Cyclosporine versus azathioprine in the long‐term treatment of multiple sclerosis—results of the german multicenter study

Abstract

In a double-blind controlled trial of 194 patients with clinically definite active multiple sclerosis, 98 were randomized to treatment with cyclosporine (CyA, 5 mg/kg/day), and 96 to treatment with azathioprine (Aza, 2.5 mg/kg/day). Eighty-five patients in the CyA group and 82 in the Aza group completed a treatment period of 24 to 32 months in accordance with the study protocol. No significant differences could be detected between the two treatment groups at the end of the trial. Assessment was done by serial quantitative neurological examinations and Kurtzke's Expanded Disability Status Scale. Frequency of relapse and patient self-evaluation also failed to show significant differences. Overall deterioration observed in both groups during the trial was only minor. The incidence of side effects in the CyA group was more than two times that in the Aza group. We conclude that CyA as a single agent cannot be the drug of final choice in long-term immunosuppressive treatment of relapsing-remitting and relapsing-progressive multiple sclerosis.

Cyclosporine versus Azathioprine in the Treatment of Multiple Sclerosis: 12-Month Clinical and Immunological Evaluation

“…The reasons for that are not known, but one may wonder whether the concentration of CYA in the brain is sufficient to induce a local immu nosuppression [19], Because of its rather narrow risk/ therapeutic ratio, due to its clearly dose-dependent neph rotoxicity [20], we feel that long-term administration of larger doses of CYA would be unsafe. Indeed, the ab sence of significant nephrotoxicity in this study, as well as in another recently reported large multicenter study [21 ], can probably be due to the relatively low dosage of CYA used.…”

“…Although in this study CYA appears to have some potential efficacy, a recently completed cooperative trial comparing AZA and CYA showed no advantage in favor of CYA [21]. Another study [22] reported a beneficial effect of CYA upon the progression of the disease, relapse rate and relapse severity but only with a higher dosage of 7.2 mg/kg/day.…”

Imaging of multiple sclerosis: Role in neurotherapeutics

“…Historically, T2 BOD was first used as potential supportive outcome in major clinical trials of cyclosporine versus azathioprine in Europe, and versus placebo in North America. [42][43][44][45] Both studies failed to show clinical benefit, and both documented progression of MRI-monitored pathology that was unaffected by treatment. Several years later, the first study used attenuated change in T2 BOD on active treatment with IFNB-1b compared with placebo to supplement the clinical endpoint and support drug approval by the FDA.…”

Consenso expandido do BCTRIMS para o tratamento da esclerose múltipla: I. As evidências para o uso de imunossupressores, plasmaférese e transplante autólogo de células tronco

“…Houve um elevado índice de desistência (44%) 24 . Em 1988, Kappos e col. demonstraram, em estudo comparativo entre ciclosporina e azatioprina, que os resultados de eficácia terapêutica eram semelhantes, contudo com um perfil de efeitos colaterais muito vantajoso para a azatioprina 25 .…”