Siponimod (BAF312): Características generales e implicancias clínicas de la dosificación farmacogenómica en el tratamiento de la Esclerosis Múltiple secundaria progresiva / Siponimod (BAF312): General Characteristics and Clinical Implications of Pharmacogenomic Dosage in the Treatment of Active Secondary Progressive Multiple Sclerosis

Siponimod es un medicamento inmunosupresor selectivo, desarrollado como la primera terapia oral para la esclerosis múltiple secundaria progresiva activa. Este medicamento actúa modulando el receptor de esfingosina 1 fosfato (S1P), como antagonista de S1P1 y S1P5, evitando así la salida de linfocitos desde los nódulos linfáticos y previniendo procesos inflamatorios en el Sistema Nervioso Central que desencadenan una desmielinización. Existe amplio conocimiento científico respecto a que la administración del medicamento a pacientes va a depender de sus características farmacogenéticas, por lo que la FDA recomienda fuertemente realizar un estudio de genotipificación de la enzima que metaboliza siponimod, CYP2C9, cuyas variantes genéticas *2 y *3 clasifican a pacientes como metabolizadores pobres, extensivos o rápidos. Para pacientes homocigotos de CYP2C9*3 siponimod está totalmente contraindicado. Adicionalmente, antes de su prescripción se debe realizar un electrocardiograma, evaluaciones del estado de anticuerpos, oftálmica, estado de vacunación contra varicela y recuento de linfocitos periféricos, ya que el efecto del medicamento es dependiente de la dosis administrada, por lo que se realiza un proceso de titulación en dosis desde los 0,25mg hasta los 2 mg. El protocolo farmacoterapéutico de siponimod es reflejo fidedigno de la utilidad de la farmacogenética en la medicina personalizada..

Siponimod is a selective immunosuppressive medication, developed as the first oral therapy for active secondary progressive multiple sclerosis. This medication acts by modulating the sphingosine 1 phosphate (S1P) receptor, as an antagonist of S1P1 and S1P5, thus preventing the egress of lymphocytes from lymph nodes and preventing inflammatory processes in the Central Nervous System that trigger demyelination. There is extensive scientific knowledge regarding the administration of the medication to patients, which will depend on their pharmacogenetic characteristics. Therefore, the FDA strongly recommends conducting a genotyping study of the enzyme that metabolizes siponimod, CYP2C9, whose genetic variants *2 and *3 classify patients as poor, extensive, or rapid metabolizers. Siponimod is completely contraindicated for patients who are homozygous for CYP2C9*3. Additionally, before prescribing it, an electrocardiogram, assessments of antibody status, ophthalmic evaluation, varicella vaccination status, and peripheral lymphocyte count should be conducted, as the medication's effect is dose-dependent. Therefore, a titration process is carried out starting from 0.25mg up to 2 mg. The pharmacotherapeutic protocol of siponimod is a reliable reflection of the utility of pharmacogenetics in personalized medicine.

[Siponimod (BAF312): General Characteristics and Clinical Implications of Pharmacogenomic Dosage in the Treatment of Active Secondary Progressive Multiple Sclerosis]. / Siponimod (BAF312): Características generales e implicancias clínicas de la dosificación farmacogenómica en el tratamiento de la Esclerosis Múltiple secundaria progresiva.

Siponimod is a selective immunosuppressive medication, developed as the first oral therapy for active secondary progressive multiple sclerosis. This medication acts by modulating the sphingosine 1 phosphate (S1P) receptor, as an antagonist of S1P1 and S1P5, thus preventing the egress of lymphocytes from lymph nodes and preventing inflammatory processes in the Central Nervous System that trigger demyelination. There is extensive scientific knowledge regarding the administration of the medication to patients, which will depend on their pharmacogenetic characteristics. Therefore, the FDA strongly recommends conducting a genotyping study of the enzyme that metabolizes siponimod, CYP2C9, whose genetic variants *2 and *3 classify patients as poor, extensive, or rapid metabolizers. Siponimod is completely contraindicated for patients who are homozygous for CYP2C9*3. Additionally, before prescribing it, an electrocardiogram, assessments of antibody status, ophthalmic evaluation, varicella vaccination status, and peripheral lymphocyte count should be conducted, as the medication's effect is dose-dependent. Therefore, a titration process is carried out starting from 0.25mg up to 2 mg. The pharmacotherapeutic protocol of siponimod is a reliable reflection of the utility of pharmacogenetics in personalized medicine.