Dataset Information

Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

ABSTRACT:

Objective

To evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for multidrug-resistant tuberculosis (MDR-TB) in the United Kingdom (UK).

Methods

A cohort-based Markov model was developed to estimate the incremental cost-effectiveness ratio of bedaquiline plus BR (BBR) versus BR alone (BR) in the treatment of MDR-TB, over a 10-year time horizon. A National Health Service (NHS) and personal social services perspective was considered. Cost-effectiveness was evaluated in terms of Quality-Adjusted Life Years (QALYs) and Disability-Adjusted Life Years (DALYs). Data were sourced from a phase II, placebo-controlled trial, NHS reference costs, and the literature; the US list price of bedaquiline was used and converted to pounds (£18,800). Costs and effectiveness were discounted at a rate of 3.5% per annum. Probabilistic and deterministic sensitivity analysis was conducted.

Results

The total discounted cost per patient (pp) on BBR was £106,487, compared with £117,922 for BR. The total discounted QALYs pp were 5.16 for BBR and 4.01 for BR. The addition of bedaquiline to a BR resulted in a cost-saving of £11,434 and an additional 1.14 QALYs pp over a 10-year period, and is therefore considered to be the dominant (less costly and more effective) strategy over BR. BBR remained dominant in the majority of sensitivity analyses, with a 81% probability of being dominant versus BR in the probabilistic analysis.

Conclusions

In the UK, bedaquiline is likely to be cost-effective and cost-saving, compared with the current MDR-TB standard of care under a range of scenarios. Cost-savings over a 10-year period were realized from reductions in length of hospitalization, which offset the bedaquiline drug costs. The cost-benefit conclusions held after several sensitivity analyses, thus validating assumptions made, and suggesting that the results would hold even if the actual price of bedaquiline in the UK were higher than in the US.

SUBMITTER: Wolfson LJ

PROVIDER: S-EPMC4368676 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

Wolfson Lara J LJ Walker Anna A Hettle Robert R Lu Xiaoyan X Kambili Chrispin C Murungi Andrew A Knerer Gerhart G

PloS one 20150320 3

<h4>Objective</h4>To evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for multidrug-resistant tuberculosis (MDR-TB) in the United Kingdom (UK).<h4>Methods</h4>A cohort-based Markov model was developed to estimate the incremental cost-effectiveness ratio of bedaquiline plus BR (BBR) versus BR alone (BR) in the treatment of MDR-TB, over a 10-year time horizon. A National Health Service (NHS) and personal social services perspective was considered. Cost-ef ...[more]

PMID: 25794045

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Project description:BackgroundThe bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear.MethodsWe enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.e., resistant to rifampin, a fluoroquinolone, and an aminoglycoside), pre-XDR tuberculosis (i.e., resistant to rifampin and to either a fluoroquinolone or an aminoglycoside), or rifampin-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. We randomly assigned the participants to receive bedaquiline for 26 weeks (200 mg daily for 8 weeks, then 100 mg daily for 18 weeks), pretomanid (200 mg daily for 26 weeks), and daily linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks. The primary end point in the modified intention-to-treat population was the incidence of an unfavorable outcome, defined as treatment failure or disease relapse (clinical or bacteriologic) at 26 weeks after completion of treatment. Safety was also evaluated.ResultsA total of 181 participants were enrolled, 88% of whom had XDR or pre-XDR tuberculosis. Among participants who received bedaquiline-pretomanid-linezolid with linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks, 93%, 89%, 91%, and 84%, respectively, had a favorable outcome; peripheral neuropathy occurred in 38%, 24%, 24%, and 13%, respectively; myelosuppression occurred in 22%, 15%, 2%, and 7%, respectively; and the linezolid dose was modified (i.e., interrupted, reduced, or discontinued) in 51%, 30%, 13%, and 13%, respectively. Optic neuropathy developed in 4 participants (9%) who had received linezolid at a dose of 1200 mg for 26 weeks; all the cases resolved. Six of the seven unfavorable microbiologic outcomes through 78 weeks of follow-up occurred in participants assigned to the 9-week linezolid groups.ConclusionsA total of 84 to 93% of the participants across all four bedaquiline-pretomanid-linezolid treatment groups had a favorable outcome. The overall risk-benefit ratio favored the group that received the three-drug regimen with linezolid at a dose of 600 mg for 26 weeks, with a lower incidence of adverse events reported and fewer linezolid dose modifications. (Funded by the TB Alliance and others; ZeNix ClinicalTrials.gov number, NCT03086486.).

Project description:BackgroundDespite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB.Methods and findingsWe developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of 720 dollars per QALY (8,700 dollars per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of 990 dollars per QALY (12,000 dollars per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of 11,000 dollars per QALY (160,000 dollars per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission.ConclusionsTreatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.

Project description:Mycobacterium tuberculosis develops spontaneous resistance mutants to virtually every drug in use. Courses of therapy select for these mutants and drug-resistant organisms emerge. The development of drug-resistant organisms has reached the point that drug resistance now threatens to undermine global success against tuberculosis (TB). New drugs are needed. The last new class of drugs specifically developed for treatment of TB was the rifamycins over 40 years ago. New funding sources and the development of product development partnerships have energized the TB drug development effort. There are now more TB drugs in development than at any time in the past. The first of these drugs to be developed and marketed was bedaquiline. Bedaquiline has an entirely novel mechanism of action and so should be active against otherwise highly resistant organisms. It acts on the transmembrane component of adenosine triphosphate synthase and acts by preventing electron transport. This raises the exciting possibility that bedaquiline may be active against less metabolically active organisms. Drug-drug interactions between rifamycins and the cytochrome P450-3A system will limit bedaquiline's utility and create complexity in treatment regimens. In clinical trials, treatment with bedaquiline added to a background multidrug-resistant TB regimen was associated with earlier culture conversion and higher cure rates, but there were unexplained excess deaths in the bedaquiline arms of these trials. Food and Drug Administration approved bedaquiline for the treatment of multidrug-resistant TB when an effective treatment regimen cannot otherwise be provided. They required a black box warning about excess deaths and require that a phase III trial be completed. A planned Phase III trial is being reorganized. While bedaquiline is an exciting drug and marks a dramatic moment in the history of TB treatment, its ultimate place in the anti-TB drug armamentarium is unclear pending the Phase III trial and the development of other new drugs that are in the pipeline.

Dataset Information

Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

Objective

Methods

Results

Conclusions

Publications

Cost-effectiveness of adding bedaquiline to drug regimens for the treatment of multidrug-resistant tuberculosis in the UK.

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