Article information
Abstract
Introduction
Natalizumab is a monoclonal antibody that inhibits leukocyte migration across the blood-brain barrier and has been approved for the treatment of relapsing-remitting multiple sclerosis.
ObjectiveTo provide a review and update of the pharmacological and therapeutic characteristics of natalizumab, with special emphasis on the most recently published data on the efficacy, effectiveness and safety of this drug.
DevelopmentSeveral randomized clinical trials in patients with relapsing forms of multiple sclerosis have demonstrated that natalizumab substantially reduces clinical and radiological disease activity. Post hoc analysis of phase III clinical trials and the results of post-approval observational studies indicate that natalizumab significantly increases the proportion of patients with complete clinical and radiological response and is effective in patients with highly active forms of multiple sclerosis and suboptimal response to other treatments. Like other monoclonal antibodies, natalizumab can cause hypersensitivity reactions, which are severe in 1% of patients. Other adverse effects are generally mild or infrequent. Nevertheless, several cases of progressive multifocal leukoencephalopathy have been detected in patients treated with natalizumab monotherapy. The risk of this severe complication seems to increase with the number of doses administered.
ConclusionNatalizumab has a favourable risk-benefit ratio in the treatment of relapsing-remitting multiple sclerosis. However, because of the potential risk of progressive multifocal leukoencephalopathy, patients must be carefully selected and specific protocols must be followed during the drug's administration.
Keywords:
Multiple sclerosis
Natalizumab
Monoclonal antibody
Clinical trial
Progressive multifocal leukoencephalopathy
Resumen
Introducción
Natalizumab es un anticuerpo monoclonal inhibidor de la migración leucocitaria a través de la barrera hematoencefálica, autorizado para el tratamiento de la esclerosis múltiple remitente-recurrente.
ObjetivoRealizar una revisión y actualización de los aspectos farmacológicos y terapéuticos de natalizumab, con especial énfasis en los datos de eficacia, efectividad y seguridad publicados más recientemente.
DesarrolloVarios ensayos clínicos aleatorizados en pacientes con formas recurrentes de esclerosis múltiple han demostrado que natalizumab reduce considerablemente la actividad clínica y radiológica de la enfermedad. El análisis post hoc de ensayos clínicos fase III y los resultados de estudios observacionales postautorización indican que natalizumab incrementa significativamente la proporción de pacientes con respuesta clínica y radiológica completa, y que es eficaz en aquellos con formas muy activas de esclerosis múltiple y con respuesta subóptima a otras terapias. Al igual que otros anticuerpos monoclonales, natalizumab puede causar reacciones de hipersensibilidad, siendo graves en el 1% de los pacientes. Otros efectos adversos de natalizumab son en general leves o poco frecuentes. No obstante, se han detectado varios casos de leucoencefalopatía multifocal progresiva en pacientes tratados con natalizumab en monoterapia. El riesgo de esta grave complicación parece incrementarse con el número de dosis recibidas.
ConclusiónNatalizumab ha demostrado una relación beneficio-riesgo favorable en el tratamiento de la esclerosis múltiple remitente-recurrente. El riesgo potencial de leucoencefalopatía multifocal progresiva, sin embargo, obliga a la selección cuidadosa de los pacientes y a seguir protocolos de actuación específicos durante su administración.
Palabras clave:
Esclerosis múltiple
Natalizumab
Anticuerpo monoclonal
Ensayo clínico
Leucoencefalopatía multifocal progresiva
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