I am interested in finding out the latest information on treating multiple sclerosis (MS) patients with cyclophosphamide (Cytoxan). What have been the results of this treatment? What other chemotherapeutic or immunomodulating therapies are being used?
from June Halper, MSN, ANP, FAAN, 01/02/01
Evidence exists that MS is more than a demyelinating disease. MS is the result of inflammation and destruction of myelin, which results in permanent and irreversible axonal damage. This new knowledge about the immunology of multiple sclerosis has led to treatments that suppress the immune system globally and/or selectively modify the immune response.
Cyclophosphamide (Cytoxan) is in a class of immunosuppressant agents that has been used to treat MS since the early 1980s. There have been mixed research data regarding its efficacy; Dr. Howard Weiner's group in Boston, Massachusetts, continues to use this treatment based on their research findings, whereas a recent Canadian study did not support these results. There are current studies examining the efficacy of Cytoxan given in combination with immunomodulating therapies such as interferon beta-1a (Avonex).
In October 2000, the FDA approved an immunosuppressant drug, mitoxantrone (Novantrone), for "worsening" MS. Worsening MS is that type of course in which patients do not fully recover after attacks or continue to worsen between attacks. This is the first immunosuppressant medication that has been approved for multiple sclerosis.
In contrast, immunomodulating agents such as interferon beta-1b (Betaseron), Avonex, and glatiramer acetate (Copaxone) are approved for relapsing forms of the disease. These therapies selectively modify the immune response in hopes of reducing attack frequency and reducing the long-term burden of disease both clinically and on MRI. Interferon beta-1a and -1b are recombinant proteins that are thought to exert their effects by inhibiting inflammation and the migration of white blood cells across the blood-brain barrier. In contrast, glatiramer acetate, a synthetic polypeptide thought to resemble myelin basic protein, may act by stimulating immune suppressor lymphocytes that then release anti-inflammatory cytokines. Glatiramer acetate may also compete with myelin antigens for binding to antigen-presenting cells, thereby preventing autoimmune reactions that lead to demyelination.
Recent studies using interferon beta-1a have demonstrated delay in a second exacerbation, confirming the diagnosis of multiple sclerosis, in patients with a single attack or CIS -- clinically isolated syndrome.
All 3 immunomodulating agents are given by means of self-injection: interferon beta-1a intramuscularly weekly; -1b subcutaneously every other day; glatiramer acetate subcutaneously daily. Interferon therapy requires the patient to have regular blood work (complete blood count and liver enzymes), whereas glatiramer acetate does not.
While the "jury is still out" regarding the efficacy of Cytoxan, mitoxantrone seems to be an important addition in the care of patients with progressive multiple sclerosis. For those patients with relapsing forms of MS, all 3 immunomodulating therapies provide a substantial benefit in relapse reduction, potential modification of disease course, and benefit of protection from the development of MS-related lesions found on magnetic resonance imaging (MRI) scans. Currently, there are 2 important studies examining 2 forms of interferon beta-1a (Avonex and Rebif) for efficacy in relapsing MS and an oral form of Copaxone in this type of MS as well.
The message for those
caring for patients with multiple sclerosis is that there is hope for patients
who are treated early. There are now treatment choices where a decade ago
there were none. For healthcare providers, patient and family education
provide opportunities to promote adherence to these important new protocols.
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