Short latent TB therapy matches standard care

In a Bayesian network meta-analysis, some of the rifamycin-containing regimens also were less likely to cause liver damage than standard therapy with isoniazid (Nydrazid), according to Helen Stagg, PhD, of University College London, and colleagues.

Such regimens might become "effective alternatives to isoniazid monotherapy," Stagg and colleagues reported online in Annals of Internal Medicine.

While 9 months of isoniazid -- the standard in the U.S. -- is efficacious at preventing latent TB from becoming active, the regimen's length means many patients do not complete therapy, the researchers noted.

In addition, isoniazid is associated with a risk of hepatotoxicity that can be fatal.

For those reasons, there has been increased interest in finding shorter regimens containing rifamycin derivatives, such as rifampin (Rifadin), rifapentine (Priftin), and rifabutin (Mycobutin).

"Effective treatment of latent tuberculosis infection is an important component of tuberculosis elimination programs," Stagg and colleagues noted.

While new regimens are promising, few can be directly compared, they reported. Most studies have involved conventional meta-analyses, which are "severely limited in the inferences they could make about relative efficacy and toxicity," they wrote.

To help fill the gap, they turned to Bayesian hierarchical models, whose network approach allows indirect comparisons "and thus produces inferences of relative efficacy that would not otherwise be possible," Stagg and colleagues reported.

The raw material for the analysis was 53 randomized, controlled trials that evaluated treatment for latent TB and reported at least one of two endpoints -- preventing active TB or hepatotoxicity.

Fifteen regimens were available, leading to 105 possible comparisons of which 42 were compared directly in the studies.

The analysis showed that, compared with placebo, several regimens were efficacious:

• Isoniazid for 6 months or 12 months and longer had odds ratios for active TB of 0.64 and 0.52, respectively.
• Rifampin for 3 to 4 months had an OR for active TB of 0.41.
• Rifapentine and isoniazid and rifampin-isoniazid were also efficacious with ORs of 0.61 and 0.52, respectively.

When the researchers ranked the regimens, rifampin alone or with isoniazid for 3 to 4 months seemed to be particularly efficacious, although they cautioned the finding is based on limited data.

Data on hepatotoxicity was sparse, they reported, but analysis based on direct comparisons suggested that rifampin alone or with isoniazid was less toxic than isoniazid alone for 6, 9, or 12 to 72 months.

The analysis contains "two useful and important messages," commented Dick Menzies, MD, of the Montreal Chest Institute in Montreal and Timothy Sterling, MD, of Vanderbilt University School of Medicine in Nashville, Tenn.

The first is that evidence accumulating over the past 20 years shows clearly that short courses of rifamycin-containing regimens work as well and are safer than those based on isoniazid, they argued in an accompanying editorial.

"Surely, it is time to get a move on -- away from (isoniazid) as our primary therapy and toward regimens containing rifamycin," they wrote.

For patients, the "considerable" advantages include greater safety and better protection against TB, while for TB programs, shorter treatment courses potentially could mean lower workloads and costs.

The second message -- which rifamycin-containing regimen physicians should choose -- is less clear, they noted.

For instance, the regimen that had the best combined rankings (efficacy and lack of hepatotoxicity) was rifampin for 3 or 4 months, but the efficacy result was based on a single 3-month trial.

"Further trials are needed to clarify which of these short-course regimens offer the greatest advantages for patients and programs and under what conditions," Menzies and Sterling concluded.

Stagg and colleagues cautioned that the risk of bias was unclear in many of the studies, and there was limited data for many comparisons, especially those concerning liver toxicity.

Stagg and some co-authors disclosed financial support from the U.K. National Institute for Health Research.

Stagg disclosed relevant relationships with Otsuka Pharmaceutical and Sanofi. Other co-authors disclosed no relevant relationships with industry.

A co-author disclosed a relevant relationship with the World Health Organization (WHO). Another co-author disclosed serving on the WHO Latent Tuberculosis Guideline Development Group, serving as chair of the U.K. National Institute for Health and Care Excellence Tuberculosis Guideline Development Group, and serving as head of the Tuberculosis Section at Public Health England.

Primary source: Annals of Internal Medicine
Source reference: Stagg HR, et al "Treatment of latent tuberculosis: A network meta-analysis" Ann Intern Med 2014.

Source: MedPage Today