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

Abstract

The aim of this trial was to compare the efficacy and tolerance of cyclosporine A (CYA) and azathioprine (AZA) as long-term immunosuppressive treatment for patients with multiple sclerosis. 31 randomly assigned patients completed a 12-month treatment with either CYA (5 mg/kg/day) or AZA (2 mg/kg/day). Evaluation included serial quantitative clinical assessments and circulating T cell markers. The CYA treatment group improved in only one of three scoring systems (p < 0.05), while no difference was observed in the AZA group. CYA and AZA did not influence CD4+/CD8+ ratio of circulating T cells but affected HNK-1+ cells. The overall frequency of abnormal laboratory values were comparable in both groups. We conclude that CYA given in a low dose is relatively well tolerated but its benefits appear to be of limited value.

Hyperactivation of nuclear factor of activated T cells 1 (NFAT1) in T cells attenuates severity of murine autoimmune encephalomyelitis

“…NFAT1, thus, acts as a gatekeeper for multiple divergent pathways downstream of T-cell activation (Th1/Th2/ Th17/Treg)-the AVT trangenics illustrate its role as a calibrator for graded TCR signals, excessive activation resulting in immunomodulation rather than exacerbation of autoimmunity. Regardless of mechanism, our results indicate that augmentation of NFATdependent transcription might be therapeutic in at least some cases of autoimmune disease and may explain the limited efficacy of CsA and other calcineurin inhibitors in autoimmunity in the clinic (44).…”

Systematic review of immunomodulatory drugs for the treatment of people with multiple sclerosis: Is there good quality evidence on effectiveness and cost?

“…The NNTs to prevent relapse at 1 year were calculated as 10 and 7 (95%CI 3-infinity) respectively. The third study (score 2/5)6 did not report on relapse rate.…”

“…The quantity and quality of studies varied between the different immunomodulatory drugs. Evidence on the effectiveness of azathioprine came from a good quality systematic review4 and two subsequent RCTs: one good quality placebo controlled double blind trial5 and one poor open label RCT 6. Of the five RCTs assessing cyclophosphamide,7-11 only one was a good quality double blind crossover RCT 8.…”

Azathioprine and methotrexate in multiple sclerosis

“…The first of these trials, published in 1990 [25], was an open, controlled trial, no ITT was used and the intervention was azathioprine (2 mg/kg/day) versus cyclosporine (5 mg/kg/day). The number of patients was 41 (azathioprine 21, cyclosporine 20).…”