Estimating post-treatment recurrence after multidrug-resistant tuberculosis treatment among patients with and without HIV: the impact of assumptions about death and missing follow-up

Topics

  • endTB Observational Study

Abstract

Background

Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment follow-up.

Effectiveness of a bedaquiline, linezolid, clofazimine "core" for multidrug-resistant tuberculosis

ABSTRACT

RATIONALE: Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients.

OBJECTIVES: We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline.

Pregnancy and Birth Outcomes in Patients With Multidrug-Resistant Tuberculosis Treated With Regimens That Include New and Repurposed Drugs

Topics

  • endTB Observational Study

ABSTRACT

Among 43 pregnant women receiving multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment with bedaquiline and/or delamanid, 98% had favorable treatment outcomes. Of 31 continued pregnancies, 81% had live births with no reported malformations, and 68% of neonates had normal birth weights. Effective MDR/RR-TB treatment during pregnancy can improve maternal outcomes without harming neonates.

Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis

Topics

  • endTB Observational Study

ABSTRACT

RATIONALE: Current recommendations for the treatment of rifampin- and multidrug-resistant tuberculosis include bedaquiline used for six months or longer. Evidence is needed to inform the optimal duration of bedaquiline.

OBJECTIVES: We emulated a target trial to estimate the effect of three bedaquiline duration treatment strategies (6 months, 7-11 months, ≥ 12 months) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis.

Publication: Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial

Topics

  • endTB-Q Clinical Trial

Background: Treatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens.

Publication: Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs

Background: Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs.

Publication: Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial

Background: Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation.

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

Topics

  • endTB Observational Study

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: Introducing new and repurposed TB drugs: the endTB experience

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.

Publication: Culture conversion at six months in patients receiving bedaquiline- and delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis

Rifampicin-resistant/multidrug-resistant (RR/MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis (TB) are serious public health problem in Kazakhstan. In 2012 and 2013, stringent regulatory authorities approved the first new TB drugs in fifty years, bedaquiline and delamanid, offering hope for more effective and less toxic MDR-TB treatment. The endTB Observational Study is a multi-country study that enrolled patients receiving a bedaquiline- or delamanid-containing regimen for RR/MDR-TB between 01 April 2015 and 30 September 2018.

Publication: The endTB observational study protocol: treatment of MDR-TB with bedaquiline or delamanid containing regimens

Topics

  • endTB Observational Study

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.

Publication: Clinical perspectives on treatment of rifampicin-resistant/ multidrug-resistant TB

Topics

  • Other

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.

Publication: Setting up pharmacovigilance based on available endTB Project data for bedaquiline

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: All-oral longer regimens are effective for the management of multidrug resistant tuberculosis in high burden settings

Recent World Health Organization guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline and/or delamanid as part of their multidrug regimen.
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