The latest evidence-based guidance for the treatment of drug-resistant TB was published by WHO in December 2018. Since these guidelines were released, new evidence relevant to drug-resistant TB treatment has become available prompting WHO to initiate a new guideline update process. The scope of the upcoming guidelines update is driven by the need to ensure rapid access to better treatment options for people with drug-resistant TB and is expected to be addressed by review of the new data pledged by member states and technical partners of WHO. A Guideline Development Group (GDG) meeting will be convened for this purpose from 12 to 14 November 2019.
“The upcoming update of guidelines on drug-resistant TB treatment is an important step to accelerate global and country efforts to tackle drug-resistant TB,” said Dr Tereza Kasaeva, Director of the WHO Global TB Programme. “This is critical to save lives and ensure better outcomes for the hundreds of thousands of people struggling with drug-resistant TB."
Four main questions will guide the review and analysis of evidence at the GDG meeting:
Question 1. In MDR/RR-TB patients, does an all-oral treatment regimen lasting 9-12 months and including bedaquiline, safely improve outcomes when compared with other regimens conforming to WHO guidelines?
Question 2. In XDR-TB patients or patients who are treatment intolerant or with non-responsive MDR-TB, does a treatment regimen lasting 6-9 months composed of bedaquiline, pretomanid and linezolid safely improve outcomes when compared with other regimens conforming to WHO guidelines?
Question 3. In MDR/RR-TB patients, does a treatment regimen containing bedaquiline for more than six months safely improve outcomes when compared with bedaquiline for up to six months as part of longer regimens otherwise conforming to WHO guidelines?
Question 4. In MDR/RR-TB patients, does concurrent use of bedaquiline and delamanid safely improve outcomes when compared with other treatment regimen options otherwise conforming to WHO guidelines?
WHO Global TB Programme (GTB) has actively collaborated with national programmes and technical partners to ensure new evidence was made available for the guidelines update in a timely manner: Programmatic data of MDR/RR-TB patients from South Africa treated with all-oral bedaquiline containing shorter regimens (i.e.< 12-months duration) where the injectable was replaced by bedaquiline. The dataset, provided by the Department of Health of South Africa, includes approximately 4000 individuals treated in 2017 with the all-oral bedaquiline containing shorter regimen and in whom the final treatment outcomes as well as follow up data were available. This dataset precedes the change in the treatment regimen for all patients with drug-resistant TB announced by South Africa in 2018.
The datasets from a study of a novel all oral-regimen consisting of bedaquiline, pretomanid and linezolid (BPaL) for 6-9 months – the Nix-TB Trial. The dataset, made available by TB Alliance, includes about 100 records of XDR-TB patients and MDR-TB patients who were treatment intolerant or non-responsive to treatment.
A dataset of MDR/RR-TB and XDR-TB patients treated with bedaquiline and/or delamanid containing regimens from the observational study of the endTB project financed by Unitaid and implemented by three organizations – Partners in Health (PIH), Médecins Sans Frontières (MSF) and Interactive Research and Development (IRD). The data set includes approximately 1,000 records of patients treated with various longer regimens including new and repurposed TB medicines. Nearly one third of those individuals were treated with bedaquiline for longer than 6 months and less than 100 patients received regimens with both bedaquiline and delamanid.
In preparation for this update, to ensure completeness of relevant evidence, WHO issued a public call for data on 1 August 2019. The public call requested researchers, national TB programs and technical agencies to provide individual patient data on MDR/RR-TB treatment with the requirements aligned with the focus of the 2019 guidelines update and resulted in:
A dataset provided by MSF with approximately 200 records of patients on MDR/RR-TB treatment using second-line TB drugs recommended in the WHO guidelines from India and Uzbekistan, and a dataset with about 100 records provided by the National TB Programme of the Republic of Belarus.
In addition, preliminary results from the cohort study of approximately 100 women, with a number of them treated for MDR/RR-TB using bedaquiline-containing regimens during pregnancy between 2013 and 2017 in KwaZulu-Natal, South Africa will be shared during GDG meeting.
The GDG convened by WHO Global TB Programme for this meeting and review of available evidence is a gender balanced and multidisciplinary group composed of external experts selected to encompass the relevant expertise, technical skills, diverse perspectives and includes individuals from all WHO regions and countries with the high burden of drug-resistant TB, technical experts, end-users of the guidelines, TB and MDR-TB survivors and affected communities, groups affected by the recommendations, experts in assessing evidence and civil society taskforce representatives.
In advance of the GDG meeting, several consultations were held with civil society representatives and partners through webinars and calls on the MDR-TB guideline development process, by the WHO Global TB Programme, the Office of the WHO Chief Scientist and other departments.
The Global TB Programme thanks National TB Programmes and technical partners for sharing new evidence and their response to the public call for data.
“The upcoming update of guidelines on drug-resistant TB treatment is an important step to accelerate global and country efforts to tackle drug-resistant TB,” said Dr Tereza Kasaeva, Director of the WHO Global TB Programme. “This is critical to save lives and ensure better outcomes for the hundreds of thousands of people struggling with drug-resistant TB."
Four main questions will guide the review and analysis of evidence at the GDG meeting:
Question 1. In MDR/RR-TB patients, does an all-oral treatment regimen lasting 9-12 months and including bedaquiline, safely improve outcomes when compared with other regimens conforming to WHO guidelines?
Question 2. In XDR-TB patients or patients who are treatment intolerant or with non-responsive MDR-TB, does a treatment regimen lasting 6-9 months composed of bedaquiline, pretomanid and linezolid safely improve outcomes when compared with other regimens conforming to WHO guidelines?
Question 3. In MDR/RR-TB patients, does a treatment regimen containing bedaquiline for more than six months safely improve outcomes when compared with bedaquiline for up to six months as part of longer regimens otherwise conforming to WHO guidelines?
Question 4. In MDR/RR-TB patients, does concurrent use of bedaquiline and delamanid safely improve outcomes when compared with other treatment regimen options otherwise conforming to WHO guidelines?
WHO Global TB Programme (GTB) has actively collaborated with national programmes and technical partners to ensure new evidence was made available for the guidelines update in a timely manner: Programmatic data of MDR/RR-TB patients from South Africa treated with all-oral bedaquiline containing shorter regimens (i.e.< 12-months duration) where the injectable was replaced by bedaquiline. The dataset, provided by the Department of Health of South Africa, includes approximately 4000 individuals treated in 2017 with the all-oral bedaquiline containing shorter regimen and in whom the final treatment outcomes as well as follow up data were available. This dataset precedes the change in the treatment regimen for all patients with drug-resistant TB announced by South Africa in 2018.
The datasets from a study of a novel all oral-regimen consisting of bedaquiline, pretomanid and linezolid (BPaL) for 6-9 months – the Nix-TB Trial. The dataset, made available by TB Alliance, includes about 100 records of XDR-TB patients and MDR-TB patients who were treatment intolerant or non-responsive to treatment.
A dataset of MDR/RR-TB and XDR-TB patients treated with bedaquiline and/or delamanid containing regimens from the observational study of the endTB project financed by Unitaid and implemented by three organizations – Partners in Health (PIH), Médecins Sans Frontières (MSF) and Interactive Research and Development (IRD). The data set includes approximately 1,000 records of patients treated with various longer regimens including new and repurposed TB medicines. Nearly one third of those individuals were treated with bedaquiline for longer than 6 months and less than 100 patients received regimens with both bedaquiline and delamanid.
In preparation for this update, to ensure completeness of relevant evidence, WHO issued a public call for data on 1 August 2019. The public call requested researchers, national TB programs and technical agencies to provide individual patient data on MDR/RR-TB treatment with the requirements aligned with the focus of the 2019 guidelines update and resulted in:
A dataset provided by MSF with approximately 200 records of patients on MDR/RR-TB treatment using second-line TB drugs recommended in the WHO guidelines from India and Uzbekistan, and a dataset with about 100 records provided by the National TB Programme of the Republic of Belarus.
In addition, preliminary results from the cohort study of approximately 100 women, with a number of them treated for MDR/RR-TB using bedaquiline-containing regimens during pregnancy between 2013 and 2017 in KwaZulu-Natal, South Africa will be shared during GDG meeting.
The GDG convened by WHO Global TB Programme for this meeting and review of available evidence is a gender balanced and multidisciplinary group composed of external experts selected to encompass the relevant expertise, technical skills, diverse perspectives and includes individuals from all WHO regions and countries with the high burden of drug-resistant TB, technical experts, end-users of the guidelines, TB and MDR-TB survivors and affected communities, groups affected by the recommendations, experts in assessing evidence and civil society taskforce representatives.
In advance of the GDG meeting, several consultations were held with civil society representatives and partners through webinars and calls on the MDR-TB guideline development process, by the WHO Global TB Programme, the Office of the WHO Chief Scientist and other departments.
The Global TB Programme thanks National TB Programmes and technical partners for sharing new evidence and their response to the public call for data.