Potential economic viability of two proposed rifapentine-based regimens for treatment of latent tuberculosis infection

David P Holland, Gillian D Sanders, Carol D Hamilton, Jason E Stout, David P Holland, Gillian D Sanders, Carol D Hamilton, Jason E Stout

Abstract

Rationale: Rifapentine-based regimens for treating latent tuberculosis infection (LTBI) are being considered for future clinical trials, but even if they prove effective, high drug costs may limit their economic viability.

Objectives: To inform clinical trial design by estimating the potential costs and effectiveness of rifapentine-based regimens for treatment of latent tuberculosis infection (LTBI).

Methods: We used a Markov model to estimate cost and societal benefits for three regimens for treating LTBI: Isoniazid/rifapentine daily for one month, isoniazid/rifapentine weekly for three months (self-administered and directly-observed), and isoniazid daily for nine months; a strategy of "no treatment" used for comparison. Costs, quality-adjusted life-years gained, and instances of active tuberculosis averted were calculated for all arms.

Results: Both daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months were less expensive and more effective than other strategies under a wide variety of clinically plausibly parameter estimates. Daily isoniazid/rifapentine for one month was the least expensive and most effective regimen.

Conclusions: Daily isoniazid/rifapentine for one month and weekly isoniazid/rifapentine for three months should be studied in a large-scale clinical trial for efficacy. Because both regimens performed well even if their efficacy is somewhat reduced, study designers should consider relaxing non-inferiority boundaries.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Cost-effectiveness plot of the four…
Figure 1. Cost-effectiveness plot of the four regimens and the “no treatment” strategy.
Incremental cost-effectiveness ratios (ICER) are represented by the inverse slope of the dotted and dashed lines between strategies. Abbreviations: 9H = isoniazid daily for 9 months, 3HP = isoniazid plus rifapentine weekly for 3 months, 1HP = isoniazid plus rifapentine daily for 1 month. SAT = self-administered therapy, DOT = directly-observed therapy.
Figure 2. Two-way sensitivity analysis strategy graph…
Figure 2. Two-way sensitivity analysis strategy graph comparing risk reduction and adherence for isoniazid/rifapentine daily for one month (1HP).
The clear area shows combinations of adherence and risk reduction for 1HP that are high enough that 1HP is a cost-saving regimen. In the cross-hatched area, all combinations of adherence and risk reduction for 1HP are too low, so isoniazid/rifapentine monthly for 12 weeks self-administered (3HP-SAT) is preferred regimen.
Figure 3. Two-way sensitivity analysis strategy graph…
Figure 3. Two-way sensitivity analysis strategy graph comparing adherence for isoniazid/rifapentine daily for one month (1HP) vs. isoniazid/rifapentine weekly for three months self-administered (3HP-SAT).
In the diagonal cross-hatched area, 1HP is cost-saving and therefore the preferred regimen. In the horizontal cross-hatched area, 3HP-SAT is cost-saving. In the shaded area, neither regimen is cost-saving when compared to isoniazid monotherapy daily for nine months (9H), which is the preferred regimen.

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