RESUMO
Introducción Brolucizumab es un nuevo fármaco antifactor de crecimiento endotelial vascular (anti-VEGF) administrado con una pauta fija de ocho o 12 semanas que en los estudios HAWK y HARRIER demostró ser no inferior a aflibercept con respecto a la mejor agudeza visual corregida, bajo una menor carga de administración. El objetivo del análisis fue comparar los costes directos sanitarios de ambos anti-VEGF como tratamiento en pacientes con degeneración macular asociada a la edad neovascular. Material y métodos Se realizó un análisis de minimización de costes bajo un horizonte temporal de 25 años y considerando el coste farmacológico, de administración, de pruebas de seguimiento y del manejo de eventos adversos. El uso de recursos fue obtenido de literatura relacionada y validada por expertos clínicos. Se llevaron a cabo diversos análisis de escenarios para comprobar la robustez de los resultados. Resultados Brolucizumab resultó con un menor coste por paciente en comparación con aflibercept, considerando el número de inyecciones derivadas de los estudios HAWK y HARRIER. Este resultado se mantuvo en los diferentes escenarios analizados, excepto frente al número de inyecciones de la pauta flexible de aflibercept del estudio ARIES, ya que la menor discontinuación de tratamiento con brolucizumab conlleva mantener el tratamiento de más pacientes. Al considerar la misma discontinuación, brolucizumab mantuvo los resultados observados en el caso base del análisis. Conclusiones El presente estudio muestra como la pauta de administración fija de brolucizumab puede ayudar a disminuir la carga asistencial para los centros sanitarios y los pacientes (AU)
Introduction Brolucizumab is a novel anti-vascular endothelial growth factor (anti-VEGF) drug administered in a fixed regimen of 8 or 12 weeks which, in the HAWK and HARRIER studies, was shown not to be inferior to aflibercept with respect to the best corrected visual acuity, with a less burdensome treatment regimen. The aim of the analysis was to compare the direct healthcare costs of both anti-VEGF as a treatment in patients with neovascular age-related macular degeneration.Material and methods A cost minimization analysis was performed under a 25-year time horizon and considering the drug costs, administration, follow-up tests, and management of adverse events. Resource use was obtained from the related literature and validated by clinical experts. Various scenario analysis were carried out to check the robustness of the results. Results Brolucizumab resulted in a lower cost per patient compared with aflibercept, considering the number of injections derived from the HAWK and HARRIER studies. This result was maintained in the different scenarios analysed, except for the number of injections of the flexible aflibercept regimen of the ARIES study, since the lower discontinuation of treatment with brolucizumab implies maintaining the treatment of more patients. Considering the same discontinuation, brolucizumab maintained the results observed in the base case of the analysis. Conclusions This study shows how the fixed administration regimen of brolucizumab can help reduce both healthcare and patients burden (AU)
Assuntos
Custos e Análise de Custo , Inibidores da Angiogênese/economia , Custos de Medicamentos , Injeções IntravítreasRESUMO
INTRODUCTION: Brolucizumab is a novel anti-vascular endothelial growth factor (anti-VEGF) drug administered in a fixed regimen of 8 or 12 weeks which, in the HAWK and HARRIER studies, was shown not to be inferior to aflibercept with respect to the best corrected visual acuity, with a less burdensome treatment regimen. The aim of the analysis was to compare the direct healthcare costs of both anti-VEGF as a treatment in patients with neovascular age-related macular degeneration. MATERIAL AND METHODS: A cost minimization analysis was performed under a 25-year time horizon and considering the drug costs, administration, follow-up tests, and management of adverse events. Resource use was obtained from the related literature and validated by clinical experts. Various scenario analysis were carried out to check the robustness of the results. RESULTS: Brolucizumab resulted in a lower cost per patient compared with aflibercept, considering the number of injections derived from the HAWK and HARRIER studies. This result was maintained in the different scenarios analysed, except for the number of injections of the flexible aflibercept regimen of the ARIES study, since the lower discontinuation of treatment with brolucizumab implies maintaining the treatment of more patients. Considering the same discontinuation, brolucizumab maintained the results observed in the base case of the analysis. CONCLUSIONS: This study shows how the fixed administration regimen of brolucizumab can help reduce both healthcare and patients' burden.
Assuntos
Inibidores da Angiogênese , Degeneração Macular , Humanos , Inibidores da Angiogênese/uso terapêutico , Injeções Intravítreas , Custos e Análise de Custo , Degeneração Macular/tratamento farmacológicoRESUMO
Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.
