Dataset Information

Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium in De Novo Kidney Transplantation.

ABSTRACT: The increased tolerability of enteric-coated mycophenolate sodium (EC-MPS), compared to mycophenolate mofetil, among kidney transplant recipients has the potential to facilitate cyclosporine (CsA) minimization. Therefore, a prospective trial to determine the optimum EC-MPS dose in CsA-based immunosuppression regimens is necessary.A comparative, parallel, randomized, open-label study was performed for 140 patients from four centers to compare the efficacy and tolerability of low dose CsA with standard dose EC-MPS (the investigational group) versus standard dose CsA with low dose EC-MPS (the control group) for six months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure [biopsy-confirmed acute rejection (BCAR), death, graft loss, loss to follow-up], and adverse events were compared.The mean estimated glomerular filtration rate (eGFR) of the investigational group at six months post-transplantation was non-inferior to that of the control group (confidence interval between 57.3 mL/min/1.73m² and 67.4 mL/min/1.73 m², p<0.001). One graft loss was reported in the control group, and no patient deaths were reported in either group. The incidence of BCAR of the investigational group was 8.7%, compared to 18.8% in the control group (p=0.137), during the study period. There were no significant differences (p>0.05) in the incidence of discontinuations and serious adverse events (SAE) between the groups.CsA minimization using a standard dose of EC-MPS kept the incidence of acute rejection and additional risks as low as conventional immunosuppression and provided therapeutic equivalence in terms of renal graft function and safety issues.

SUBMITTER: Lee SH

PROVIDER: S-EPMC5122640 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium in De Novo Kidney Transplantation.

Lee Su Hyung SH Park Jae Berm JB Oh Chang Kwon CK Kim Myoung Soo MS Kim Sung Joo SJ Ha Jongwon J

Yonsei medical journal 20170101 1

<h4>Purpose</h4>The increased tolerability of enteric-coated mycophenolate sodium (EC-MPS), compared to mycophenolate mofetil, among kidney transplant recipients has the potential to facilitate cyclosporine (CsA) minimization. Therefore, a prospective trial to determine the optimum EC-MPS dose in CsA-based immunosuppression regimens is necessary.<h4>Materials and methods</h4>A comparative, parallel, randomized, open-label study was performed for 140 patients from four centers to compare the effi ...[more]

PMID: 27873516

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Project description:BACKGROUND:The use of mycophenolate mofetil (MMF) in autoimmune disease is often limited by adverse effects. In this single-centre, open label, parallel design study, we investigated whether enteric-coated mycophenolate sodium (MS) is better tolerated and therefore more efficacious than MMF in primary systemic vasculitis (PSV) and systemic lupus erythematosus (SLE). METHODS:Forty patients with vasculitis or systemic lupus erythematosus (SLE) due to commence MMF for active disease or remission maintenance were randomized to receive either 1440 mg/day MS or 2000 mg/day MMF (18 PSV, 2 SLE per group) in addition to corticosteroids. Random allocation was performed by minimization for age, diagnosis and renal function using a computer algorithm. Twenty-five were treated for active disease (5 first-line therapy, 20 salvage therapy) and 15 for remission maintenance. The composite primary end point was treatment failure and/or drug intolerance over 12 months. Treatment failure was defined as failure to achieve remission by 6 months or disease relapse and treatment intolerance was defined as inability to tolerate and maintain the target dose of MS or MMF within 12 months. RESULTS:Forty patients were included in the analyses. MS was associated with a lower primary end point rate [hazard ratio (HR) 0.37; 95% CI 0.17-0.80; P = 0.012] (11/20, 55% patients) compared with MMF (17/20, 85% patients). Treatment failure alone was less common in the MS group (HR 0.28; 95% CI 0.095-0.82; P = 0.020), although drug intolerance did not differ between groups (HR 0.53; 95% CI 0.20-1.42; P = 0.21). Despite randomization, patients in the MMF group may have had a higher baseline risk for treatment failure; more MMF patients had refractory disease and granulomatosis with polyangiitis (Wegener's). A glomerular filtration rate (GFR) ?40 mL/min was associated with intolerance. Serious adverse events were common (55% MMF and 45% MS patients). CONCLUSIONS:No differences in treatment tolerance were observed between the MS and MMF groups. Despite similar treatment intolerance, MS was associated with improved efficacy in PSV and SLE compared with MMF. However, baseline group imbalances in factors potentially affecting remission and relapse may have influenced the results. Treatment intolerance was common and strongly associated with low GFR. Further treatment trials are warranted to investigate the effect of GFR on mycophenolic acid pharmacokinetics and clinical outcomes (ISRCTN83027184; EUDRACT 2005-002207-16; Funding Novartis UK).

Project description:Background: Despite significant improvements in short-term kidney transplant survival, comparable increases in 5 and 10-year outcomes have not been achieved. Chronic allograft nephropathy (CAN) is a major cause of late graft loss. Toxic nephropathy and inadequate long-term immunosuppression are possible factors. We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure, and gene expression. Methods: Sixty-one kidney recipients received mycophenolate mofetil (MMF), and prednisone (P). Randomized patients received concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Findings: Comparing sirolimus/MMF/P to cyclosporine/MMF/P at two years, there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dl; p=0.008), significantly higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 cc/min; p=0.008), iothalamate GFR (60.6 vs. 49.2 cc/min; p= 0.018), and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p=0.013). Regression analysis of calculated GFR’s from 1 to 36 months yielded a positive slope for sirolimus of 3.36 ml/min/year, and a negative slope for cyclosporine of –1.58 ml/min/year (p=0.008). Gene expression profiles of kidney biopsies with higher Banff CAN scores confirmed significant up regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. Interpretation: At two years the sirolimus-treated patients have better renal transplant function, a diminished prevalence of CAN, and down regulated expression of genes responsible for the progression of CAN. All may provide for an alternative natural history with improved graft survival. Keywords = Cyclosporine Keywords = Sirolimus Keywords = Transplantation Keywords = DNA microarrays Keywords = calcineurin inhibitors Keywords: parallel sample. This dataset is part of the TransQST collection.

Dataset Information

Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium in De Novo Kidney Transplantation.

Publications

Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium in De Novo Kidney Transplantation.

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