Short-course amphotericin is cost-effective for cryptococcal meningitis

By Andrew Czyzewski, medwireNews Reporter

medwireNews: The treatment of cryptococcal meningitis (CM) in resource-limited settings is most effective with a short 1-week course of amphotericin induction therapy coupled with high-dose fluconazole for at least 2 weeks, a Ugandan study suggests.

Study co-author David Boulware (University of Minnesota, Minneapolis, USA) and colleagues say their analysis is "generalizable to sub-Saharan African countries" and that switching to this regimen "could save 150,000 lives annually at a cost of US$ 6220 per life saved."

Around 960,000 people each year are infected with CM worldwide (75% in sub-Saharan Africa) and approximately 625,000 (65%) of these people die within 3 months of infection.

The 2011 World Health Organization guidelines recommend induction treatment with a 2-week regimen of intravenous amphotericin B with oral flucytosine (5FC).

However, many stakeholders instead rely on fluconazole monotherapy because it is more accessible, has lower upfront costs, and lacks the lab monitoring requirements of amphotericin treatment - despite having a 25-30% absolute higher mortality.

In the current study, Boulware et al performed a cost-effectiveness analysis of six CM induction regimens each given over a 14-day period: fluconazole monotherapy(800-1200 mg/day); fluconazole (1200 mg/day) plus 5FC (100 mg/kg per day); short-course amphotericin (1 mg/kg per day) for 7 days plus fluconazole (1200 mg per day) for 14 days; amphotericin alone (0.7-1.0 mg/kg per day); amphotericin (0.7-1.0 mg/kg per day) plus fluconazole (800 mg/day); and amphotericin (0.7-1.0 mg/kg per day) plus 5FC (100 mg/kg per day).

Using actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries, the researchers calculated quality-adjusted life years (QALYs) for each regimen.

The cost of hospital care ranged from US$ 154 (€ 119) for fluconazole monotherapy to US$ 467 (€ 361) for 14 days of amphotericin with 5FC.

Based on 18 studies investigating outcomes for HIV-infected individuals with CM, the estimated mean one-year survival was lowest for fluconazole monotherapy at 40% and highest for short-course amphotericin with fluconazole at 65%.

Meanwhile, the cost-effectiveness ratio ranged from US$ 20 (€ 15) per QALY for short-course amphotericin with fluconazole to US$ 44 (€ 34) per QALY for amphotericin plus 5FC.

Thus, overall, the most favorable treatment appeared to be short-course amphotericin with fluconazole, with an incremental cost-effectiveness ratio of US$ 15 (€ 12) per additional QALY over fluconazole monotherapy.

"If the results of this study hold up in further trials, the use of long-course amphotericin-based treatment-expensive and difficult to sustain in resource-limited settings-could be minimized, and a billion dollars spread over 30 or so years supporting short-course amphotericin-based treatment could buy nearly 5 million lives in sub-Saharan Africa," said Andrew Farlow (University of Oxford, UK) in an accompanying comment.

He added: "By any threshold, this would be highly cost-effective. If amphotericin became more affordable, the cost would be lower still."

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