FROM annals of internal medicine

Latent tuberculosis infection can be safely and effectively treated with 3- and 4-month medication regimens, including those using once-weekly dosing, according to results from a new meta-analysis.

The findings, published online July 31 in Annals of Internal Medicine, bolster evidence that shorter antibiotic regimens using rifamycins alone or in combination with other drugs are a viable alternative to the longer courses ( Ann Intern Med. 2017;167:248-55 ).

While the new study looked at efficacy and toxicity across treatment strategies only and found no significant differences between shorter rifamycin-based regimens and isoniazid-based regimens lasting 6 months or longer, short courses are considered likely to see better patient adherence, previous research in latent TB has indicated ( BMC Infect Dis. 2016;16:257 ).

For their research, Dominik Zenner, MD , an epidemiologist with Public Health England in London, and his colleagues updated a meta-analysis they published in 2014. The team added 8 new randomized studies to the 53 that had been included in the earlier paper ( Ann Intern Med. 2014 Sep;161:419-28 ).

Using pairwise comparisons and a Bayesian network analysis, Dr. Zenner and his colleagues found comparable efficacy among isoniazid regimens of 6 months or more; rifampicin-isoniazid regimens of 3 or 4 months, rifampicin-only regimens, and rifampicin-pyrazinamide regimens, compared with placebo (P less than .05 for all).

Importantly, a rifapentine-based regimen in which patients took a weekly dose for 12 weeks was as effective as the others.

“We think that you can get away with shorter regimens,” Dr. Zenner said in an interview. Although 3- to 4-month courses are already recommended in some countries, including the United Kingdom, for most patients with latent TB, “clinicians in some settings have been quite slow to adopt them,” he said.

The U.S. Centers for Disease Control and Prevention currently recommend multiple treatment strategies for latent TB, depending on patient characteristics. These include 6 or 9 months of isoniazid; 3 months of once-weekly isoniazid and rifapentine; or 4 months of daily rifampin.

In the meta-analysis, rifamycin-only regimens performed as well as did those regimens that also used isoniazid, the study showed, suggesting that, for most patients who can safely be treated with rifamycins, “there is no added gain of using isoniazid,” Dr. Zenner said.

He noted that the longer isoniazid-alone regimens are nonetheless effective and appropriate for some, including people who might have potential drug interactions, such as HIV patients taking antiretroviral medications.

About 2 billion people worldwide are estimated to have latent TB, and most will not go on to develop active TB. However, because latent TB acts as the reservoir for active TB, screening of high-risk groups and close contacts of TB patients and treating latent infections is a public health priority.

But many of these asymptomatic patients will get lost between a positive screen result and successful treatment completion, Dr. Zenner said.

“We have huge drop-offs in the cascade of treatment, and treatment completion is one of the worries,” he said. “Whether it makes a huge difference in compliance to take only 12 doses is not sufficiently studied, but it does make a lot of sense. By reducing the pill burden, as we call it, we think that we will see quite good adherence rates – but that’s a subject of further detailed study.”

The investigators noted as a limitation of their study that hepatotoxicity outcomes were not available for all studies and that some of the included trials had a potential for bias. They did not see statistically significant differences in treatment efficacy between regimens in HIV-positive and HIV-negative patients, but noted in their analysis that “efficacy may have been weaker in HIV-positive populations.”

The U.K. National Institute for Health Research provided some funding for Dr. Zenner and his colleagues’ study. One coauthor, Helen Stagg, PhD, reported nonfinancial support from Sanofi during the study, and financial support from Otsuka for unrelated work.


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