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Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection.

ABSTRACT: Isoniazid given daily for 9 months is the standard treatment for latent tuberculosis infection (LTBI), but its effectiveness is limited by poor completion rates. Shorter course regimens and regimens using directly observed therapy result in improved adherence but have higher upfront costs.To evaluate the costs and cost-effectiveness of regimens for the treatment of LTBI.We used a computerized Markov model to estimate total societal costs and benefits associated with four regimens for the treatment of LTBI: self-administered isoniazid daily for 9 months, directly observed isoniazid twice-weekly for 9 months, directly observed isoniazid plus rifapentine once weekly for 3 months, and self-administered rifampin daily for 4 months. In the base-case analysis, subjects were assumed to have newly positive tuberculin skin tests after recent exposure to infectious tuberculosis.We determined the costs of treatment, quality-adjusted life-years gained, and cases of active tuberculosis prevented. In the base-case analysis, rifampin dominated (less costly with increased benefits) all other regimens except isoniazid plus rifapentine, which was more effective at a cost $48,997 per quality-adjusted life year gained. Isoniazid plus rifapentine dominated all regimens at a relative risk of disease 5.2 times the baseline estimate, or with completion rates less than 34% for isoniazid or 37% for rifampin. Rifampin could be 17% less efficacious than self-administered isoniazid and still be cost-saving compared with this regimen.In our model, rifampin is cost-saving compared with the standard therapy of self-administered isoniazid. Isoniazid plus rifapentine is cost-saving for extremely high-risk patients and is cost-effective for lower-risk patients.

SUBMITTER: Holland DP

PROVIDER: S-EPMC2689913 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection.

Holland David P DP Sanders Gillian D GD Hamilton Carol D CD Stout Jason E JE

American journal of respiratory and critical care medicine 20090319 11

<h4>Rationale</h4>Isoniazid given daily for 9 months is the standard treatment for latent tuberculosis infection (LTBI), but its effectiveness is limited by poor completion rates. Shorter course regimens and regimens using directly observed therapy result in improved adherence but have higher upfront costs.<h4>Objectives</h4>To evaluate the costs and cost-effectiveness of regimens for the treatment of LTBI.<h4>Methods</h4>We used a computerized Markov model to estimate total societal costs and b ...[more]

PMID: 19299495

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Project description:BackgroundShorter, safer, and cheaper tuberculosis (TB) preventive treatment (TPT) regimens will enhance uptake and effectiveness. WHO developed target product profiles describing minimum requirements and optimal targets for key attributes of novel TPT regimens. We performed a cost-effectiveness analysis addressing the scale-up of regimens meeting these criteria in Brazil, a setting with relatively low transmission and low HIV and rifampicin-resistant TB (RR-TB) prevalence, and South Africa, a setting with higher transmission and higher HIV and RR-TB prevalence.Methods and findingsWe used outputs from a model simulating scale-up of TPT regimens meeting minimal and optimal criteria. We assumed that drug costs for minimal and optimal regimens were identical to 6 months of daily isoniazid (6H). The minimal regimen lasted 3 months, with 70% completion and 80% efficacy; the optimal regimen lasted 1 month, with 90% completion and 100% efficacy. Target groups were people living with HIV (PLHIV) on antiretroviral treatment and household contacts (HHCs) of identified TB patients. The status quo was 6H at 2019 coverage levels for PLHIV and HHCs. We projected TB cases and deaths, TB-associated disability-adjusted life years (DALYs), and costs (in 2020 US dollars) associated with TB from a TB services perspective from 2020 to 2035, with 3% annual discounting. We estimated the expected costs and outcomes of scaling up 6H, the minimal TPT regimen, or the optimal TPT regimen to reach all eligible PLHIV and HHCs by 2023, compared to the status quo. Maintaining current 6H coverage in Brazil (0% of HHCs and 30% of PLHIV treated) would be associated with 1.1 (95% uncertainty range [UR] 1.1-1.2) million TB cases, 123,000 (115,000-132,000) deaths, and 2.5 (2.1-3.1) million DALYs and would cost $1.1 ($1.0-$1.3) billion during 2020-2035. Expanding the 6H, minimal, or optimal regimen to 100% coverage among eligible groups would reduce DALYs by 0.5% (95% UR 1.2% reduction, 0.4% increase), 2.5% (1.8%-3.0%), and 9.0% (6.5%-11.0%), respectively, with additional costs of $107 ($95-$117) million and $51 ($41-$60) million and savings of $36 ($14-$58) million, respectively. Compared to the status quo, costs per DALY averted were $7,608 and $808 for scaling up the 6H and minimal regimens, respectively, while the optimal regimen was dominant (cost savings, reduced DALYs). In South Africa, maintaining current 6H coverage (0% of HHCs and 69% of PLHIV treated) would be associated with 3.6 (95% UR 3.0-4.3) million TB cases, 843,000 (598,000-1,201,000) deaths, and 36.7 (19.5-58.0) million DALYs and would cost $2.5 ($1.8-$3.6) billion. Expanding coverage with the 6H, minimal, or optimal regimen would reduce DALYs by 6.9% (95% UR 4.3%-95%), 15.5% (11.8%-18.9%), and 38.0% (32.7%-43.0%), respectively, with additional costs of $79 (-$7, $151) million and $40 (-$52, $140) million and savings of $608 ($443-$832) million, respectively. Compared to the status quo, estimated costs per DALY averted were $31 and $7 for scaling up the 6H and minimal regimens, while the optimal regimen was dominant. Study limitations included the focus on 2 countries, and no explicit consideration of costs incurred before the decision to prescribe TPT.ConclusionsOur findings suggest that scale-up of TPT regimens meeting minimum or optimal requirements would likely have important impacts on TB-associated outcomes and would likely be cost-effective or cost saving.

Project description:The majority of tuberculosis in migrants to Canada occurs due to reactivation of latent TB infection. Risk of tuberculosis in those with latent tuberculosis infection can be significantly reduced with treatment. Presently, only 2.4% of new migrants are flagged for post-landing surveillance, which may include latent tuberculosis infection screening; no other migrants receive routine latent tuberculosis infection screening. To aid in reducing the tuberculosis burden in new migrants to Canada, we determined the cost-effectiveness of using different latent tuberculosis infection interventions in migrants under post-arrival surveillance and in all new migrants.A discrete event simulation model was developed that focused on a Canadian permanent resident cohort after arrival in Canada, utilizing a ten-year time horizon, healthcare system perspective, and 1.5% discount rate. Latent tuberculosis infection interventions were evaluated in the population under surveillance (N = 6100) and the total cohort (N = 260,600). In all evaluations, six different screening and treatment combinations were compared to the base case of tuberculin skin test screening followed by isoniazid treatment only in the population under surveillance. Quality adjusted life years, incident tuberculosis cases, and costs were recorded for each intervention and incremental cost-effectiveness ratios were calculated in relation to the base case.In the population under surveillance (N = 6100), using an interferon-gamma release assay followed by rifampin was dominant compared to the base case, preventing 4.90 cases of tuberculosis, a 4.9% reduction, adding 4.0 quality adjusted life years, and saving $353,013 over the ensuing ten-years. Latent tuberculosis infection screening in the total population (N = 260,600) was not cost-effective when compared to the base case, however could potentially prevent 21.8% of incident tuberculosis cases.Screening new migrants under surveillance with an interferon-gamma release assay and treating with rifampin is cost saving, but will not significantly impact TB incidence. Universal latent tuberculosis infection screening and treatment is cost-prohibitive. Research into using risk factors to target screening post-landing may provide alternate solutions.

Project description:IntroductionActive-case finding (ACF) programs have an important role in addressing case detection gaps and halting tuberculosis (TB) transmission. Evidence is limited on the cost-effectiveness of ACF interventions, particularly on how their value is impacted by different operational, epidemiological and patient care-seeking patterns.MethodsWe evaluated the costs and cost-effectiveness of a combined facility and community-based ACF intervention in Zambia that utilized mobile chest X-ray with computer-aided reading/interpretation software and laboratory-based Xpert MTB/RIF testing. Programmatic costs (in 2018 US dollars) were assessed from the health system perspective using prospectively collected cost and operational data. Cost-effectiveness of the ACF intervention was assessed as the incremental cost per TB death averted over a five-year time horizon using a multi-stage Markov state-transition model reflecting patient symptom-associated care-seeking and TB care under ACF compared to passive care.ResultsOver 18 months of field operations, the ACF intervention costed $435 to diagnose and initiate treatment for one person with TB. After accounting for patient symptom-associated care-seeking patterns in Zambia, we estimate that this one-time ACF intervention would incrementally diagnose 407 (7,207 versus 6,800) TB patients and avert 502 (611 versus 1,113) TB-associated deaths compared to the status quo (passive case finding), at an incremental cost of $2,284 per death averted over the next five-year period. HIV/TB mortality rate, patient symptom-associated care-seeking probabilities in the absence of ACF, and the costs of ACF patient screening were key drivers of cost-effectiveness.ConclusionsA one-time comprehensive ACF intervention simultaneously operating in public health clinics and corresponding catchment communities can have important medium-term impact on case-finding and be cost-effective in Zambia. The value of such interventions increases if targeted to populations with high HIV/TB mortality, substantial barriers (both behavioral and physical) to care-seeking exist, and when ACF interventions can optimize screening by achieving operational efficiency.

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Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection.

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Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection.

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