Cost-utility analysis of caspofungin and fluconazole for primary treatment of invasive candidiasis and candidemia in Ethiopia
Authors: Gebretekle Gebremedhin Beedemariam , Fentie Atalay Mulu , Gebremariam Girma Tekle , Ali Eskinder Eshetu , Erku Daniel Asfaw , Alemayehu Tinsae , Abebe Workeabeba , Sander Beate 
Published: October 2022

Abstract
Background
Invasive candidiasis and/or candidemia (IC/C) is a common fungal infection leading to significant health and economic losses worldwide. Caspofungin was shown to be more effective than fluconazole in treating inpatients with IC/C. However, cost-effectiveness of caspofungin for treating IC/C in Ethiopia remains unknown. We aimed to assess the cost-utility of caspofungin compared to fluconazole-initiated therapies as primary treatment of IC/C in Ethiopia.

Methods
A Markov cohort model was developed to compare the cost-utility of caspofungin versus fluconazole antifungal agents as first-line treatment for adult inpatients with IC/C from the Ethiopian health system perspective. Treatment outcome was categorized as either a clinical success or failure, with clinical failure being switched to a different antifungal medication. Liposomal amphotericin B (L-AmB) was used as a rescue agent for patients who had failed caspofungin treatment, while caspofungin or L-AmB were used for patients who had failed fluconazole treatment. Primary outcomes were expected quality-adjusted life years (QALYs), costs (US$2021), and the incremental cost-utility ratio (ICUR). These QALYs and costs were discounted at 3% annually. Cost data was obtained from Addis Ababa hospitals while locally unavailable data were derived from the literature. Cost-effectiveness was assessed against the recommended threshold of 50% of Ethiopia’s gross domestic product/capita (i.e.,US$476). Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the findings.

Results
In the base-case analysis, treatment of IC/C with caspofungin as first-line treatment resulted in better health outcomes (12.86 QALYs) but higher costs (US$7,714) compared to fluconazole-initiated treatment followed by caspofungin (12.30 QALYs; US$3,217) or L-AmB (10.92 QALYs; US$2,781) as second-line treatment. Caspofungin as primary treatment for IC/C was not cost-effective when compared to fluconazole-initiated therapies. Fluconazole-initiated treatment followed by caspofungin was cost-effective for the treatment of IC/C compared to fluconazole with L-AmB as second-line treatment, at US$316/QALY gained. Our findings were sensitive to medication costs, drug effectiveness, infection recurrence, and infection-related mortality rates. At a cost-effectiveness threshold of US$476/QALY, treating IC/C patient with fluconazole-initiated treatment followed by caspofungin was more likely to be cost-effective in 67.2% of simulations.

Conclusion
Our study showed that the use of caspofungin as primary treatment for IC/C in Ethiopia was not cost-effective when compared with fluconazole-initiated treatment alternatives. The findings supported the use of fluconazole-initiated therapy with caspofungin as a second-line treatment for patients with IC/C in Ethiopia.