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TB could be cured by four months’ treatment in many patients

Standard six-month drug regimen for pulmonary tuberculosis risks both over- and under-treatment

Louise Prime

Tuesday, 06 November 2018

Pulmonary tuberculosis (TB) can be cured with just four months’ drug treatment in patients with minimal disease, but six months is too short a treatment duration to cure infection in the moderate or severe disease categories, a new analysis has shown. The authors of the study*, published in Nature Medicine, said they had shown that the standard six-month treatment programme risks both over- and under-treatment in different patient groups – and also that a stratified medicine approach can be feasibly applied to achieve treatment shortening for many patients with TB.

The study authors pointed out that TB now kills more people worldwide than any other infectious disease – about 1.3 million a year – and several previous studies have looked at the efficacy of different drug treatment regimens. They said that although three ‘pivotal’ trials of four-month treatments had failed to demonstrate non-inferiority compared with the standard six-month duration, they believed that this was because all patients were treated similarly, taking no account of their disease severity; overall, about four-fifths of all participants were cured.

So, funded in part by the World Health Organization and the Bill & Melinda Gates Foundation, they re-analysed the original patient-level data from these trials, stratifying the 3,405 participants into minimal, moderate and severe disease categories. They reported that four-month regimens were highly effective in the 47% of participants who had minimal disease (defined by <2+ sputum smear grade or non-cavitary disease), whereas a hard-to-treat phenotype, defined by high smear grades and cavitation, might require treatment durations of even longer than six months to cure all.

They found several risk factors associated with unfavourable outcome, including a baseline smear grade of 3+ relative to <2+; HIV seropositivity; and treatment adherence of 90% or less, which resulted in a fivefold greater risk of treatment failure. They noted that this last factor goes against the assumption built into US and international TB treatment guidelines that it was safe to miss occasional drug doses, and commented: “People thought it was OK to miss some doses. But it’s not OK to miss even one out of 10 doses.”

They concluded: “Our study shows a stratified medicine approach can be feasibly applied to achieve treatment shortening for many patients with TB. A one-size-fits-all approach leads to undertreatment of patients with severe forms of disease, and overtreatment, with the potential that the drugs will cause harm, for patients who have less extensive disease.”

*Imperial MZ, Nahid P, Phillips PPJ, et al. A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis. Nature Medicine. Published online 5 November 2018. DOI:10.1038/s41591-018-0224-2

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