Cost-effectiveness of meglumine antimoniate versus miltefosine caregiver DOT for the treatment of pediatric cutaneous leishmaniasis

Abstract

Background: Oral miltefosine has been shown to be non-inferior to first-line, injectable meglumine antimoniate (MA) for the treatment of cutaneous leishmaniasis (CL) in children. Miltefosine may be administered via in-home caregiver Directly Observed Therapy (cDOT), while patients must travel to clinics to receive MA. We performed a cost-effectiveness analysis comparing miltefosine by cDOT versus MA for pediatric CL in southwest Colombia.

Methodology/principle findings: We developed a Monte Carlo model comparing the cost-per-cure of miltefosine by cDOT compared to MA from patient, government payer, and societal perspectives (societal = sum of patient and government payer perspective costs). Drug effectiveness and adverse events were estimated from clinical trials. Healthcare utilization and costs of travel were obtained from surveys of providers and published sources. The primary outcome was cost-per-cure reported in 2015 USD. Treatment efficacy, costs, and adherence were varied in sensitivity analysis to assess robustness of results. Treatment with miltefosine resulted in substantially lower cost-per-cure from a societal and patient perspective, and slightly higher cost-per-cure from a government payer perspective compared to MA. Mean societal cost-per-cure were $531 (SD±$239) for MA and $188 (SD±$100) for miltefosine, a mean cost-per-cure difference of +$343. Mean cost-per-cure from a patient perspective were $442 (SD ±$233) for MA and $30 (SD±$16) for miltefosine, a mean difference of +$412. Mean cost-per-cure from a government perspective were $89 (SD±$55) for MA and $158 (SD±$98) for miltefosine, with a mean difference of -$69. Results were robust across a variety of assumptions in univariate and multi-way analysis.

Conclusions/significance: Treatment of pediatric cutaneous leishmaniasis with miltefosine via cDOT is cost saving from patient and societal perspectives, and moderately more costly from the government payer perspective compared to treatment with MA. Results were robust over a range of sensitivity analyses. Lower drug price for miltefosine could result in cost saving from a government perspective.

Fig 1. Tornado diagram of one-way sensitivity analyses of basic assumptions’ effects on miltefosine cDOT/MA cost ratio.

Model parameters are listed on the vertical axis, with the range examined in sensitivity analyses in parentheses. The length of the horizontal bar demonstrates the impact of the changes in the parameter values on the cost ratio of miltefosine cDOT to MA. The solid vertical line indicates the estimated cost ratio of the base case. For example, an adherence rate of 100% was assumed for the miltefosine cDOT program in the base case. The cost ratio favored miltefosine cDOT for all simulated scenarios. *inverse of failure due to non-adherence, ^abase case is WHO price. cDOT: caregiver directly observed therapy, MA: meglumine antimoniate, WHO: World Health Organization.

Fig 2. Tornado diagram of one-way sensitivity analyses of effect on miltefosine cDOT/MA cost ratio of parameters from survey data.

Model parameters are listed on the vertical axis, with the range examined in sensitivity analyses in parentheses. The length of the horizontal bar demonstrates the impact of the changes in the parameter values on the cost ratio of miltefosine cDOT to MA. The solid vertical line indicates the estimated cost ratio of the base case. For example, a cost of $0 was estimated for the base case for miltefosine supply costs. The cost ratio favored miltefosine cDOT for all simulated scenarios. MA: meglumine antimoniate, cDOT: caregiver directly observed therapy.

Fig 3. Multi-way sensitivity analysis of patient cost, healthcare system cost, drug formulation availability, and effectiveness.

Cost to patients, the healthcare system, drug formulation availability, and effectiveness are varied simultaneously. The solid line represents equivalent efficacy of miltefosine and MA, varied over percent changes in MA-associated cost to patients and miltefosine cDOT-associated cost to the healthcare system. The dotted line represents the rightward shift in the boundary of cost-effectiveness when the effectiveness ratio of miltefosine to MA is increased to 1.19, as calculated from the upper bound of the miltefosine cure rate 95% CI divided by the lower bound of the MA cure rate 95% CI from the clinical trials. The hatched line represents the leftwards shift in the boundary of cost-effectiveness when the effectiveness ratio of miltefosine to MA is decreased to 0.81, calculated by subtracting the reciprocal change from baseline assumption. A diamond at the origin represents the mean case as calculated by the Monte Carlo model. MA: meglumine antimoniate; cDOT: caregiver directly observed therapy.