Análise de custo efetividade do tratamento antifúngico empírico de pacientes oncológicos com neutropenia febril
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Data
2022-02-25
Autores
Maza, Lariza
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Universidade Estadual Paulista (Unesp)
Resumo
A neutropenia febril (NF) é uma complicação comum em pacientes com câncer submetidos à quimioterapia. Entre as causas de NF encontram-se as infecções fúngica inasivas (IFI), cujo diagnóstico representa um grande desafio na atualidade, pois os métodos clássicos têm baixa sensibilidade e elevado tempo para obtenção do resultado e a pesquisa de biomarcadores ainda são restritas no Brasil devido a limitação de recursos na saúde pública. Desta forma, a terapia antifúngica empírica é a principal forma de manejo clínico da NF na maioria dos hospitais e o fluconazol, por seu baixo custo direto, é o antifúngico mais utilizado. No entanto, evidências mais recentes trazem que as equinocandinas tem efetividade superior. Com o objetivo de avaliar a incorporação desta classe de antifúngicos no tratamento empírico da NF no sistema público de saúde do Brasil, foi conduzido um estudo de custo-efetividade comparando fluconazol e micafungina em uma coorte retrospectiva de 106 pacientes com diagnóstico de câncer submetidos a quimioterapia, internados em um hospital público da cidade de Bauru, interior do Estado de São Paulo, Brasil, no período de 01 de janeiro de 2015 a 31 de dezembro de 2020. O estudo foi realizado sob as perspectivas do hospital e do Sistema Único de Saúde (SUS) do Brasil e utilizado um horizonte temporal de um ano. Dois cenários clínicos foram avaliados: 1) pacientes com contagem de neutrófilos periféricos menor ou igual a 500 células/mm³ e uso de antibióticos de amplo espectro por ao menos quatro dias (cenário clínico 1); 2) um subgrupo do cenário clínico 1, com maior risco de IFI, formado por pacientes que apresentavam NF com duração mínima de 7 dias (cenário clínico 2). A efetividade do tratamento antifúngico foi medida pelo sucesso terapêutico, caracterizado pela obtenção de cinco quesitos: 1) sobrevida de sete dias após o término do tratamento; 2) ausência de nova IFI neste período; 3) resolução da IFI inicial quando diagnosticada; 4) resolução da febre; 5) não descontinuação prematura do antifúngico por toxicidade ou falta de eficácia. Adotou-se a árvore de decisão como modelo analítico com cálculo da razão incremental de custo-efetividade (RCEI) e análise de sensibilidade. No cenário clínico 1, não se observou diferença de efetividade do tratamento com micafungina versus fluconazol (61,1 vs 45,5%, p=0,22) ao contrário do observado no cenário clínico 2, em que a micafungina foi mais efetiva (71,4 vs 36,1%, p=0,01). A micafungina foi mais efetiva que o fluconazol nos casos em que IFI foi confirmada tanto no cenário clínico 1 (100,0 vs 30,7%, p<0,01) quanto no 2 (100,0 vs 23,5%, p=0,01). Na perspectiva do hospital, a RCEI para micafungina obtida no cenário clínico 1 foi de 25.514,55 R$/sucesso terapêutico (–3.655,22 – 658.255,14) e no 2 de 2.093,51 R$/sucesso terapêutico (–2.335,15 a 504.962,14). Na perspectiva do SUS, a RCEI para micafungina foi de 27.821,28 R$/sucesso terapêutico (–8.312,86 – 634.481,42) no cenário clínico 1 e de 5.499,57 R$/sucesso terapêutico (–6.794,75 – 309.968,85) no cenário 2. Este estudo demonstra que a micafungina pode ser custo-efetiva, considerando a disposição a pagar pelo sistema público de saúde do Brasil, principalmente em pacientes com neutropenia e febre por ao menos sete dias.
Febrile neutropenia (NF) is a common complication in cancer patients undergoing chemotherapy. Among the causes of NF are invasive fungal infections (IFI), whose diagnosis represents a great challenge today, as the classic methods have low sensitivity and long time to obtain the result and the research of biomarkers is still restricted in Brazil due to the limitation of resources in public health. Thus, empirical antifungal therapy is the main form of clinical management of NF in most hospitals and fluconazole, due to its low direct cost, is the most used antifungal. However, more recent evidence shows that echinocandins have superior effectiveness. With the objective of evaluating the incorporation of this class of antifungals in the empirical treatment of NF in the Brazilian public health system, a costeffectiveness study was conducted comparing fluconazole and micafungin in a retrospective cohort of 106 patients diagnosed with cancer undergoing chemotherapy, admitted to a public hospital in the city of Bauru, in the interior of the State of São Paulo, Brazil, from January 1, 2015, to December 31, 2020. The study was carried out from the perspectives of the hospital and the Unified Health System (SUS) in Brazil and a time horizon of one year was used. Two clinical scenarios were evaluated: 1) patients with peripheral neutrophil counts less than or equal to 500 cells/mm³ and use of broad-spectrum antibiotics for at least four days (clinical scenario 1); 2) a subgroup of clinical scenario 1, with a higher risk of IFI, formed by patients who had NF lasting at least 7 days (clinical scenario 2). The effectiveness of the antifungal treatment was measured by the therapeutic success, characterized by the achievement of five criteria: 1) survival of seven days after the end of the treatment; 2) absence of a new IFI in this period; 3) resolution of initial IFI when diagnosed; 4) resolution of fever; 5) nonpremature discontinuation of the antifungal drug due to toxicity or lack of efficacy. The decision tree was adopted as an analytical model with calculation of the incremental cost-effectiveness ratio (ICER) and sensitivity analysis. In clinical scenario 1, there was no difference in the effectiveness of treatment with micafungin versus fluconazole (61.1 vs 45.5%, p=0.22), contrary to what was observed in clinical scenario 2, in which micafungin was more effective (71.4 vs 36.1%, p=0.01). Micafungin was more effective than fluconazole in cases where IFI was confirmed both in clinical scenario 1 (100.0 vs 30.7%, p<0.01) and in clinical scenario 2 (100.0 vs 23.5%, p =0.01). From the hospital perspective, the ICER for micafungin obtained in clinical scenario 1 was 25,514.55 R$/therapeutic success (–3,655.22 – 658,255.14) and in 2,093.51 R$/therapeutic success (–2,335, 15 to 504,962.14). From the SUS perspective, the ICER for micafungin was 27,821.28 BRL/therapeutic success (–8,312.86 – 634,481.42) in clinical scenario 1 and 5,499.57 BRL/therapeutic success (–6,794.75 – 309,968 ,85) in scenario 2. This study demonstrates that micafungin can be costeffective, considering the willingness to pay by the Brazilian public health system, especially in patients with neutropenia and fever for at least seven days
Febrile neutropenia (NF) is a common complication in cancer patients undergoing chemotherapy. Among the causes of NF are invasive fungal infections (IFI), whose diagnosis represents a great challenge today, as the classic methods have low sensitivity and long time to obtain the result and the research of biomarkers is still restricted in Brazil due to the limitation of resources in public health. Thus, empirical antifungal therapy is the main form of clinical management of NF in most hospitals and fluconazole, due to its low direct cost, is the most used antifungal. However, more recent evidence shows that echinocandins have superior effectiveness. With the objective of evaluating the incorporation of this class of antifungals in the empirical treatment of NF in the Brazilian public health system, a costeffectiveness study was conducted comparing fluconazole and micafungin in a retrospective cohort of 106 patients diagnosed with cancer undergoing chemotherapy, admitted to a public hospital in the city of Bauru, in the interior of the State of São Paulo, Brazil, from January 1, 2015, to December 31, 2020. The study was carried out from the perspectives of the hospital and the Unified Health System (SUS) in Brazil and a time horizon of one year was used. Two clinical scenarios were evaluated: 1) patients with peripheral neutrophil counts less than or equal to 500 cells/mm³ and use of broad-spectrum antibiotics for at least four days (clinical scenario 1); 2) a subgroup of clinical scenario 1, with a higher risk of IFI, formed by patients who had NF lasting at least 7 days (clinical scenario 2). The effectiveness of the antifungal treatment was measured by the therapeutic success, characterized by the achievement of five criteria: 1) survival of seven days after the end of the treatment; 2) absence of a new IFI in this period; 3) resolution of initial IFI when diagnosed; 4) resolution of fever; 5) nonpremature discontinuation of the antifungal drug due to toxicity or lack of efficacy. The decision tree was adopted as an analytical model with calculation of the incremental cost-effectiveness ratio (ICER) and sensitivity analysis. In clinical scenario 1, there was no difference in the effectiveness of treatment with micafungin versus fluconazole (61.1 vs 45.5%, p=0.22), contrary to what was observed in clinical scenario 2, in which micafungin was more effective (71.4 vs 36.1%, p=0.01). Micafungin was more effective than fluconazole in cases where IFI was confirmed both in clinical scenario 1 (100.0 vs 30.7%, p<0.01) and in clinical scenario 2 (100.0 vs 23.5%, p =0.01). From the hospital perspective, the ICER for micafungin obtained in clinical scenario 1 was 25,514.55 R$/therapeutic success (–3,655.22 – 658,255.14) and in 2,093.51 R$/therapeutic success (–2,335, 15 to 504,962.14). From the SUS perspective, the ICER for micafungin was 27,821.28 BRL/therapeutic success (–8,312.86 – 634,481.42) in clinical scenario 1 and 5,499.57 BRL/therapeutic success (–6,794.75 – 309,968 ,85) in scenario 2. This study demonstrates that micafungin can be costeffective, considering the willingness to pay by the Brazilian public health system, especially in patients with neutropenia and fever for at least seven days
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neutropenia febril, micafungina,, fluconazol,, custo-efetividade,, terapia empírica.