On 29 January 2025, the New England Journal of Medicine (NEJM) published the manuscript of the endTB clinical trial results. This multi-year study led by a group of non-governmental organizations found shorter, all-oral and more tolerable treatment options for people living with some of the most difficult-to-treat forms of tuberculosis (TB): multidrug/rifampicin-resistant TB (MDR/RR-TB). The publication in the NEJM, a leading peer-reviewed medical journal that publishes cutting-edge research advancing global healthcare, reinforces the strong scientific value of the evidence produced by endTB.
In this interview, Dr. Lorenzo Guglielmetti, MSF Co-Principal investigator for the endTB clinical trial, describes how the trial findings and their publication in a scientific journal could benefit hundreds of thousands of people living with TB worldwide, while the fight against the killer disease is still far from over.
Full manuscript here: “Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis”
NEJM “quick take” video here (you must be signed in/create an NEJM account to do so).
The endTB trial results have been groundbreaking for the treatment of drug-resistant tuberculosis. What do these results mean?
Lorenzo Guglielmetti: The endTB trial results are a milestone in the fight against MDR/RR-TB, a form of tuberculosis that is very difficult to treat because it became resistant to standard medication. In the trial, we saw remarkable cure rates with three new TB regimens – combinations of TB drugs that had not been used as such before. They all are 9-month treatment regimens and include four to five drugs. These regimens significantly reduce the treatment duration compared to the 18-month standard treatment. They have a similar or increased efficacy. For patients, these results are crucial. Traditional MDR/RR-TB treatment is often a long and difficult battle with considerable side effects. The new regimens tested in the endTB trial can drastically improve the patients’ quality of life. They make it easier for patients to complete the full treatment and ultimately increase the chances of full recovery. The endTB trial results complement other recent research breakthroughs. For the first time in decades, we’re seeing real, sustainable progress in treating this form of TB.
Why was the endTB clinical trial launched eight years ago?
Lorenzo Guglielmetti: The endTB trial is part of a larger project, led by a group of non-governmental organizations, which aimed to increase the knowledge on the efficacy and safety of two new drugs for MDR/RR-TB, bedaquiline and delamanid. These new drugs were the first new TB drugs developed in almost 50 years –a great promise for the fight against TB- but pharmaceutical companies did not see the value in completing their development by creating treatment regimens for a disease that predominately affects poorer communities.
The endTB trial data provides much-needed evidence on the optimal combination of these new drugs with older ones. Moreover, the endTB trial was specifically designed to identify multiple treatment options which may suit patients affected by different forms of MDR/RR-TB or with different drug intolerances or other contraindications. In TB treatment, like in other fields of medicine, it is time to move beyond the usual paradigm of a strict “one size fits all” approach.
What does the publication of the endTB results by the New England Journal of Medicine represent?
Lorenzo Guglielmetti: When study results are published, such as the endTB trial results, they become part of the open-access scientific literature, contributing to the ongoing advancement of medical knowledge. This helps guide future research, improves our understanding of diseases and treatments, and allows other scientists to build on the findings. This publication in the NEJM will help medical practitioners and people affected by MDR/RR-TB in the process of sharing decision-making among the different treatment options. Publishing full results in widely accessible medical journals ensures that the information reaches a global audience, including researchers in settings with high incidence of TB, who may particularly benefit from new interventions or approaches.
Millions of people are currently affected by multidrug-resistant tuberculosis worldwide, with thousands dying every year. Looking ahead and building on the endTB trial results, what are the next steps to achieve better cure rates in the coming years?
Lorenzo Guglielmetti: This publication in the NEJM is adding to the World Health Organization (WHO) Rapid Communication which recommended three endTB regimens for MDR/RR-TB treatment in 2024, which was a considerable breakthrough. The next steps remain critical in ensuring these results are implemented on a global scale. We need to work on scaling up access to these new regimens, particularly in countries with high burden of MDR/RR-TB. Access both to rapid diagnostic tests -which are needed to identify patients who will benefit the most from these treatments- and to TB drugs included in the recommended regimens has to be provided to all MDR/RR-TB patients globally. Continued investment in TB research is necessary to stay ahead of emerging resistance and to push the boundaries of what we know about the disease.
Where can the endTB trial data be found?
Lorenzo Guglielmetti: In fact, the endTB data is now available for independent researchers! The endTB Data Sharing Initiative aims to give ethical, equitable and transparent access to endTB data for a range of users who share the common goal of increasing information to improve care for MDR-TB patients. It includes data from the endTB Observational study (more than 2700 study participants), the endTB clinical trial (more than 700 participants) and will include the endTB-Q trial data (more than 300 participants) as well. This is targeted to researchers, research institutions, PhD students, and other users who are interested in analyzing a high-quality dataset on MDR/RR-TB – with the ultimate goal of improving MDR/RR-TB care. More information on eDSI, including on how to submit a Data Access Request, is available on endTB.org.
>> Read the article from the Harvard Medical School
