There is an increased risk of tuberculosis, or reactivation of latent tuberculosis, during treatment with tumour necrosis factor alpha ( TNF-alpha ) inhibitors. Tuberculosis in patients receiving TNF-alpha inhibitors can be life-threatening, and deaths from tuberculosis have occurred in these patients.
TNF-alpha inhibitors are therefore contraindicated in patients with active tuberculosis or other severe infections.
Screen patients for active and latent tuberculosis before starting treatment with a TNF-alpha inhibitor. Monitor them closely for infectious diseases including tuberculosis before, during, and after treatment.
TNF-alpha inhibitors are a class of biological medicines that block the proinflammatory cytokine TNF-alpha. The TNF-alpha inhibitors authorised in the UK are Adalimumab, Certolizumab, Etanercept, Golimumab, and Infliximab.
TNF-alpha inhibitors are authorised for the treatment of inflammatory and autoimmune conditions, such as rheumatoid arthritis, ankylosing spondylitits, Crohn’s disease, ulcerative colitis, psoriasis, and psoriatic arthritis.
TNF-alpha plays an important role in inflammatory processes, and is involved in autoimmune diseases, and immune responses to infection. TNF-alpha inhibition increases susceptibility to infectious diseases, including tuberculosis, and increases the risk of reactivation of latent tuberculosis.
An increased risk of tuberculosis in patients treated with TNF-alpha inhibitors has been confirmed in large observational studies. Reports of tuberculosis, including fatalities, in patients treated with TNF-alpha inhibitors continue to be received via the Yellow Card Scheme.
In many cases extrapulmonary tuberculosis, presenting as either local or disseminated disease has been reported. In one recent case, a patient receiving a TNF-alpha inhibitor died from tuberculosis that had not been diagnosed.
Advice for healthcare professionals
TNF-alpha inhibitors are contraindicated in patients with active tuberculosis or other severe infections.
Pretreatment screening - Assess all patients for active and latent tuberculosis before starting treatment with a TNF-alpha inhibitor and record the results on the patient's alert card. This assessment should include a detailed medical history of possible previous contact with tuberculosis and any history of immunosuppressive therapy.
Tests that may be used to diagnose active and latent tuberculosis include: interferon-gamma release assay ( IGRA ); tuberculin skin test; chest radiograph.
Be aware of the risk of false-negative tuberculin skin-test results, especially in patients who are severely ill or immunocompromised.
Diagnosis of tuberculosis – a) Active infection: if active tuberculosis is diagnosed, do not start treatment with a TNF-alpha inhibitor; b) Latent infection: if latent tuberculosis is diagnosed, start treatment for this infection before treatment with a TNF-alpha inhibitor; if latent tuberculosis is suspected, consider antituberculous therapy before starting treatment with a TNF-alpha inhibitor.
Monitoring - Closely monitor patients for infectious diseases, including tuberculosis, before, during, and after treatment with a TNF-alpha inhibitor. ( Xagena )
Source: MHRA - Drug Safety Update volume 7 issue 9, 2014: A1