In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy.
Active pharmacovigilance (PV) is recommended for TB programmes, notably for multidrug-resistant TB (MDR-TB) patients treated with new drugs. Launched with the support of UNITAID in April 2015, endTB (Expand New Drug markets for TB) facilitated treatment with bedaquiline (BDQ) and/or delamanid of >2600 patients in 17 countries, and contributed to the creation of a central PV unit (PVU).
Publication: Time for a Change: Considering Regimen Changes in Analyses of Observational MDR/RR-TB Treatment Cohort Data
Randomized clinical trials represent the gold standard in therapeutic research. Nevertheless, observational cohorts of patients treated for multidrug-resistant (MDR) or rifampin-resistant (RR) tuberculosis (TB) also play an important role in generating evidence to guide MDR/RR TB care.
Publication: Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid. A Prospective Multicountry Study
Bedaquiline and delamanid offer the possibility of more effective and less toxic treatment for multidrug-resistant (MDR) tuberculosis (TB). With this treatment, however, some patients remain at high risk for an unfavorable treatment outcome. The endTB Observational Study is the largest multicountry cohort of patients with rifampin-resistant TB or MDR-TB treated in routine care with delamanid- and/or bedaquiline-containing regimens according to World Health Organization guidance.
Publication: Culture Conversion at 6 Months in Patients Receiving Delamanid-containing Regimens for the Treatment of Multidrug-resistant Tuberculosis
Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months.
Publication: The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens
At a time when programs were struggling to design effective regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB), the marketing authorization of bedaquiline and delamanid was a critical development in the MDR-TB treatment landscape. However, despite their availability for routine programmatic use, the uptake of these drugs has remained slow; concerns included a lack of evidence on safety and efficacy and the need to protect the new drugs from the development of acquired resistance. As part of the endTB Project, we aimed to address these barriers by generating evidence on safety and efficacy of bedaquiline or delamanid based MDR-TB regimens.
Purpose: To evaluate the use of Bayesian adaptive randomization for clinical trials of new treatments for multidrug-resistant tuberculosis.
Letter to the editor: High prevalence of hepatitis C infection among multidrug-resistant tuberculosis patients
In “Integrating HCV testing with HIV programs improves hepatitis C outcomes in people who inject drugs: A cluster-randomized trial”, the authors studied an intervention that integrated HCV testing and education into HIV services across India. In our opinion, many national tuberculosis (TB) programs should also consider integrating HCV testing. TB or the highly resistant variant of the disease, multidrug-resistant (MDR) TB, is generally not considered a risk factor for HBV or HCV infection, except in those who are co-infected with HIV or who are intravenous drug users. Routine, systematic testing for HCV is rare in patients with MDR-TB and is not currently recommended in World Health Organization guidelines for MDR-TB treatment.
Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field.
You will find some details about the endTB project in this 2-page infographic.