What is the risk of extrapulmonary tuberculosis in a patient started on Tumor Necrosis Factor (TNF) inhibitors for sarcoidosis?

From the Guidelines

Patients with sarcoidosis who are starting TNF inhibitors should be screened for tuberculosis (TB) and treated for latent TB infection if detected, to prevent extrapulmonary TB reactivation, as the risk of TB reactivation is significantly increased with TNF inhibitor therapy, particularly with infliximab and adalimumab, as reported in studies such as 1 and 1. The recommended screening includes a tuberculin skin test (TST) or interferon-gamma release assay (IGRA), along with a chest X-ray.

• If latent TB is diagnosed, treatment with isoniazid 300mg daily for 9 months or rifampin 600mg daily for 4 months should be initiated at least 4 weeks before starting TNF inhibitors, as suggested by guidelines such as those outlined in 1 and 1.
• For patients with extrapulmonary TB who develop it while on TNF inhibitors, the standard treatment is a 4-drug regimen of isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months, followed by isoniazid and rifampin for an additional 4-7 months, with the total duration typically being 6-9 months depending on the site of infection, as recommended in 1 and 1. TNF inhibitors generally need to be temporarily discontinued during TB treatment, though they may be cautiously reintroduced after 2 months of effective TB therapy if clinically necessary, as noted in 1. This approach is critical because TNF-alpha plays an essential role in granuloma formation and maintenance, which contains TB infection, and TNF inhibitors can disrupt this protective mechanism, leading to TB dissemination, particularly to extrapulmonary sites such as lymph nodes, bones, joints, and the central nervous system.

From the FDA Drug Label

Patients treated with infliximab products are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, salmonellosis and tuberculosis have been reported with TNF-blockers

Tuberculosis Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving infliximab products, including patients who have previously received treatment for latent or active tuberculosis

Extrapulmonary tuberculosis risk in patients started on TNF inhibitors for sarcoidosis:

• Patients with sarcoidosis who are started on TNF inhibitors, such as infliximab, are at increased risk for developing serious infections, including extrapulmonary tuberculosis.
• The risk of tuberculosis, including extrapulmonary tuberculosis, should be evaluated before initiating therapy with TNF blockers.
• Patients should be tested for latent tuberculosis infection prior to initiating therapy with TNF blockers, and treatment of latent tuberculosis infection should be considered prior to therapy.
• Patients who develop a new infection during treatment with TNF blockers should be closely monitored, and tuberculosis should be strongly considered, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis 2, 2, 2.

From the Research

Extrapulmonary Tuberculosis in Patients Started on TNF Inhibitors for Sarcoidosis

• Extrapulmonary tuberculosis (TB) can affect various organs, including lymph nodes, pleura, bones, and others, and is more likely to occur in patients with immunosuppressive conditions, such as those taking TNF-alpha inhibitors 3.
• The diagnosis of extrapulmonary TB is challenging and often requires invasive procedures to obtain a sample for microbiological testing 3, 4.
• Treatment of extrapulmonary TB generally follows the same principles as pulmonary TB, with a two-month regimen of four drugs (rifampicin, isoniazide, pyrazinamide, and ethambuthol) followed by a four-month therapy with two drugs (rifampicin and isoniazide) 3.
• The duration of therapy may be extended in certain cases, such as tuberculous meningitis or skeletal dissemination 3.
• Patients with sarcoidosis may be treated with TNF inhibitors, such as infliximab or adalimumab, which have shown efficacy in improving symptoms and reducing steroid use 5.
• However, the use of TNF inhibitors may increase the risk of developing extrapulmonary TB, highlighting the need for careful monitoring and screening for TB in patients starting TNF inhibitor therapy 3, 5.