Economic Evaluation of Oral Ivermectin, Alone or in Combination with Permethrin, versus Permethrin, in the Treatment of Classic Scabies in the Philippine Setting

Abstract

Background and objective: Oral ivermectin is recommended as an alternative to topical permethrin in Japanese, European, and CDC-STI guidelines for treating classic scabies. The combination of oral ivermectin and topical permethrin is also used in some settings. Partial economic evaluations conducted in India and Egypt have conflicting results, and no cost-effectiveness analysis in the Philippines has compared ivermectin-based regimens to permethrin for scabies treatment. We aimed to determine the cost-effectiveness of oral ivermectin, alone or in combination with permethrin, compared to permethrin, in the treatment of Filipino adult patients with classic scabies.

Methods: We used a decision tree model to estimate the cost-effectiveness of two regimens, oral ivermectin alone or in combination with permethrin, compared with permethrin to treat adults and children aged five years and older with classic scabies in the outpatient setting from the household perspective in the Philippines. We estimated total costs and disability-adjusted life years (DALYs) over a one-month follow-up. Input parameters were obtained from secondary data, such as effect estimates for probabilities of clinical outcomes from a network meta-analysis, DALYs from the Global Burden of Disease 2019, and prevailing market cost in the Philippines (DPRI 2022 with recommended markup by DOH, and leading drugstores) as of August 2022. We computed for incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) to determine which of the interventions are cost-effective. Univariate and probabilistic sensitivity analyses, and scenario analyses were conducted to assess the impact of parameter and structural uncertainty.

Results: Ivermectin-based regimens are suggested to be likely cost-saving compared to permethrin in the Philippine outpatient setting. Base case analysis showed that oral ivermectin had higher cost-savings (change in cost, -1,039.31; change in DALYS, 0.00027), while combination oral ivermectin/permethrin had higher DALYs averted (change in cost, PhP -1,019.78; change in DALYs, 0.00045), compared to permethrin. Combination oral ivermectin/permethrin (56%) was the most cost-effective, followed by oral ivermectin (44%) compared to permethrin (0%) through probabilistic sensitivity analysis. Estimates for ivermectin were sensitive to risk of cure for ivermectin vs permethrin using 1-way deterministic sensitivity analysis. Oral ivermectin was favored over combination oral ivermectin/permethrin at all thresholds based on the cost-effectiveness acceptability curve.

Conclusion: Both ivermectin-based regimens seem to be cost-saving compared to permethrin in the treatment of classic scabies in the Philippine outpatient setting. Clinicians may consider oral ivermectin, alone or in combination with permethrin as an alternative first-line or second-line treatment depending on patient preference, adverse event risk profile, availability, and economic capacity. This needs to be confirmed using primary data from Filipino patients to enhance the robustness of the findings and support evidence-based local decision-making in different settings. Less uncertainty in modelled parameters can give greater confidence in the results, which can be adopted for budget impact analysis and allow more rational resource allocation. Value of information analysis can be done to determine whether the expense of future RCTs or surveys in Filipinos to collect primary data is worth it. The cost of reducing uncertainty, if deemed worth the cost of further studies, may facilitate population-level decision-making and budget planning. Findings may further inform practice guideline development, coverage decisions, and national control program planning by providing the most cost-effective scabies intervention.

Keywords: cost-effectiveness; economic evaluation; ivermectin; permethrin; scabies.

Figure 1

Decision tree model for scabies treatment. IVM, Ivermectin; Perm, Permethrin; Combi, Combination treatment; AE, Adverse event; DALYs, Disability-adjusted life years. Note: Assumptions and formulas for the model are in Appendix 1.

Figure 2

Cost-effectiveness plane (probabilistic sensitivity analysis). IVM, Ivermectin.

Figure 3

Cost-effectiveness acceptability curve for oral ivermectin vs combination treatment vs permethrin (base case analysis). Perm, Permethrin; IVM, Ivermectin; Combi, Combination.

Figure 4

One-way deterministic sensitivity analysis: Tornado diagram (Ivermectin vs permethrin). rCureIVM, relative risk of cure for oral ivermectin vs permethrin; DALY_Scabies, disability-adjusted life years for scabies; pCurePerm, Probability of cure with permethrin; cTopSter, cost of topical steroids; DALY_Headache, disability-adjusted life years for headache.

Figure 5

One-way deterministic sensitivity analysis: Tornado diagram (Combination therapy vs permethrin). CureCombi, relative risk of cure for combination oral ivermectin/permethrin vs permethrin; DALY_Scabies, disability-adjusted life years for scabies; cTopSter, cost of topical steroids; cPF, cost of professional fee of physician; rAECombi, relative risk of adverse events for combination oral ivermectin/permethrin vs permethrin.

Figure A2.1

Interval plots for network sensitivity analysis splitting the oral ivermectin and permethrin nodes for clinical cure (1 to 2 weeks), all treatments versus two-dose permethrin; random effects. (Data from Genuino et al., 2022).

Figure A2.2

Interval plots for network sensitivity analysis splitting the oral ivermectin and permethrin nodes for adverse events (1 to 2 weeks), all treatments versus two-dose permethrin; random effects. (Data from Genuino et al., 2022).

Figure A3.1

Proportional meta-analysis for permethrin (2-dose) cure rate at 1 to 2 weeks. (Data from Genuino et al., 2022).

Figure A3.2

Proportional meta-analysis for permethrin (2-dose) adverse event rate. (Data from Genuino et al., 2022).

Figure A4.1

Pairwise meta-analysis for adverse events for oral ivermectin vs permethrin (A) main analysis, (B) subgroup by type of adverse event (cutaneous vs systemic). (Data from Genuino et al., 2022).

Figure A4.2

Pairwise meta-analysis for adverse events for combination vs permethrin (A) main analysis, (B) with subgroup by type of adverse event (cutaneous vs systemic). (Data from Genuino et al., 2022).