A new four-month treatment course for drug-sensitive tuberculosis (the most common form of TB) is as safe and effective as the current six-month treatment course that has been in use since the 1980s, according to findings from an extensive study.
Experts say the findings “mark the biggest shift in TB care in decades”.
The development is expected to translate to cost-savings for funders and better experiences for patients, who often struggle to take medication for half a year. This is according to Dr Susan Dorman, a TB expert based at the Medical University of South Carolina, who presented the results at a press conference on Wednesday, 21 October for the 51st Union World Conference on Lung Health taking place virtually this week.
The trial (Study 31/A5349) was led by the United States Centers for Disease Control and Prevention’ (CDC) Tuberculosis Trials Consortium (TBTC), with collaboration from another US body, the Aids Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
Rifapentine and moxifloxacin
The trial was divided into three: the current six-month standard of care, a four-month treatment course that replaces two drugs in the standard regimen with rifapentine and moxifloxacin, and a four-month arm, swapping rifapentine into the standard of care combination.
While the last of these combinations was inferior to the standard of care, the rifapentine-moxifloxacin combination was found to be non-inferior to the standard of care on a range of measures of safety and efficacy. The study used a non-inferiority margin of 6.6%. The term “non-inferior” is a technical term that essentially means “as good”.
According to Dorman, almost 90% of people receiving the standard of care were successfully treated compared to 88% in the rifapentine-moxifloxacin group. Though the latter is lower, it falls within the pre-defined non-inferiority margin and is thus considered being close enough for the rifapentine-moxifloxacin combination to be considered as good as the standard of care.
The study included 2,500 people with TB at 34 sites in 13 countries, making it the largest TB treatment trial in decades. It also included diverse populations affected by TB such as people living with HIV, HIV-positive people with severely weakened immune systems, people with more serious forms of TB disease and adolescents.
The findings have not yet been published in a medical journal.
TB co-director at the New York-based advocacy organisation Treatment Action Group (TAG), Mike Frick, told Spotlight that these results mark “the biggest jump or shift in TB care in decades”.
“It kind of changes everything,” he said.
There are expected to be some cost-savings attached to a two-month cut in treatment length, but there is uncertainty on whether or not the amount of money spent on the actual drugs will come down, said Dorman, who also represents both bodies involved in the trial (the TBTC and NIAID/NIH). While the current six-month treatment is dirt-cheap, rifapentine and moxifloxacin are both comparatively expensive – although this may change over time.
“[The] important question about cost really includes two [main] ideas. Firstly, the cost of new medicines, for example rifapentine and moxifloxacin, as well as their supply,” said Dorman.
She added that the “other part of the cost equation is how much can be saved in reducing the length of treatment” including funds “potentially saved by TB programmes and at the TB-provider level and time cost saved by participants on their own work and economic activities”.
Easier to complete treatment
According to a CDC press release, shortened treatment “can benefit patients, families, healthcare providers and health systems” and “can help patients more easily complete treatment for TB disease than they would on the existing standard regimen”.
“This is especially important in the era of Covid-19, which has caused widespread disruptions to care and treatment access for many people with TB disease. The availability of shorter regimens enables patients to be cured faster, and has the potential to reduce treatment costs, improve patient quality of life, increase completion of therapy, and reduce development of drug resistance,” it noted.
Drug-resistance develops when patients stop taking their treatment before the course is complete or who do not take their drugs as prescribed. Drug-resistant TB is more difficult – and takes longer – to treat, with a much worse prognosis.
“We receive the results with a lot of gratification and happiness. TB-affected communities have always wished for shorter, easier TB treatment with fewer side effects. We strongly believe this is a real breakthrough, as the new regimen will generate better treatment outcomes for TB patients. We are on the path to wipe out TB as a killer disease,” said TAG’s Dorothy Namutamba in the release.
“We call for national TB programmes, regulatory agencies, and international organisations to make this four-month regimen of existing drugs available as soon as possible – starting in the countries that hosted clinical trials sites that made this result possible,” said Frick.
“Considering that this was a publicly funded study, the results should be considered as a public good made available to all. We further encourage funders and researchers to fill remaining data gaps so that this new, shorter regimen can be used in children under 12, in pregnant women, and in people with comorbidities not included in Study 31/A5349,” he said.
Frick explained that, even if the drugs ended up being affordable to low-and middle-income countries, there remain a number of bureaucratic processes to take place before the new regimen can actually get to patients.
“Following the presentation of the results, an application will be submitted to the World Health Organisation to evaluate the results to be considered to be included in its updated TB treatment guidelines. After this, governments will have to update national guidelines in response to that,” he said.
But many, including Dr Arne von Delft from South African advocacy organisation TB Proof, are still hopeful TB treatment can be shortened even further in future.
He told Spotlight that “four months is still a long time” and that moxifloxacin in particular “is far from safe”.
“But this is promising progress nevertheless,” he said. DM