk for TB is increased 1.6-25.1 times, depending on the clinical setting and the TNF antagonist used [4,7,11,12]. The majority of cases of TB related to TNF antagonist therapies occur in close temporal proximity to

Interferon- release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis

“…Clinical guidance for the diagnosis of LTBI is especially important for the care of immunocompromised individuals, e.g. patients undergoing tumour necrosis factor (TNF)-antagonists therapies [14], who carry an increased risk of progression to active tuberculosis. Several studies, and consequent systematic reviews and meta-analyses have been conducted evaluating IGRA accuracy in diagnosing LTBI [15][16][17][18].…”

Mycobacterial diseases developed during anti-tumour necrosis factor-α therapy

“…Most guidelines recommend temporary discontinuation of TNF-a antagonists when TB develops during anti-TNF-a therapy [30][31][32][33][34]. Whether TNF-a antagonists should be discontinued in patients who develop NTM lung disease during anti-TNF-a therapy remains a clinical issue.…”

IP-10 release assays in the diagnosis of tuberculosis infection: current status and future directions

“…The use of IGRAs and TST in screening for latent TB infection before initiation of immunosuppression with, for example, TNF-a inhibitors, and also that IGRAs are more specific and in some instances more sensitive than TST in this vulnerable group of patients is well recognized [76]. However, false-negative IGRA results occur, and test performance is impaired, in patients treated with prednisolone and possibly also other drugs used to treat inflammatory diseases [77].…”