Cyclosporine and multiple sclerosis: the cons

Although the pathophysiologic cause of multiple sclerosis (MS) is unknown, there is a considerable body of evidence that immunologic factors play a part. As experimental allergic encephalomyelitis (EAE), particularly its relapsing and remitting forms, has some similarities to MS, and because EAE can be modified by immunosuppression, a large number of immunomodulating drugs have been given to patients with MS. None of these therapies has been dramatically successful, but immunosuppression with azathioprine, mercaptopurine, and cyclophosphamide have been of marginal benefit to the patients. The reason for this relative failure of such therapy in MS might be because these conventional immunosuppressants do not sufficiently modify the immunologic abnormalities in the patients. Cyclosporine A is the first of a new generation of immunosuppressants that appear to be more potent, at least in the field of transplantation. For this reason, it is logical to determine its efficacy in MS. Based on the hypothesis that MS is an immunopathologic disease, many immunosuppressive therapies have been tried for this condition. Cyclosporine is the newest such agent. Studies in animals with EAE indicate that the drug suppresses the disease, but when the drug is stopped the disease exacerbates. This may also happen in MS. Furthermore, our studies indicate that cyclosporine has a low therapeutic index, so that in doses that are well tolerated the drug is not effective and in doses that are effective there is significant toxicity. For these reasons, we reluctantly conclude that cyclosporine should not be used in MS.