Shorter, better treatments for multidrug-resistant tuberculosis

Determining the best treatment regimens for patients with MDR-TB

Challenges

According to the 2022 Global Tuberculosis Report, globally, the estimated number of people who developed MDR-TB or RR-TB (MDR/RR-TB) each year was relatively stable between 2015 and 2020, but it grew in 2021. There were an estimated 450,000 incident cases in 2021, up 3.1% from 437,000 in 2020. The main explanation for the increase is the overall increase in TB incidence between 2020 and 2021, which is estimated to have been caused by the impact of the COVID-19 pandemic on TB detection.

Worldwide, only 57% of MDR-TB patients are currently successfully treated. In accordance with WHO guidelines, detection of MDR/ RR-TB requires bacteriological confirmation of TB and testing for drug resistance using rapid molecular tests, culture methods or sequencing technologies.

Treatment requires a course of second-line drugs for at least nine months and up to twenty months, supported by counselling and monitoring for adverse events. WHO recommends expanded access to all-oral regimens. Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat.

Solutions

endTB is a 8-year project that has aimed to contribute to reducing morbidity and mortality from MDR- TB through delivering clinical evidence on safety and efficacy of scalable, effective treatment regimens that are less toxic, shorter, and less expensive than the existing standard of care. The project has sought to meet this goal through increased access to new and repurposed drugs for MDR-TB and through scientific research on scalable regimens.

The project’s key outputs have been (1) an observational study of the new MDR-TB drugs use in eligible patients in 17 countries that examined the safety and efficacy of bedaquiline (BDQ) and delamanid (DLM) as part of multi-drug regimens for treatment of MDR-TB in routine conditions (activities related to this study ended in 2019), and (2) two clinical trials to identify less toxic and more effective ways to treat MDR-TB patients (with and without fluoroquinolone resistance) using the new drugs.

Progress so far

Through translation of evidence from the operational research into WHO guidance, endTB has generated demand and accelerated acceptance for new TB regimens.

The endTB project observational study completed enrollment of nearly 3,000 participants in 2018, across the original 17 endTB countries. The data from the study helped shape national guidelines supporting the use of new TB drugs on a global level, informing the 2022 revision of the global MDR-TB treatment guidelines.

The endTB clinical trial completed follow-up of patients in 2023. So far there are encouraging indicators of the trial success with 80% of participants that had a favourable validated, primary outcome.

By April 2023, the endTB–Q has completed enrolment. Results from the Q trial are expected in 2024.

As the project approaches closure and transition, the main priorities for 2023 are: delivering results for all endTB regimens; depending on the results, advocating for guideline revision, and completing data sharing with WHO.

In late 2022, WHO recommended use of new regimen BPal/M, this new regimen offers better outcomes and considerably shortens the duration of treatment, however the regimen excludes key populations such as children, adolescents, pregnant and breastfeeding women, and people with bedaquiline resistance and allergies. To address these subgroups, further support is needed for evidence to support WHO guidelines that would provide alternatives to BPaL/M such as delamanid-containing or linezolid-sparing regimens. The results of endTB will inform these evidence gaps for the excluded subgroups. Notably, the cost of the component drugs on both BPaL/M and endTB regimen are currently prohibitive.

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