What is the relationship between Latent Tuberculosis (LTB) and biologics?

From the Guidelines

Latent tuberculosis (LTb) infection should be screened for and treated before starting biologic therapy, particularly TNF inhibitors, due to the increased risk of TB reactivation, as stated in the ECCO guidelines 1. The risk of reactivation is increased in patients treated with biologics or JAK inhibitors, and the disease can be more severe than in the background population 1.

Screening and Treatment Approach

• Screening typically involves a tuberculin skin test (TST) or interferon-gamma release assay (IGRA) along with chest X-ray and risk assessment.
• If LTb is detected, treatment should be initiated at least 4 weeks before starting biologics, as recommended in the ECCO guidelines 1.
• The preferred regimen is isoniazid 300mg daily for 6-9 months, though shorter alternatives include rifampin 600mg daily for 4 months or isoniazid plus rifapentine weekly for 3 months.

Special Considerations

• For patients already on biologics who develop LTb, the biologic should be temporarily discontinued while TB treatment is initiated.
• TNF inhibitors pose the highest risk for TB reactivation, while IL-12/23 inhibitors, IL-17 inhibitors, and JAK inhibitors carry lower risks.
• Re-screening patients previously exposed to biologics and JAK inhibitors before switch or swap, and under special conditions, re-screening during anti-TNF agent therapy and JAK inhibitors should be considered, as recommended in the ECCO guidelines 1.

From the FDA Drug Label

Patients treated with Enbrel 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, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis have been reported with TNF-blockers. Patients have frequently presented with disseminated rather than localized disease Treatment with Enbrel should not be initiated in patients with an active infection, including clinically important localized infections.

The FDA drug label does not answer the question about LTb and biologics.

From the Research

LTb and Biologics

• The use of biologics such as adalimumab, etanercept, and infliximab in the treatment of rheumatoid arthritis (RA) has been extensively studied 2, 3, 4.
• These biologics have been shown to be effective in reducing the symptoms and signs of RA, improving physical function, and slowing radiographic changes in joints 2, 4.
• The cost-effectiveness of these biologics has also been evaluated, with results suggesting that they are most cost-effective when used as last active therapy 2.
• The risk of adverse events, including serious infections and lymphoma, has been associated with the use of biologics in RA patients 5, 6.
• A meta-analysis of 21 randomized, placebo-controlled trials found that etanercept and adalimumab had higher efficacy results with short-term treatment, while adalimumab appeared to be the most effective with long-term treatment 4.

Efficacy of Biologics

• Adalimumab, etanercept, and infliximab have been shown to be effective in reducing the symptoms and signs of RA, with response rates ranging from 20% to 70% 2, 4.
• The combination of a biologic with methotrexate has been shown to be more effective than methotrexate alone in patients with early RA 2.
• The efficacy of biologics has been evaluated in various patient populations, including those who are naive to methotrexate and those who have failed previous disease-modifying antirheumatic drug (DMARD) therapy 3.

Safety of Biologics

• The use of biologics has been associated with an increased risk of serious infections, including tuberculosis and lymphoma 5, 6.
• The risk of adverse events has been evaluated in various studies, with results suggesting that the risk is higher with the use of biologics compared to traditional DMARDs 5.
• Risk mitigation strategies have been identified and implemented to minimize the risk of adverse events associated with biologic therapy 6.