CDC Issues Guidance on New Treatment Option for TB

The CDC has released recommendations on how to administer a new 12-dose regimen for preventive therapy that will significantly shorten and simplify the course of treatment for latent tuberculosis (TB) infection from about 9 months to 12 weeks. The guidelines, which are published in the December 9, 2011 issue of the Morbidity and Mortality Weekly Report (MMWR), are based on the results of 3 clinical trials, as well as expert opinion.

The recommendations follow results from a large clinical trial published last week in the New England Journal of Medicine which found that a once-weekly regimen of the anti-TB drugs rifapentine and isoniazid taken over a period of 3 months was as effective in preventing TB disease as the standard self-administered 9-month daily regimen of isoniazid alone, and was completed by more patients. The new regimen has a significant benefit over the previous standard of treatment by cutting the doses required from 270 daily doses to 12 once-weekly doses.

“This regimen has the potential to be a game-changer in the United States when it comes to fighting TB,” said CDC Director Thomas R. Frieden, MD, MPH. “It gives us a new, effective option that will reduce by two-thirds—from 9 months to 3 months—the length of time someone needs to take medicine to prevent latent TB infection from progressing to active TB disease.”

Latent TB infection occurs when an individual has TB bacteria but does not have symptoms and cannot transmit the bacteria to others. If the bacteria become active, the person will develop TB disease, become sick, and may spread the disease to others. Although not all patients with latent TB infection will develop TB disease, some patients, such as those with weakened immune systems, are at higher risk of progression. Many of those at high risk of developing TB disease never even begin the 9-month course of standard treatment, and among those who do, many don’t complete it.

In the United States, the number of individuals with TB disease has decreased significantly. However, approximately 4% of the US population are infected with the TB bacterium.

“If we are going to achieve our goal of TB elimination in the United States, we must ensure that those with latent TB infection receive appropriate evaluation and treatment to prevent their infection from progressing to TB disease and possibly spreading to others,” said Kevin Fenton, MD, of the CDC, in a statement. “It is critical that we accelerate progress against TB in the United States in order to avoid a resurgence of the disease.”

The new 12-dose regimen adds another effective treatment option to the prevention toolkit for TB, and is not meant to replace other preventative treatment regimens for all patients where the new regimen is not the best option. Major components of the recommendations for this regimen include:

• Provision of 12 once-weekly doses via directly observed therapy: The new regimen consists of 12 once-weekly doses of rifapentine and isoniazid. Doses should be taken under the supervision of a health care provider to ensure completion of doses and to allow for monitoring of safety among patients. Clinicians should rule out TB disease among all patients before beginning the 2-drug regimen.
• The regimen is recommended for otherwise healthy individuals aged 12 and older who are at high risk for developing TB disease. This includes anyone who has had recent exposure to contagious TB, conversion from negative to positive on a test for TB infection, or a chest X-ray indicating prior TB disease. Those living with HIV who are otherwise healthy and not taking antiretrovirals may also use this regimen if TB preventive treatment is indicated.
• Because the safety of the regimen for some patients is unknown, it is not recommended for use among children under the age of 2, women who are pregnant or planning to become pregnant, and HIV-infected individuals taking antiretrovirals. Patients whose TB infection is presumed to be the result of exposure to a person with TB disease that is resistant to one of the two drugs should not receive this regimen.
• Monitoring for adverse events is critical. Health care workers supervising patients who are taking the drugs should educate patients and monitor for possible adverse effects, and report any problems to a clinician. Patients should undergo a clinical assessment at least monthly.

CDC is also assessing whether self-administered use of the 12-dose regimen is feasible and will result in similar levels of adherence.