The Use of Ciclosporin (CyA) in Multiple Sclerosis — Trial Design and Tolerance

Abstract

Although the aetiology of multiple sclerosis is unknown, there is a considerable body of evidence suggesting that immunological function is abnormal. For example, the cerebrospinal fluid contains abnormal immunoglobulins with evidence that they are produced within the central nervous system compartment, raised titres of various viral antibodies, especially measles, are found in the serum and there is evidence that T cell subsets are abnormal particularly in relation to relapses of the condition. While there is no adequate animal model of multiple sclerosis, experimental allergic encephalomyelitis (EAE) does to some extent mimic multiple sclerosis particularly in those models that have a relapsing and remitting course. There is no doubt that EAE is an immunological disease and certain of the abnormalities seen in it parallel those found in multiple sclerosis. As immunosuppression is an effective prophylactic therapy for EAE and the use of ciclosporin has been shown to be of value even if given after the first clinical signs have developed [1], it was logical to try giving CyA to patients with multiple sclerosis. In 1979 a pilot study in which 5 patients were given CyA at a dose of 10 mg/per kg/day for a short period showed that there were no adverse effects upon the course of the disease and certainly none of the patients deteriorated. For this reason it was decided to set up a small double-blind controlled study of CyA in multiple sclerosis.