Recomendaciones para el tratamiento oral de pacientes adultos con enfermedad de Gaucher tipo 1 / Recommendations for oral treatment for adult patients with type 1 Gaucher disease

Revisión de la evidencia científica sobre el tratamiento oral de pacientes adultos con enfermedad de Gaucher tipo 1 (EG1), con formato de guía clínica, según la normativa Agree II. Se describen las principales diferencias entre los 2 tratamientos orales disponibles actualmente para el tratamiento de esta entidad (miglustat y eliglustat).En esta revisión se recuerda que los criterios para iniciar el tratamiento oral en los pacientes con EG1 deben valorarse de forma individualizada. Si bien miglustat y eliglustat son inhibidores de la enzima glucosilceramida sintetasa, los 2 presentan diferentes mecanismos de acción y propiedades farmacológicas y nunca se deben considerar como equivalentes. Miglustat está indicado en pacientes con EG1 no grave que no pueden recibir otro tratamiento de primera línea, mientras que eliglustat está indicado en pacientes con EG1 con cualquier gravedad, en primera línea y sin necesidad de estabilización previa con tratamiento de reemplazo enzimático. Es importante enfatizar que para iniciar tratamiento con eliglustat debemos conocer el fenotipo metabólico CYP2D6 y que su asociación con fármacos metabolizados a través de los citocromos CYP2D6 y CYP3A4 –o bien que utilicen la glucoproteína P– se debe evaluar individualmente. Durante el embarazo se debe evitar el uso de eliglustat, pudiéndose emplear únicamente el tratamiento de reemplazo enzimático. A diferencia de miglustat, cuyos efectos adversos han limitado su utilización, eliglustat no solo ha demostrado una eficacia similar a la del tratamiento de reemplazo enzimático, sino que ha demostrado mejoría en la calidad de vida de los pacientes EG1. (AU)

This work is a review of the scientific evidence on the oral treatment of adult patients with Gaucher disease type 1 (GD1) with a clinical guideline format according to the Agree II regulations. It describes the main differences between the 2 oral treatments currently available for treating this disease (miglustat and eliglustat).This review reminds us that the criteria for starting oral treatment in patients with GD1 must be assessed individually. Although miglustat and eliglustat are both glucosylceramide synthase enzyme inhibitors, they have different mechanisms of action and pharmacological properties and should never be considered equivalent. Miglustat is indicated in patients with non-severe GD1 who cannot receive other first-line treatments, while eliglustat is indicated as first-line treatment for patients with GD1 of any severity without the need for prior stabilization with enzyme replacement therapy. It is important to emphasize that in order to start treatment with eliglustat, we must know the CYP2D6 metabolic phenotype and its association with drugs metabolized through the CYP2D6 and CYP3A4 cytochromes –or alternatively those that use P-Glycoprotein– must be evaluated on an individual basis. During pregnancy, the use of eliglustat should be avoided; only enzyme replacement therapy can be used. Unlike miglustat, whose adverse effects have limited its use, eliglustat has not only demonstrated similar efficacy to enzyme replacement therapy but has also been shown to improve the quality of life of patients with GD1. (AU)

Recommendations for oral treatment for adult patients with type 1 Gaucher disease.

This work is a review of the scientific evidence on the oral treatment of adult patients with Gaucher disease type 1 (GD1) with a clinical guideline format according to the Agree II regulations. It describes the main differences between the two oral treatments currently available for treating this disease (miglustat and eliglustat). This review reminds us that the criteria for starting oral treatment in patients with GD1 must be assessed individually. Although miglustat and eliglustat are both glucosylceramide synthase (GCS) enzyme inhibitors, they have different mechanisms of action and pharmacological properties and should never be considered equivalent. Miglustat is indicated in patients with non-severe GD1 who cannot receive other first-line treatments, while eliglustat is indicated as first-line treatment for patients with GD1 of any severity without the need for prior stabilization with enzyme replacement therapy (ERT). It is important to emphasize that in order to start treatment with eliglustat, we must know the CYP2D6 metabolic phenotype and its association with drugs metabolized through the CYP2D6 and CYP3A4 cytochromes-or alternatively those that use P-Glycoprotein must be evaluated on an individual basis. During pregnancy, the use of eliglustat should be avoided; only ERT can be used. Unlike miglustat, whose adverse effects have limited its use, eliglustat has not only demonstrated similar efficacy to ERT but has also been shown to improve the quality of life of patients with GD1.