New guidelines offer more nuances, treatment options

Extended therapy counseled for some

New TB treatment guidelines due out early next year will recommend lengthening treatment by an extra two to three months for patients who are still sputum-culture positive after two months’ treatment.

For HIV-negative patients without cavitary disease, the new guidelines will also give the go-ahead to streamlining the continuation phase of treatment by substituting once-weekly rifapentine (RPT) and isoniazid (INH) for twice-weekly INH and rifampin (RIF).

Together, the two additions will provide a more nuanced approach to TB treatment, says Rick O’Brien, MD, chief of the research and evaluation branch of the Division of TB Elimination at the Centers for Disease Control and Prevention in Atlanta.

"That’s probably the most important thing about this new treatment statement: the way it stratifies treatment based on patient characteristics," O’Brien says.

The last comprehensive treatment guidelines for adults and children date back to 1994. Like the older document, the new one was developed mainly by TB experts at the CDC working with their counterparts at the American Thoracic Society in New York City.

A handful of other professional organizations also supplied input, and for the first time, the Infectious Disease Society of America served as a co-sponsor of the new document. The guidelines are nearing final-draft form and should be completed by early winter. They will be published first in the American Journal of Respiratory Care and Critical Medicine, O’Brien adds.

In a recent meeting of the Advisory Committee to Eliminate Tuberculosis (ACET), O’Brien explained how data from Study 22 supported both the decision to recommend more therapy in some cases and the decision to allow a streamlined version in others.

Study 22 was the TB Trial Consortium’s clinical trial of rifapentine, a derivative of rifamycin with a half-life five times longer than that of rifampin. (The consortium is an agency at the CDC that conducts trials on promising TB drug candidates.)

As hoped, the study found that among patients with no radiographic evidence of cavitary disease, once-weekly RPT and INH were as safe, and almost as effective in preventing relapse or treatment failure, as twice-weekly RIF and INH. Across the United States, about 45% of patients
fit the non-cavitary-disease category, CDC TB experts say.

In addition, the study turned up some unexpected findings. The 20% or so of patients in the study who were still sputum culture-positive after two months of therapy tended to have problems with both the experimental RPT/INH regimen and the standard twice-weekly regimen of INH and RIF. This means there were finally enough data to clinch what had been a long-standing hunch among experienced clinicians.

Then, O’Brien told his audience at ACET, CDC researchers went back and considered data from a much older study, a Hong Kong trial of patients afflicted with both TB and silicosis. Silicosis, a disabling lung condition related to exposure to industrial contaminants, impairs pulmonary immunity, making effective TB treatment much more difficult.

To determine whether longer treatment would help, the Hong Kong researchers gave six months of anti-TB treatment to one group of patients and eight months of treatment to the other. The two extra months of treatment resulted in much better outcomes. That suggested to CDC experts that two or three more months will probably work to reduce rates of relapse and failure in the sputum-culture positive group to acceptable levels.

Other new points in the forthcoming guidelines are expected to include:

• additional emphasis on the public-health dimension of TB treatment;

• discussions of the role of the fluoroquinolones in treating drug-resistant disease;

• detailed discussions of drug interactions and rifabutin’s role in the treatment of HIV-positive TB patients;

• stronger recommendations for use of fixed-dose combination drugs;

• stronger emphasis on the use of directly observed therapy as an initial management