Immunosuppressant therapies in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease of the central nervous
system. Given that MS currently remains incurable and the immunomodulatory therapies do not completely
prevent disease progression in most patients, the final option for managing patients who do not respond
to immunomodulatory treatment is to use a chemotherapeutic agent. Azathioprine, methotrexate,
cyclosporine, mycophenolate mofetil, mitoxantrone, cyclophosphamide and rituximab are the most
utilized agents. Mitoxantrone is currently the only chemotherapeutic agent approved for the treatment of
worsening relapsing-remitting, secondary progressive and progressive relapsing MS. It decreases relapse
rate and progression of disability, and reduces the appearance of new T2 and Gd-enhancing lesions on
MRI. Patients with rapidly worsening, treatment-refractory, relapsing-remitting MS might benefit from
treatment with intravenous cyclophosphamide. The safety profile of azathioprine appears to be more
favorable than the profiles of mitoxantrone or cyclophosphamide but it is not used in rapidly worsening MS.
Azathioprine reduces relapses and disease progression during the first 2-3 years, but is reserved for patients
with progressive course that cannot tolerate other more potent immunosuppressants or as maintenance
treatment after mitoxantrone, because of safety concerns. Mycophenolate Mofetil can improve or stabilize
MS patients as an alternative therapy, either in combination with interferon beta or as monotherapy.Autologous haematopoietic stem cell transplantation could be regarded as a salvage treatment of choice
in “malignant” or treatment-refractory, rapidly deteriorating MS and might lead to prolonged periods of
stable disease. Although immunosuppressants are an important resource in the treatment of MS, their use
is limited by toxicity and potential long-term risk.