I was reading a recent paper from some of my colleagues at Fred Hutchinson Cancer Research Center (FHCRC) from November regarding ICU admission and patients with acute myelogenous leukemia (AML).  Dr. Gary Lyman and his colleagues, looked at hospital records and charges from nearly 50,000 patients from the University HealthSystem Consortium, and looked at risk factors and costs for ICU admission (ref). Not surprisingly one of the most important risk factors for ICU admission: a fungal infection.

While fungal complications of hematologic malignancies continue to be a major problem, data exist that support the use of primary antifungal prophylaxis to prevent these high-risk events.  Such agents are particularly important in high-risk patients with acute myelogenous leukemia, those with myelodysplastic syndrome, and hematopoietic cell transplant (HCT) recipients treated for graft-versus-host disease. The triazole posaconazole has been shown to be effective at limiting fungal infections in these patients in a large randomized trial that is nearly 10 years old now (ref & ref).  Yet, the use of this drug and others in its class isn’t universal.  

The downside to such therapy has been eye-popping costs of these agents – if not covered by insurance,  oral posaconazole tablets out-of-pocket costs lean upwards of $5500 US a month (or $183 US a day).  In those already pressed by the financial insecurity of cancer therapy, many may be forced to make a choice between paying their bills at home to keep the lights on or taking a preventative medication for short term security.  Unfortunately, chemotherapy is repetitive in these patients as is prolonged neutropenia and ongoing immunosuppression.  Most patients require months of antifungals and hence increased cost.  Some sacrifice, by moving to less expensive and less effective agents (e.g. fluconazole prophylaxis which does not provide adequate mold coverage).  Others use voriconazole, which failed (for a number of reasons) as a prevention strategy in a randomized-double blind trial when compared to fluconazole in allogeneic bone marrow transplant recipients (ref), and itself although generic, is over $130 US a day (ref).  

fungal_2
A patient with Aspergillus pneumonia – which can cost upwards of $70,000 per episode

The downside of saving short term dollars on antifungal therapy, is that for patients who go one to develop fungal infections the situation becomes even more costly – aspergillosis for example is estimated to costs over $70,000 per event (ref).   Fungal infections increase the risk of ICU admission, by nearly 25% as shown in the study by Dr. Lyman and his colleagues, and therefore burden patients with increased hospitals costs and excess morbidity (ref). More importantly, mortality for aspergillosis despite improvements in therapy is still substantial, and death from rare fungi such as the Mucorales spp. and Fusarium spp. are even more likely.  Antifungals prophylaxis cannot prevent all major fungal pathogens, but the use of prophylaxis remains once of the most important form of prevention and one of the only we have in our quiver.

So how does one help patients make the choice – or perhaps better phrased – how do we prevent patients/providers from having to make a choice at all?   Can we get insurance companies to cover these critical agents?  How might we find alternate ways for those without adequate coverage?  Patient assistance programs are important options, but aren’t sufficient, and they don’t help everyone.  More worrisome, changes in the Affordable Care Act might cause an even further shift even away from prevention to more costly treatment.  As we continue to ask patients, or in some cases hospitals to foot the bill, we will continue to limit the use of antifungal prophylaxis for those who need it most.

While I don’t believe posaconazole or any antifungal prophylaxis is a panacea, their clear benefits make such cost decisions unfair for patients and providers.  This paper adds the burden of data that calls out for efforts to tackle this challenging problem.

Reference:  Halpern AB, et al. Association of Risk Factors, Mortality, and Care Costs of Adults with Acute Myeloid Leukemia with Admission to the Intensive Care Unit. JAMA Oncology. 2016 Nov 10 (epub) (Link)

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