IMMUNOSUPPRESSION WITH AZATHIOPRINE, PREDNISONE, AND CYCLOPHOSPHAMIDE1
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An immunosuppressive regimen consisting of azathioprine (AZ), prednisone, and intermittent i.v. infusions of 400 mg of cyclophosphamide (CY) in the first post-transplant month was prospectively compared with a no CY regimen. There were no significant differences in patient or graft survival, graft function, or infectious complications between the two regimens.Keywords:
Immunosuppression
Regimen
The current immunosuppressive treatment of patients with autoimmune hepatitis consists of prednisone and azathioprine. High doses of prednisone used to obtain the remission of the disease are associated with serious adverse effects. To avoid harmful consequences of prednisone, we proposed to treat patients with oral cyclosporine to obtain the remission of the inflammatory process.This case and review of the cases in the literature show that cyclosporine can induce remission of liver disease in children with autoimmune hepatitis, with few and well tolerated adverse effects.
Autoimmune Hepatitis
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To analyse the histological evolution of endomyocardial biopsies from children with active myocarditis, submitted or not to immunosuppressive therapy.Four groups of patients were compared, clinically treated as follows: group I--anticongestive drugs (4 patients); group II--prednisone (5 patients); group III--prednisone plus azathioprine (9 patients); group IV--prednisone and cyclosporine (5 patients).No patient from group I presented any histological improvement during a mean period of 9 months, while evident histological improvement occurred in 25% of patients from group I, 67% from group III and 80% from group IV. The microscopical aspect of resolving myocarditis was only observed in patients from groups III and IV, after treatment.The immunosuppressive therapy with azathioprine or cyclosporine plus prednisone leads to decrease of active myocarditis intensity in a higher proportion of cases than the treatment with only prednisone or no immunosuppressive drugs.
Dilated Cardiomyopathy
Endomyocardial Biopsy
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The influence of high-dose prednisone and azathioprine therapy on oligoclonal IgG in the CSF of MS patients was studied. The oligoclonal bands were present in 93% of patients treated with prednisone and in 90% of patients treated with azathioprine. After the treatment with prednisone, the oligoclonal bands density was diminished in 3 patients, and after the treatment with azathioprine in 1 patient. The number of bands and their pattern remained the same.
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Abstract. Ten consecutive patients with oliguric extracapillary glomerulonephritis have been treated with prednisone and/or azathioprine. Six patients responded favourably to the treatment, while 4 died of uraemia. Of the 6 responders 5 were treated with prednisone and azathioprine and one with prednisone. The 6 patients are still on immunosuppressive treatment and have creatinine clearances of 21–75 tnl/min 2–43 months after start of treatment. Thus treatment with prednisone and azathioprine seems to improve the prognosis of oliguric extracapillary glomerulonephritis.
Rapidly progressive glomerulonephritis
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Twenty-five patients taking part in a controlled trial to compare azathioprine plus prednisone with prednisone alone in the treatment of pemphigoid were followed up for three years. Results showed that the addition of azathioprine 2.5 mg/kg body weight daily reduced the total maintenance dose of prednisone needed by about 45%, with no increase in serious side effects or mortality. The suggestion that azathioprine might increase the risk of disseminated malignancy in elderly patients was not supported. We conclude that in future trials the combination of azathioprine with prednisone should be used as the standard treatment for comparison.
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Immunosuppression
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Immunosuppressive drug
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50 patients with proliferative glomerulonephritis due to lupus erythematosus were assigned in order of their chronologic appearance at the hospital alternately to treatment with either daily high dose prednisone, azathioprine, prednisone and azathioprine combined, or combined azathioprine and heparin. Prednisone alone was ineffective both from a standpoint of maintaining kidney function or from preserving a state of well being. Only 2 of 15 patients treated with prednisone are doing well with an average survival for the group of 19 months. Azathioprine, alone, appeared very effective with 9 of 13 patients alive and doing well with an average survival of 38 months. Combinations of either azathioprine and prednisone or azathioprine and heparin were most successful, only 2 of 13 in each group died of renal failure. Complications of prednisone administra'ion were high both when prednisone was given alone or in combination with azathioprine.
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Abstract From January 1983 to October 1990, 41 patients with generalised myasthenia gravis were randomly given either prednisone or azathioprine. The main goal was to record the time to the occurrence of the first episode of deterioration. During a mean follow-up of 30 months, 21 patients showed deterioration, 12 in the prednisone group and nine in the azathioprine group (p = 0.40). No difference was observed between the two groups in muscular score and functional grade, assessed at the end of each treatment year, or in tolerance. Treatment failure occurred in 17 patients, 12 in the prednisone group and five in the azathioprine group (p = 0.02); even after adjustment for imbalances in prognostic features, the failure rate remained 2.8 times higher in the prednisone group than in the azathioprine group (p = 0.5). In the patients in whom treatment failed, symptoms were initially more severe than in the others, but the combination of prednisone and azathioprine resulted in clinical improvement, consisting of remission or only minor deficits in half of the patients after two years of treatment. These findings indicate that azathioprine increases treatment response compared with prednisone, although no difference in the duration of improvement was demonstrated. Nevertheless, it appears that the most severe forms of the disease, often resistant to prednisone or azathioprine alone, could benefit from the combination of both drugs.
Interim analysis
Interim
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