University of Cape Town: Study shows the benefits of a novel, short and all-oral treatment for multidrug-resistant TB

A recently published study by academics from the University of Cape Town (UCT) has signaled a paradigm shift in the treatment of multidrug-resistant tuberculosis (MDR-TB), which could encourage more people to complete their medication and be cured from this dreaded disease.

The NExT study has shown that a shorter six-month regimen of a combination of drugs which could be taken orally was twice as likely to lead to favourable outcomes than the traditional approach, which included four to six months of injections.

This is seen as an important step in the battle against MDR-TB, a virulent form of TB caused by bacteria that do not respond to the two most powerful, first-line anti-TB drugs – isoniazid and rifampicin.

“There are huge benefits to a shorter treatment time, while the cost of the treatment could be dramatically reduced,” said pulmonologist and specialist physician, Dr Ali Esmail, who heads the clinical trial unit at the UCT Lung Institute and was the study lead for the NExT trial.

“Shorter treatment time and an all-oral regimen means people will be able to get back to work and daily life. They can also take the treatment at home instead of coming into the clinic almost every day for injections. This also relieves the burden on the healthcare system. A shorter treatment regimen could also go far in retaining patients so that they can complete their treatment course,” said Dr Esmail.

Research across four provinces

This was the first published randomised control trial to evaluate the efficacy of an all-oral six-month regimen for MDR-TB. It was carried out in sites in Cape Town, Gqeberha, George, Durban and Klerskdorp. Participants were randomly assigned to receive the novel six-month oral treatment regimen compared to the World Health Organization (WHO)-approved injectable-based regimen.

The study was funded by the South African Medical Research Council (SAMRC).

SAMRC president and CEO, Professor Glenda Gray, has described the findings as a huge advance in TB control in South Africa and beyond. “Not only do the findings have the potential to change TB clinical practice but could also transform the way we treat patients with drug-resistant forms of TB here at home and in other parts of the world.”

An important milestone

The NExT study has been described as setting a new benchmark for the treatment of MDR-TB by Professor Keertan Dheda, the principal investigator of the study from UCT and the London School of Hygiene and Tropical Medicine.

The findings of the study were published in the American Journal of Respiratory and Critical Care Medicine in February 2022.

The study has also attracted the interest of the WHO, which requested the data and has set up a working group that is looking into the question of shortening the treatment duration.

Most MDR-TB patients cannot access newer drugs and the injectable regimen unfortunately remains the standard of care in many TB-endemic countries.

Replacing painful injections

Esmail described his experience of how patients, some of whom were very emaciated and sick with advanced HIV, had dreaded having the injections. “Injections are supposed to be given in the muscle. Sometimes you have to inject into a sliver of muscle right on the bone. It can be incredibly painful. Additionally, injectable agents can cause permanent hearing loss leading to disability in this highly vulnerable group of patients.”

“We also need to think about delivering antibiotics for TB in a different way and to get them directly into the cavities.”

As a result, some people decide not to complete their treatment. This in turn has detrimental effects for the patient, but also increases the risk of spreading MDR-TB in the community.

According to the WHO, 500 000 people every year fall ill with MDR-TB globally. South Africa carries a high burden of MDR-TB.

Drug-resistance emerges when anti-TB medicines are used inappropriately, through incorrect prescription by healthcare providers, poor quality drugs and when patients stop treatment prematurely.

MDR-TB as a global emergency

“Resistance can develop very quickly and developing new drugs is time consuming and extremely expensive. We have to think about this as a global emergency and do all we can to stop it,” said Esmail.

While MDR-TB is treatable and curable using second-line drugs, treatment options are limited, and medicines are both expensive and toxic. Esmail said many challenges remain in the treatment of MDR-TB, and designing a more efficacious, all-oral regimen using newer drugs could be a natural follow-up to the NExT study.

“The burden of lung damage induced by TB also needs to be addressed as patients recovering from TB are left with a disability.”

“We also need to think about delivering antibiotics for TB in a different way and to get them directly into the cavities. Inhaled antibiotics, such as those we use for cystic fibrosis, go straight into the lungs and is therefore a promising idea for TB. It’s a field that needs to be advanced. Finally, the burden of lung damage induced by TB also needs to be addressed as patients recovering from TB are left with a disability. Very little research is available in this area and needs to be remedied.”

Esmail said he was concerned about the impact COVID-19 has had on TB and that transmission rates could rise further without concerted action.

“We have to catch up with the gains we had made before COVID-19. Clinicians, policymakers, health facilities, researchers and advocates have to come on board to ensure that we get back on track in diagnosing and treating TB as soon as possible. We have to work extra hard to achieve this.”

Dr Norbert Ndjeka, the director for Drug-Resistant TB, TB & HIV at the National Department of Health, said high loss to follow up and high death rates were South Africa’s major challenges in managing MDR-TB.

“We are very excited about the NeXT study results as a shorter treatment regimen could go a long way in reducing loss to follow-up.”

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