Tuberculosis: Documenting the transition to shorter treatments for multidrug-resistant TB under real-life conditions
In recent years, major progress has been made in the fight against tuberculosis (TB), in particular the availability of shorter and more effective treatments for the resistant forms. In the past, people with MDR/RR-TB had to follow a restrictive two-year course of treatment consisting of 20 pills a day and painful daily injections for eight months.
Significant progress has been made in recent years, thanks in particular to clinical trials led by MSF. The first, TB-PRACTECAL showed that the “BPaLM” regimen, a six-month oral treatment combining bedaquiline and pretomanid with the older drugs linezolid and moxifloxacin, had an 89% cure rate. Recognising its many advantages - highly effective, shorter, injection-free, less toxic, with options for everyone - the WHO now recommends BPaLM as first-line treatment for multidrug-resistant tuberculosis in people aged over 14. MSF's endTB trial marked a new milestone. Three new nine-month oral treatments, containing bedaquiline and/or delamanid, demonstrated efficacy at least comparable to standard treatment with improved tolerance in people with multidrug-resistant tuberculosis. The endTB regimens offer treatment options, including for children under the age of 14 and for pregnant and breast-feeding women for whom pretomanid is not recommended.
Towards a patient-centred approach to tuberculosis
Clinicians now have a range of treatments and can choose the best treatment according to medical needs and patient preferences. "Our study aims to document the outcomes of these shorter treatments outside a clinical trial setting, under real-life conditions in Pakistan, with a particular focus on children, pregnant women. In addition, we will study the experiences of patients who require longer treatment due to more severe forms of tuberculosis. These include forms of TB which have additional resistance to the core drugs used in the shorter regimens to treat MDR/RR-TB. For these patients, many uncertainties remain regarding the optimal treatment approach," explains Maria Lightowler, epidemiologist and coordinator of the study.
Pakistan has one of the highest tuberculosis prevalences worldwide and ranks fifth globally in the number of MDR/RR‑TB cases, with an estimated 14,000 cases in 2024, of which just under one third received treatment (1). The study takes place in Punjab province, which accounts for 46% of the country's MDR/XDR-TB cases (2).
In addition, the study aims to describe the efficacy and side-effects of the following different treatments for all people affected including children and pregnant women - under real-life conditions: the new, shorter regimens BPaLM and endTB, as well as older regimens such as the modified Bangladesh nine-month regimen (3), and longer individualised treatment regimens for patients not eligible for the shorter regimens. It will also explore the acceptability and feasibility of these treatment regimens among patients and carers, and their impact on patients' quality of life. Interviews with carers and patients and focus groups with those responsible for the programmatic management of MDR/RR TB will be conducted to gather their impressions. While these new therapeutic regimens open up new prospects in terms of person-centred care, they also change practice and doctor-patient relationships, hence the importance of these qualitative data to better understand these changes as well as adherence to treatment, which is essential to their success.
Encouraging initial results, but vigilance regarding resistance
An initial phase of the study, presented at the World Union Conference on Respiratory Health (November 18-21, 2025)—the largest international meeting dedicated to tuberculosis— revealed excellent results for the BPaLM regimen in real-world conditions. This treatment showed a success rate of 95%. For people who required the other regimens, the results were 74% for the longer individualized 18- to 24-month treatment and 78% for the modified Bangladesh 9-month regimen. The analyses are now continuing, incorporating endTB regimens, which were not yet part of the national recommendations in Pakistan during the first phase of the study.
But beyond effectiveness, the question of emerging drug resistance remains critical.
“Monitoring the development of resistance to the drugs used in these new treatment regimens is also essential," emphasizes Maria Lightowler, epidemiologist in charge of the study. We will describe resistance to anti-tuberculosis drugs, in particular bedaquiline and linezolid, the possible amplification of resistance during treatment and its impact on treatment results."
Moreover, initial results presented to the Union in 2025 show that among patients initially sensitive to bedaquiline, 4 % already showed resistance to this drug.
This study aims to provide a better understanding of the deployment of these new treatments in real-life conditions, which represents a challenge for clinicians and patients faced with several options. Only mixed qualitative and quantitative studies can capture all these aspects, while considering the specific socio-cultural context.
“Bringing these treatments from clinical trials into Pakistan’s real-world health system is the real test. Their success depends not only on the medicines, but on how well they fit into patients’ lives and the everyday work of the clinicians who care for them”, concludes Dr. Abdulwahab Mohamed, MSF medical coordinator in Pakistan.
© Gul Nayab
- Global Tuberculosis Report 2025 https://worldhealthorg.shinyapps.io/tb_profiles/?_inputs_&tab=%22tables%22&lan=%22EN%22&iso3=%22PAK%22&entity_type=%22country%22
- NATIONAL TB CONTROL PROGRAM PAKISTAN. 2019 [cited 2024 Jun 25]; Available from: www.ntp.gov.pk
- Etudiés dans les essais STREAM, ces schémas contiennent de la bédaquiline, de la moxifloxacine, de la clofazimine, du pyrazinamide, de l'éthambutol, de l'éthionamide et de l'isoniazide à forte dose. Une recommandation récente autorise le remplacement de l'éthionamide par le linézolide
