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MITOXANTRONA: ¿CUAL ES EL FUTURO? NUEVOS AGENTES INMUNOSUPRESORES POTENCIALES PARA TRATAR LA ESCLEROSIS MULTIPLE

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La información disponible actualmente permite afirmar que la mitoxantrona es eficaz y relativamente segura para controlar la esclerosis múltiple de rápida evolución y la progresión de la discapacidad con la cual se asocia; además, una variedad de fármacos inmunosupresores (previamente empleados con otras indicaciones o creados recientemente) pueden constituir alternativas terapéuticas promisorias.
Autor:
Richard e Gonsette
Columnista Experto de SIIC
Artículos publicados por Richard e Gonsette
Recepción del artículo
2 de Octubre, 2006 		Aprobación
9 de Noviembre, 2006
Primera edición
4 de Mayo, 2007 		Segunda edición, ampliada y corregida
7 de Junio, 2021

MITOXANTRONA: ¿CUAL ES EL FUTURO? NUEVOS AGENTES INMUNOSUPRESORES POTENCIALES PARA TRATAR LA ESCLEROSIS MULTIPLE

Resumen
Desde que la mitoxantrona fuera autorizada para tratar la esclerosis múltiple de rápida evolución, se ha adquirido una cantidad notable de conocimientos acerca de sus mecanismos de acción, su eficacia y su toxicidad a largo plazo. Por otra parte, observaciones recientes sugieren firmemente que la administración temprana de fármacos inmunosupresores como la mitoxantrona y el alemtuzumab es concluyentemente más eficaz que la de interferón beta y acetato de glatiramer para retrasar la aparición de discapacidad irreversible. Por consiguiente, la posible eficacia de agentes inmunosupresores novedosos, usados en otras enfermedades autoinmunes, el trasplante de órganos y la terapia del cáncer para tratar la esclerosis múltiple, ha recibido atención creciente. Esos agentes incluyen anticuerpos monoclonales dirigidos contra células B, linfocitos, monocitos, receptores de interleuquina-2 (IL-2) e integrina alfa 4, así como moléculas originales (pixantrona, derivados del isoxazol) y una nueva generación de fármacos inmunosupresores (fingolimod), con acción sobre el receptor para esfingosina-1-fosfato, el cual modula la recirculación linfocitaria. Además, se han actualizado los beneficios de inmunosupresores previamente usados como tratamiento no autorizado para la esclerosis múltiple, tales como la ciclofosfamida y la cladribina. Esta revisión considera la información más reciente acerca de la eficacia y la seguridad de la mitoxantrona y de las nuevas terapias experimentales, actualmente en evolución.

Palabras clave
fingolimod, esclerosis múltiple, inmunosupresión, mitoxantrona, natalizumab


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Mitoxantrone: What Comes Next? New Potential Immunosuppressants in Multiple Sclerosis

Abstract
Since the approval of mitoxantrone for the treatment of aggressive multiple sclerosis, an interesting amount has been learned about its mechanisms of action, its efficacy and its long-term toxicities. On the other hand, recent observations strongly suggest that early administration of potent immunosuppressants such as mitoxantrone and alemtuzumab are definitely more efficacious than interferons beta and copaxone to delay the development of irreversible disability. The potential efficacy in multiple sclerosis of recent immunosuppressants used in other autoimmune diseases, organ transplantation and cancer therapy has thus received increasing attention. Those agents encompass monoclonal antibodies targeting B cells, lymphocytes and monocytes, IL2 receptor, a4 integrin as well as new molecules (pixantrone, isoxazole derivatives) and a new generation immunosuppressants (fingolimod) targeting the sphingosine 1-phosphate 1 receptor which modulates lymphocyte re-circulation. In addition, the benefit of immunosuppressants previously used as off-label treatments of multiple sclerosis such as cyclophosphamide and cladribine has been revisited. This review addresses the most recent data concerning the efficacy and safety of mitoxantrone and those new experimental therapies currently in progress.

Key words
multiple sclerosis, immunosuppression, mitoxantrone, natalizumab, fingolimod


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Especialidades
Principal: Neurología
Relacionadas: Farmacología, Inmunología, Medicina Farmacéutica, Medicina Interna



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Richard E Gonsette, National Center for Multiple Sclerosis, 1820, Vanheylenstraat 16, B, Melsbroek, Bélgica
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