In a breakthrough for patients with multi-drug-resistant (MDR) tuberculosis (TB), researchers shared positive trial results for a shorter, tailored alternative at the World Conference on Lung Health in Bali, Indonesia. 

The insights came from the endTB-Q trial aimed at finding a simpler, less toxic, shorter regimen for fluoroquinolone-resistant MDR-TB. Fluoroquinolone is a common class of medicine used to treat MDR TB, and if patients become resistant, they are considered to be bordering on extensively drug-resistant (XDR) TB, which is extremely hard to treat and can take 18 months.

The endTB-Q clinical trial enrolled 323 patients from India, Kazakhstan, Lesotho, Pakistan, Peru, and Vietnam to try to find alternatives to the current longer treatment regimen recommended by the World Health Organization (WHO). 

“Our trial innovated in several important ways. Since we know that treatment for TB is not ‘one size fits all’, we tested a strategy that tailored treatment duration to disease severity and treatment response based on simple criteria,” said Lorenzo Guglielmetti, Médecins Sans Frontières (MSF) Director for the endTB project and co-principal investigator of the trial.  

Researchers tried a combination of four TB drugs used to treat drug-resistant forms of TB –  bedaquiline, clofazimine, delamanid and linezolid (BCDL). 

These drugs were given for six months and extended to nine months in case of delayed treatment response. Around 87% of patients were cured after the treatment in comparison to  89% of patients in the control arm of the trial that received the current WHO regime.

But those 87% who did get better had less severe TB, according to the researchers. But for people with severe TB disease, BCDL for nine months was insufficient as they were at risk of TB returning and the longer regimen is still the best option.

“Our conclusions are that this regimen, BCDL, given for six to nine months, is an excellent approach for those who don’t have severe disease at baseline.  In this group, the success rate is almost 95% and it has a big advantage compared to the historical conventional treatment because it’s much shorter and less toxic,” said Guglielmetti.

Bedaquiline use in children found safe

Researchers also shared updates from a separate trial that looked into whether children can take bedaquiline, which is used to treat drug-resistant TB. The trial found the drug to have a high degree of safety and tolerance for use in children. 

New data from a different trial funded by the US-research agency National Institute of Health (NIH) called IMPAACT that included experts from Stellenbosch University in South Africa found bedaquiline safe for use in the treatment of infants, children and adolescents with drug-resistant TB. 

This is a crucial finding as it will allow further optimising the use of bedaquiline in children with drug-resistant TB – an under-served population.

“The P1108 trial [bedaquiline] has paved the way for access, finally, to effective, shorter and safer treatment for children with drug-resistant TB. For too long children with TB have been left behind,” said researcher Simon Schaaf. 

He said that children form nearly 12% of all TB cases or 1.3 million cases every year globally but despite bedaquiline being authorized for use since 2012, there wasn’t any trial for its use in children.

Nearly 3,900 stakeholders including industry representatives, patient groups, and doctors from around 150 countries attended the conference.

The week-long conference also saw the release of results from other TB trials in countries across Southeast Asia. 

In Indonesia, researchers found that using mobile chest X-ray screening proved to be a useful tool to find active TB cases in the community. This is especially helpful in cases where people do not show classic symptoms of TB like coughing.

Day 2 at #UnionConf24 is underway!

👉 @FIT_eV present their research into active case finding among communities in Vietnam🇻🇳

“Community chest X-ray screening for TB among ethnic minority communities is more than just a health intervention—it’s a vital step toward equity”#EndTB pic.twitter.com/Hn0iAzpr1V

— The Union (@TheUnion_TBLH) November 13, 2024

In Vietnam, researchers stressed the importance of active case finding in ethnic minorities and remote communities to ensure access to treatment. They also used mobile X-ray machines.  

In the Philippines, person-centred active case finding for TB was found to break down barriers to healthcare access for vulnerable populations. The screening was done as a part of a poverty alleviation programme which empowered community members to participate and take a leading role. Trust in community leaders aided the screening of TB. 

Researchers also shared results from a study that highlighted the need to optimize tests to check whether a patient was susceptible to a particular drug or not, and to expand access to new TB compounds for people with life-threatening TB.

“Antimicrobial resistance is among the greatest global health threats we face today. For people at-risk of TB, this threat is multiplied,” said Dr Cassandra Kelly-Cirino, Executive Director of The International Union Against Tuberculosis and Lung Disease (The Union), which convened the conference.

“The new research presented at the Union Conference this week represents an invaluable step in managing this challenge and in offering hope to patients of all ages living with extensively drug-resistant TB.”

Image Credits: The Union, The Union.