Treatment of drug-resistant tuberculosis with bedaquiline in a high HIV prevalence setting: an interim cohort analysis

Ndjeka, Norbert; Conradie, Francesca; Schnippel, Kathryn; Hughes, Jennifer; Bantubani, Nonkqubela; Ferreira, Héverson Batista; Maartens, Gary; Mametja, David; Meintjes, Graeme; Padanilam, Xavier; Variava, Ebrahim; Pym, Alexander S.; Pillay, Yogan

doi:10.5588/ijtld.14.0944

Cited by 127 publications

(113 citation statements)

References 11 publications

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“…Further, newly published results of the C209 trial [43] as well as recent published interim data from the ongoing Compassionate Use program for bedaquiline in France, South Africa, and Latvia [40][41][42]44], suggest a lower mortality rate than that observed in the C208 trial, justifying this assumption.…”

Section: Discussionmentioning

confidence: 84%

“…Briefly, the use of trial data for bedaquiline and delamanid may not accurately reflect results found in German clinical practice. However, the results were not found to differ substantially when interim data from real-world evidence studies from a European and African setting were applied in sensitivity analyses [40][41][42], and therefore, the results of this analysis can be assumed to be applicable in the realworld setting.…”

Section: Discussionmentioning

confidence: 99%

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Cost-Effectiveness of Adding Novel or Group 5 Interventions To A Background Regimen For The Treatment of Multidrug-Resistant Tuberculosis In Germany

2016

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Background: Treatment of multidrug-resistant tuberculosis (MDR-TB) is complex, lengthy, and involves a minimum of four drugs termed a background regimen (BR), that have not previously been prescribed or that have proven susceptible to patient sputum culture isolates. In recent years, promising new treatment options have emerged as add-on therapies to a BR. The aim of this study was to evaluate the long-term costs and effectiveness of adding the novel or group 5 interventions bedaquiline, delamanid, and linezolid to a background regimen (BR) of drugs for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (MDR-TB), within their marketing authorisations, from a German healthcare cost-effectiveness perspective. Methods: A cohort-based Markov model was developed to simulate the incremental cost-effectiveness ratio of bedaquiline plus BR, delamanid plus BR, or linezolid plus BR versus BR alone in the treatment of MDR-TB, over a 10-year time horizon. Effectiveness of treatment was evaluated in Quality-Adjusted Life-Years (QALYs) and LifeYears Gained (LYG), using inputs from clinical trials for bedaquiline and delamanid and from a German observational study for linezolid. Cost data were obtained from German Drug Directory costs (€/2015), published literature, and expert opinion. A 3% yearly discount rate was applied. Probabilistic and deterministic sensitivity analyses were conducted. Results: The total discounted costs per-patient were €85,575 for bedaquiline plus BR, €81,079 for delamanid plus BR, and €80,460 for linezolid plus BR, compared with a cost of €60,962 for BR alone. The total discounted QALYs per-patient were 5.95 for bedaquiline plus BR, 5.36 for delamanid plus BR, and 3.91 for linezolid plus BR, compared with 3.68 for BR alone. All interventions were therefore associated with higher QALYs and higher costs than BR alone, with incremental costs per QALY gained of €22,238 for bedaquiline, €38,703 for delamanid, and €87,484 for linezolid, versus BR alone. In a fully incremental analysis, bedaquiline plus BR was the most cost-effective treatment option at thresholds greater than €22,000 per QALY gained. In probabilistic analyses, the probability that bedaquiline plus BR was the most cost-effective treatment strategy at a willingness-to-pay threshold of €30,000 was 54.5%, compared with 22.9% for BR alone, 18.2% for delamanid plus BR, and 4.4% for linezolid. Conclusions: In Germany, the addition of bedaquiline, delamanid, or linezolid to a BR would result in QALY gains over BR alone. Based on this analysis, bedaquiline is likely to be the most cost-effective intervention for the treatment of MDR-TB, when added to a BR regimen at thresholds greater than €22,000 per QALY.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Cost-Effectiveness of Adding Novel or Group 5 Interventions To A Background Regimen For The Treatment of Multidrug-Resistant Tuberculosis In Germany

2016

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“…Although people with HIV were largely excluded from the phase IIb clinical trials of both bedaquiline and delamanid, some data on the safety and efficacy of bedaquiline have emerged in cohorts in South Africa and Swaziland. 324 Bedaquiline should not be given with efavirenz, however, since efavirenz decreases the serum concentration of bedaquiline. Delamanid does not appear to have significant interactions with any of the antiretroviral mediations (table 7).…”

Section: Management In Special Situationsmentioning

confidence: 99%

“…In postmarketing studies, an increase in mortality was not seen. 324 WHO recommends that bedaquiline be given for 6 months for treatment of MDR tuberculosis in adult patients who don't have other treatment options. 270 Mortality concerns in the phase 2 study and the reduction in bedaquiline concentrations by more than 50% with the concurrent use of rifampicin has prevented its investigation as a first-line treatment-shortening regimen.…”

Section: Bedaquilinementioning

confidence: 99%

“…Although encouraging initial observations have been made of faster culture conversion in early bactericidal activity and phase 2 studies of bedaquiline, 365,366 and high rates of culture conversion in French 367 and South African patients with XDR tuberculosis (100% in the French cohort and 85% in the South African cohort), 324 another analysis 368 indicated that the 120-week culture conversion rate was 70% in patients with pre-XDR tuberculosis and 62% in XDR tuberculosis when bedaquiline was used with companion drugs and an optimised background regimen. Thus, even with newer drugs such as bedaquiline, treatment failure will be common in patients with XDR tuberculosis or those with resistance beyond XDR tuberculosis, for which no effective therapy is available and so it remains programmatically incurable.…”

Section: Bedaquilinementioning

confidence: 99%

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The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Dheda

Gumbo

Maartens

et al. 2017

The Lancet Respiratory Medicine

506

474

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What lies beneath the airway mucosal barrier? Throwing the spotlight on antigen‐presenting cell function in the lower respiratory tract

2020

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The global prevalence of respiratory infectious and inflammatory diseases remains a major public health concern. Prevention and management strategies have not kept pace with the increasing incidence of these diseases. The airway mucosa is the most common portal of entry for infectious and inflammatory agents. Therefore, significant benefits would be derived from a detailed understanding of how immune responses regulate the filigree of the airways. Here, the role of different antigen‐presenting cells (APC) in the lower airways and the mechanisms used by pathogens to modulate APC function during infectious disease is reviewed. Features of APC that are unique to the airways and the influence they have on uptake and presentation of antigen to T cells directly in the airways are discussed. Current information on the crucial role that airway APC play in regulating respiratory infection is summarised. We examine the clinical implications of APC dysregulation in the airways on asthma and tuberculosis, two chronic diseases that are the major cause of illness and death in the developed and developing world. A brief overview of emerging therapies that specifically target APC function in the airways is provided.

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Treatment of drug-resistant tuberculosis with bedaquiline in a high HIV prevalence setting: an interim cohort analysis

Cited by 127 publications

References 11 publications

Cost-Effectiveness of Adding Novel or Group 5 Interventions To A Background Regimen For The Treatment of Multidrug-Resistant Tuberculosis In Germany

Cost-Effectiveness of Adding Novel or Group 5 Interventions To A Background Regimen For The Treatment of Multidrug-Resistant Tuberculosis In Germany

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

What lies beneath the airway mucosal barrier? Throwing the spotlight on antigen‐presenting cell function in the lower respiratory tract

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