Cyclophosphamide (Cytoxan) is an ImmunoSuppressive drug that is usually given to treat Cancer. Its use in the treatment of MS stems from evidence that MS is an AutoImmune process directed against the Central Nervous System.
An ImmunoSuppressive drug would therefore be expected to slow down or stop the DeMyelinating process without, however, being able to reverse damage or improve symptoms.
In 1983, the report of a 4 year study of Cyclophosphamide for the treatment of Chronic/Progressive MS was published in the New England Journal of Medicine. This study demonstrated stabilization of the disease process in about 80% of the patients for periods of up to one year, compared to stabilization in 20% of patients who received only ACTH.
A subsequent study of 44 patients with Chronic/Progressive MS who were treated with either Cyclophosphamide or a placebo, failed to show any benefit in the treated group. Other studies have either confirmed a beneficial effect of Cyclophosphamide, or have failed to show benefit from this treatment.
At least one study has shown continued stabilization of disease with 'booster' doses of Cyclophosphamide given every other month. The results of a multicenter trial in Canada indicated that patients who received either IntraVenous or Oral Cyclophosphamide combined with Prednisone did no better than a similar group of patients who received placebo.
In this study the placebo response was 75%. The Side-Effects of Cyclophosphamide treatment include Nausea, Vomiting, and Bladder Cancer. The use and efficacy of Cyclophosphamide as a treatment for MS remains experimental and controversial.
Long-Term side effects include Sterility, Mutations, and the Increased Risk of Cancer.
Cyclosporine (Sandimmune) is a powerful ImmunoSuppressive drug that first came to attention when it was shown to significantly reduce rejection rates in organ transplantation. Unlike most ImmunoSuppressive drugs, it appears to have a specific action against primarily one type of white blood cell, the Helper T-Cells.
Since there is some evidence that these cells are abnormally active during acute exacerbations of MS, and since it has been shown to be effective in treating other AutoImmune Diseases and EAE (the animal model of MS), Cyclosporine was tried in a multicenter double blind, placebo controlled trial, in patients with Progressive MS.
The study enrolled almost 600 men and women and followed them for two years. Half received Cyclosporine, and half received placebo, with neither the doctors nor the patients being aware of the type of treatment.
Many variables were studied, such as clinical status, functional abilities, blood, spinal fluid, and MRI parameters. Those patients who received Cyclosporine had a slightly (but statistically significant) slower rate of disease progression than the placebo group.
There were no differences in activities of daily living, and no change in MRI or spinal fluid parameters. Additionally, there were serious Side-Effects associated with Cyclosporine use, namely Kidney Damage and High Blood Pressure.
Another study done in Germany compared Cyclosporine to another ImmunoSuppressive agent, Azathioprine. Over 80 patients in each treatment group completed a two year double blind protocol. No significant differences between the two groups were apparent at the end of the study.
The Cyclosporine group had twice as many Side-Effects as the Azathioprine-treated patients. It has been concluded therefore, that the benefit vs. risk of Cyclosporine administration for the treatment of MS did not justify its use under most circumstances.
Methotrexate is an effective and safe treatment for Rheumatoid Arthritis, a disease with similarities to MS, findings presented at the May 1994 meetings of the American Academy of Neurology indicate that Methotrexate may delay progression of impairment, especially in the upper extremities, in certain individuals with Primary/Progressive MS.
For people with Progressive MS and moderate disability, weekly low-dose oral Methotrexate may safely help to delay progression of impairment. Upper extremity function seems to be most affected by the medication, while lower extremity function - including ambulation - is not affected.
Methotrexate is a well known, widely available and affordable chemotherapy agent that has been used successfully for years in the treatment of certain Leukemias, Lymphomas and other Cancers, as well as in Rheumatoid Arthritis.
In spite of the potential for toxicity, Methotrexate has been safely used in these conditions for many years. The mechanism of action of Methotrexate in MS is not clear, but the drug is known to regulate and suppress Immune function and to fight inflammation.
While it is unfortunate that disability relating to ambulation did not seem to benefit from this treatment, the study did indicate that treatment could help preserve upper-extremity functions for a longer period of time, which has important consequences for activities of daily living and for mobility.
The Medical Advisory Board of the National Multiple Sclerosis Society considers the benefit from Methotrexate to be limited only to those with moderate disability and a Progressive course of disease.
Larger studies of Methotrexate for MS are warranted. Individuals who are concerned about the use of Methotrexate to treat MS should consult their personal physicians.