Budgetary impact of using BPaL for treating extensively drug-resistant tuberculosis.

INTRODUCTION: Bedaquiline, pretomanid and linezolid (BPaL) is a new all oral, 6-month regimen comprised of bedaquiline, the new drug pretomanid and linezolid, endorsed by the WHO for use under operational research conditions in patients with extensively drug-resistant tuberculosis (XDR-TB). We quantified per-patient treatment costs and the 5-year budgetary impact of introducing BPaL in Indonesia, Kyrgyzstan and Nigeria. METHODS: Per-patient treatment cost of BPaL regimen was compared head-to-head with the conventional XDR-TB treatment regimen for respective countries based on cost estimates primarily assessed using microcosting method and expected frequency of each TB service. The 5-year budget impact of gradual introduction of BPaL against the status quo was assessed using a Markov model that represented patient's treatment management and outcome pathways. RESULTS: The cost per patient completing treatment with BPaL was US$7142 in Indonesia, US$4782 in Kyrgyzstan and US$7152 in Nigeria - 57%, 78% and 68% lower than the conventional regimens in the respective countries. A gradual adoption of the BPaL regimen over 5 years would result in an 5-year average national TB service budget reduction of 17% (US$128 780) in XDR-TB treatment-related expenditure in Indonesia, 15% (US$700 247) in Kyrgyzstan and 32% (US$1 543 047) in Nigeria. CONCLUSION: Our study demonstrates that the BPaL regimen can be highly cost-saving compared with the conventional regimens to treat patients with XDR-TB in high drug-resistant TB burden settings. This supports the rapid adoption of the BPaL regimen to address the significant programmatic and clinical challenges in managing patients with XDR-TB in high DR-TB burden countries.

Cost-effectiveness of bedaquiline, pretomanid and linezolid for treatment of extensively drug-resistant tuberculosis in South Africa, Georgia and the Philippines.

OBJECTIVES: Patients with highly resistant tuberculosis have few treatment options. Bedaquiline, pretomanid and linezolid regimen (BPaL) is a new regimen shown to have favourable outcomes after six months. We present an economic evaluation of introducing BPaL against the extensively drug-resistant tuberculosis (XDR-TB) standard of care in three epidemiological settings. DESIGN: Cost-effectiveness analysis using Markov cohort model. SETTING: South Africa, Georgia and the Philippines. PARTICIPANTS: XDR-TB and multidrug-resistant tuberculosis (MDR-TB) failure and treatment intolerant patients. INTERVENTIONS: BPaL regimen. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Incremental cost per disability-adjusted life years averted by using BPaL against standard of care at the Global Drug Facility list price. (2) The potential maximum price at which the BPaL regimen could become cost neutral. RESULTS: BPaL for XDR-TB is likely to be cost saving in all study settings when pretomanid is priced at the Global Drug Facility list price. The magnitude of these savings depends on the prevalence of XDR-TB in the country and can amount, over 5 years, to approximately US$ 3 million in South Africa, US$ 200 000 and US$ 60 000 in Georgia and the Philippines, respectively. In South Africa, related future costs of antiretroviral treatment (ART) due to survival of more patients following treatment with BPaL reduced the magnitude of expected savings to approximately US$ 1 million. Overall, when BPaL is introduced to a wider population, including MDR-TB treatment failure and treatment intolerant, we observe increased savings and clinical benefits. The potential threshold price at which the probability of the introduction of BPaL becoming cost neutral begins to increase is higher in Georgia and the Philippines (US$ 3650 and US$ 3800, respectively) compared with South Africa (US$ 500) including ART costs. CONCLUSIONS: Our results estimate that BPaL can be a cost-saving addition to the local TB programmes in varied programmatic settings.

Clinical Impact of Rapid Drug Susceptibility Testing to Accompany Fluoroquinolone-Containing Universal Tuberculosis Regimens: A Markov Model.

BACKGROUND: To appropriately treat tuberculosis (TB) with regimens that combine novel and older drugs, evidence-based, context-specific strategies for drug-susceptibility testing (DST) will be required. METHODS: We created a Markov state-transition model of 100 000 adults with TB receiving a novel, fluoroquinolone (FQ)-containing regimen. We estimated clinical outcomes and resource utilization with no FQ-DST, universal FQ-DST, or FQ-DST only for patients with rifampin-resistant TB ("targeted FQ-DST"). We considered scenarios of stronger (South Africa) and weaker (Southeast Asia) correlation of fluoroquinolone resistance with rifampin resistance, with sensitivity analysis for other setting and regimen characteristics. RESULTS: Relative to no FQ-DST, targeted FQ-DST increased cure of FQ-resistant TB by 7.5% (interquartile range [IQR], 6.7%-9.2%) in South Africa and 1.7% (IQR, 0.7%-2.5%) in Southeast Asia. However, rare FQ resistance among the more prevalent rifampin-susceptible TB accounted for 50% of FQ-resistant TB in South Africa and 83% in Southeast Asia. As a result, universal FQ-DST further increased cure of FQ-resistant TB by 3.4% (IQR, 2.3%-5.4%) in South Africa and 5.8% (IQR, 5.1%-6.3%) in Southeast Asia. With targeted FQ-DST, 1 additional patient was cured per 50 (IQR, 42-70) tests in South Africa and 44 (IQR, 37-51) in Southeast Asia. When expanding from targeted to universal FQ-DST, 1 additional cure required 3500 (IQR, 2300-5500) tests in South Africa and 410 (IQR, 370-450) in Southeast Asia. CONCLUSIONS: FQ-DST improved patient outcomes and was particularly important for high-risk patient groups and less robust regimens. A universal strategy was favored in generalized epidemics of fluoroquinolone resistance.

Estimating the impact of a novel drug regimen for treatment of tuberculosis: a modeling analysis of projected patient outcomes and epidemiological considerations.

BACKGROUND: Regimens that could treat both rifampin-resistant (RR) and rifampin-susceptible tuberculosis (TB) while shortening the treatment duration have reached late-stage clinical trials. Decisions about whether and how to implement such regimens will require an understanding of their likely clinical impact and how this impact depends on local epidemiology and implementation strategy. METHODS: A Markov state-transition model of 100,000 representative South African adults with TB was used to simulate implementation of the regimen BPaMZ (bedaquiline, pretomanid, moxifloxacin, and pyrazinamide), either for RR-TB only or universally for all patients. Patient outcomes, including cure rates, time with active TB, and time on treatment, were compared to outcomes under current care. Sensitivity analyses varied the drug-resistance epidemiology, rifampin susceptibility testing practices, and regimen efficacy. RESULTS: Using BPaMZ exclusively for RR-TB increased the proportion of all RR-TB that was cured by initial treatment from 60 ± 1% to 67 ± 1%. Expanding use of BPaMZ to all patients increased cure of RR-TB to 89 ± 1% and cure of all TB from 87.3 ± 0.1% to 89.5 ± 0.1%, while shortening treatment by 1.9 months/person. In sensitivity analyses, reducing the coverage of rifampin susceptibility testing resulted in lower projected proportions of patients cured under all regimen scenarios (current care, RR-only BPaMZ, and universal BPaMZ), compared to the proportions projected using South Africa's high coverage; however, this reduced coverage resulted in greater expected incremental benefits of universal BPaMZ implementation, both when compared to RR-only BPaMZ implementation and when compared to to current care under the same low rifampin susceptibility testing coverage. In settings with higher RR-TB prevalence, the benefits of BPaMZ were magnified both for RR-specific and universal BPaMZ implementation. CONCLUSIONS: Novel regimens such as BPaMZ could improve RR-TB outcomes and shorten treatment for all patients, particularly with universal use. Decision-makers weighing early options for implementing such regimens at scale will want to consider the expected impact on patient outcomes and on the burden of treatment in their local context.