Long-term Prescription of Azathioprine in Multiple Sclerosis. A Review of Published Series

Abstract

The interest of Neurologists for the utilisation of continuous immunosuppression during many years in the treatment of Multiple Sclerosis arouse even before Azathioprine was available. Around 1968 Azathioprine became the major prescription in this field. It was supported by the clinical observation of severe cases, with frequent attacks and uninterrupted progress of the physical disability, who under treatment were apparently stabilized for years with no further worsening of their neurological status. Such results were collected in a few centers and seemed to deserve further studies. Randomized double blind studies have been achieved during the period 1978–1982; but they failed to show clear differences between the treated patients and the control untreated group. The question then had to be considered: were the first clinical observations a false evaluation through multiple biases, as it occurs too easily with open, non formalized trials ? or was there some limitation in the randomized double-blind procedures? This questioning is justified on two important points. 1) The double-blind studies are of relatively short duration, one or two years, much shorter than the pilot studies. 2) The cases entered in the double-blind series look relatively mild if compared to those selected for the open trials. For instance the control cases did not deteriorate during the period of the study or did so very moderately (one step in the scale)some of them even improving their score.