Clinical efficacy of cyclosporin a neoral in the treatment of paediatric lupus nephritis with heavy proteinuria

Abstract

Cyclosporin A (CsA) was introduced in recent years for the treatment of lupus nephritis in patients with steroid resistance or in those with severe corticosteroid toxicity. Our previous study on paediatric patients showed that Neoral (a new microemulsion formulation) had better bioavailability than CsA capsules. To evaluate the clinical efficacy of Neoral in children with lupus nephritis compared with conventional therapy, we performed an open randomized study on 40 children, ranging from 9 to 14 yr old, with class III-V lupus nephritis and heavy proteinuria. They were randomly assigned to either Neoral (5 mg/kg/day), administered q.12.h, or prednisolone (2 mg/kg/day) plus cyclophosphamide (2 mg/kg/day) for 1 yr. Both groups showed a significant decrease in proteinuria (Neoral: 4.62 +/- 1.93 to 0.35 +/- 0.29 g/day, P < 0.05; prednisolone plus cyclophosphamide: 4.52 +/- 1.86 to 0.62 +/- 0.21 g/day, P < 0.01). The CH50 haemolytic assay titre decreased after 1 yr of Neoral treatment (26.5 +/- 0.9 to 21.4 +/- 2.2 U/ml, P < 0.05). Serum C3 and anti-double-stranded (ds) DNA antibody levels also fell with Neoral (C3: 86.2 +/- 6.8 to 76.3 +/- 4.5 mg/dl; anti-ds DNA antibodies: 14.1 +/- 3.2 to 8.2 +/- 1.4 IU/ml, P < 0.05). The Neoral group had a significant increase in growth rate over the prednisolone plus cyclophosphamide group (8.2 +/- 1.1 cm/yr vs 2.7 +/- 0.6 cm/yr, P < 0.01) with improvement of growth status. During the study period, patients tolerated Neoral well with no significant changes in renal function, liver function or lipid profile. Our study implies that Neoral appears to be effective in suppressing proteinuria. Neoral should be regarded as being adjunctive therapy, perhaps with a steroid-sparing effect, in paediatric lupus nephritis. However, its long-term use awaits further studies.

Population Pharmacokinetic Approach to the Use of Low Dose Cyclosporine in Patients with Connective Tissue Diseases

“…Therefore, in this study, it was adopted blood trough concentration of 80-150 ng/mL, as an effective and less toxic from the previous reports. [13][14][15][16][17][18][19] Administration plans for cyclosporine based on the area under the blood concentration-time curve (AUC) for transplantation patients have been extensively investigated and directions for use have been established. In recent years, Nagai et al reported 32) that the AUC was useful for monitoring the clinical and adverse effects of cyclosporine in dermatomyositis-associated progressive interstitial pneumonia patients.…”

“…rine was maintained at 80-150 ng/mL [13][14][15][16][17][18][19] in a steady state was calculated as the ratio of the number of simulated patients to the total number of patients.…”

“…Simulations were performed for cyclosporine doses ranging from 25 to 150 mg (q12h). The probability (%) that the concentration of cyclosporine was maintained at 80-150 ng/mL [13][14][15][16][17][18][19] in a steady state is shown in Table 4.…”

“…12) Recent studies reported low dose cyclosporine therapy, which was adjusted to gain of blood trough concentration approximate 80-150 ng/mL, was an effective and less toxic cyclosporine therapy for the regulation of connective tissue diseases with RA, 13) SLE, [14][15][16] and lupus nephritis. [17][18][19] Population pharmacokinetic methods, with the ability to incorporate covariates from sparse drug concentration data, offer an opportunity to generate a dosing regimen. Although a dosing method that takes into account the various factors that influence the pharmacokinetics of cyclosporine is needed, pharmacokinetic studies on cyclosporine in collagen disease patients are limited, as are population pharmacokinetic studies.…”

Lupus Nephritis

“…In an open randomized trial, 40 children with class III-V LN received either CSA or a combination of oral cyclophosphamide with corticosteroids for 1 year (26). Both groups showed equivalent efficacy in terms of reduction in proteinuria and autoantibody levels with preservation of renal function.…”