Economic Analysis of Posaconazole Prophylaxis in Patients with Acute Myeloid Leukemia Undergoing Remission Induction Chemotherapy from a Hospital Management Perspective

Introduction

Invasive fungal infections (IFI) are an important and trending causes of mortality in patients with acute leukemia. Especially during the remission induction, as well as stem cell transplantation, the patients bear the highest risk of IFI due to the prolonged severe neutropenia, long term exposure to broad spectrum antibiotics and cytotoxic chemotherapy.

In a meta analysis of primary antifungal prophylaxis (PAT) in patients with malignancy receiving cytotoxic treatment and/or stem cell transplantation, antifungal prohylaxis was related with dramatic decrease in infection related mortality and decreased IFI. In another meta analysis focusing on prophylaxis with mould-active agents or fluconazole in hematologic malignancies has reported a significant decrease in IFI proven or probable, IFI related mortality and also with a concern, increased risk of adverse effects in the mould-active receiving group.

Patients and Methods

225 patients who have been diagnosed with acute myeloid leukemia (AML) and undergoing intensive treatment (idarubicin 12mg/m2 for three days and cytarabin 100mg/m2 24 h infusion for 7 days) for remission induction have been enrolled in the study in a retrospective manner. Direct health expenses like days of hospitalization, number of CT scans for thorax, development of complications, number of platelet apheresis infusions, mortality during remission induction treatment and total inpatient hospital costs. The benefits included cost reductions after adoption of primary antifungal prophylaxis.

Results

124 patients were male (55,4%) while 100 were female (44,6%). 90 patients received prophylactic treatment during remission induction therapy (40,2%). 43 patients died during remission induction therapy (19,2%). Mean number of thorax CT scans during remission induction was 1,73 (0-6). Mean number of days for hospitalization was 29,36 (14-88) days. Mean number of units of transfused thrombocyte apheresis was 9,9 (0-43) units. Mean cost of whole remission induction treatment was 9.151,6 (2.872,6-20.483,3) US dolars. Within patients who are not on PAT, 116 patients (86,5%) were treated with an intravenous antimould antifungal treatment while 5 of the patients on PAT (5,5%) received parenteral antimould antifungal treatment, 4 of which were related with neutropenic enterocolitis (p<0.005). 32 of the patients who are not on PAT died during remission induction (23,88%) while 11 of the patients who are on PAT died during remission induction (12,22%) (p=0.021). Mean days of hospitalization for remission induction treatment was 22,61 days for patients on PAT and 33,89 days for patients who are not on PAT (p<0.005). In patients on PAT, mean number of transfused platelet units was 6 (0-9) while 12,51 (4-43) units for patients who are not on PAT (p<0.005). When grouped as paients who are and who are not on PAT, there were significant difference between groups regarding total days of hospitalization, number of transfused platelet apheresis units, number of CT scans for thorax, death during remission induction and total cost of remission induction treatment in favor of patients on PAT. All significant data were analyzed with logistic regression analysis and observed as statistically significant. Results were summarized in Table.

Discussion

In Turkey, social security covers all the treatment for malignancies and complications, with rules and statements that lead the clinicians for decisions. Health Application Communiqué regulates the practice for reimbursement and since 2010, antimould antifungal agents are approved for prophylaxis in patients with AML who are undergoing remission induction therapy or patients undergoing hematopoietic stem cell transplantation. According to the physicians' or center's practices, PAT may be used and reimbursed.

In our study, oral suspension form of posaconazole was effective to prevent IFI with a significant decrease in mortality during remission induction treatment. Likewise, PAT with posaconazole was observed to be cost-beneficial regarding the number of CT scans for thorax, number of platelet transfusion and over all costs of hospitalization for remission induction treatment. With its limitations regarding adherence as oral suspension form, tablet form may overcome these limitations.

Table

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Table

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