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

Abstract

Rationale: 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.

Objectives: To evaluate the costs and cost-effectiveness of regimens for the treatment of LTBI.

Methods: 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.

Measurements and main results: 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.

Conclusions: 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.

Figure 1.

Schematic diagram of model showing the Markov node (labeled “M”). ^aAll patients on the “no treatment” arm start in the “off treatment” branch. ^bPatients whose treatment is complete or who stop due to toxicity or nonadherence return to the “off treatment” branch; patients who will continue treatment return to the “on treatment” branch.

Figure 2.

Cost-effectiveness plots for each of the four regimens plus no treatment under different relative risk of disease activation. (A) Costs and effectiveness for the base-case lifetime risk (6%). In this scenario, rifampin daily for 4 months (4R) is less expensive and more effective than all regimens except isoniazid plus rifapentine weekly for 3 months (3HP), which is more effective at a cost of $48,997 per quality-adjusted life-year (QALY) (shown in the figure as the inverse slope of the solid line connecting 4R and 3HP). 3HP is more effective than 9H, at a cost of $20,207 per QALY (dotted line). (B) The same plot in patients with double the relative risk of activation. In this scenario, 4R and 3HP dominate other options, and 3HP is more effective than 4R, at a cost of $20,099 per QALY (solid line). (C) The plot for patients with relative risk of disease 5.2 times the baseline. Here, 4R and 3HP are equivalent in cost, but 3HP is more effective. (D) The plot for patients with 10 times the relative risk of disease. 3HP dominates all strategies.