Postmarketing evaluation of mycophenolate mofetil-based triple therapy immunosuppression compared with a conventional azathioprine-based regimen reveals enhanced efficacy and early pharmacoeconomic benefit after renal transplantation

Wüthrich, Rudolf P.; Weinreich, T; Schwarzkopf, Andreas; Candinas, Daniel; Binswanger, U

doi:10.1016/s0041-1345(98)01355-4

Cited by 6 publications

(3 citation statements)

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“…Conversely, by lowering the rejection rate, substantial savings in the costs of hospitalization and anti-T-cell therapy can be achieved. A formal pharmacoeconomic analysis is required to evaluate the cost-benefit balance of the use of MMF more thoroughly (17).…”

Section: Discussionmentioning

confidence: 99%

A Controlled Trial Comparing Two Doses of Cyclosporine in Conjunction with Mycophenolate Mofetil and Corticosteroids

Sévaux

Gregoor

Hené³

et al. 2001

Journal of the American Society of Nephrology

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Abstract. It is unknown whether the addition of mycophenolate mofetil (MMF) to cyclosporine (CsA) and prednisone after renal transplantation (RTx) allows for a reduced dose of CsA, to minimize the incidence of CsA-related side effects and to reduce costs. Therefore, 313 renal allograft recipients were randomized for treatment with MMF (1000 mg twice a day), prednisone, and either conventional- or low-dose CsA during the first 3 mo after RTx. The target trough levels were 300 and 150 ng/ml, respectively, during the first 3 mo and 150 ng/ml in both groups thereafter. A total of 313 patients were included: 161 patients received a conventional dose and 152 received a low dose of CsA. During the first 6 mo after RTx, graft failure or patient death occurred in 19 of 161 patients (12%) in the conventional-dose group and in 11 of 152 patients (7%) in the low-dose group (not significant). Biopsy-proven acute rejection occurred in 36 of 161 patients (22%) in the conventional-dose group and in 29 of 152 patients (19%) in the low-dose group (not significant). The incidence of delayed graft function was similar in both groups (31 of 161 [19%] versus 28 of 152 [18%]; not significant). Serum creatinine did not differ between the conventional- and the low-dose groups: 151 ± 56 μmol/L versus 142 ± 49 μmol/L at 3 mo and 141 ± 60 μmol/L versus 136 ± 49 μmol/L at 6 mo. There were no differences between the groups regarding BP, lipid metabolism, and infectious complications. In the low-dose group, an estimated $500 per patient was saved on the costs of CsA. In conclusion, the addition of MMF to CsA and prednisone after RTx allows the use of a lower-than-conventional dose of CsA, without increasing the risk of rejection.

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Section: Discussionmentioning

confidence: 99%

A Controlled Trial Comparing Two Doses of Cyclosporine in Conjunction with Mycophenolate Mofetil and Corticosteroids

Sévaux

Gregoor

Hené³

et al. 2001

Journal of the American Society of Nephrology

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“…This advantage typically has been due to decreases in the number of episodes of acute rejection, the resulting cost avoidance, and decreased length of stay in the hospital among MMF-treated patients. [38][39][40][41][42][46][47][48] Mycophenolate has also been compared to everolimus. The economic analysis was based on a multicenter, international trial for prevention of rejection the first year after kidney transplantation.…”

Section: Pharmacoeconomic Analysis Of Maintenance Therapiesmentioning

confidence: 99%

Update on Pharmacoeconomics in Transplantation

Cavanaugh

Martin

2007

Prog Transpl

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“…For instance, PTD is found in heart transplant patients with a progressive worsening on renal function due to cyclosporine (CsA) nephrotoxicity [ 12 ]. In parallel, immunosuppression with mycophenolate mofetil (MYF) is associated with less acute rejection after kidney transplantation [ 13 ], offering a therapeutic alternative for patients with renal dysfunction caused by CsA. However, a large number of transplant patients in developing countries still receive maintenance immunosuppression regimens containing low-cost drugs, including CsA, azathioprine (AZA), and steroids [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Intragraft transcriptional profiling of renal transplant patients with tubular dysfunction reveals mechanisms underlying graft injury and recovery

et al. 2016

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BackgroundProximal tubular dysfunction (PTD) is associated with a decreased long-term graft survival in renal transplant patients and can be detected by the elevation of urinary tubular proteins. This study investigated transcriptional changes in biopsies from renal transplant patients with PTD to disclose molecular mechanisms underlying graft injury and functional recovery.MethodsThirty-three renal transplant patients with high urinary levels of retinol-binding protein, a biomarker of PTD, were enrolled in the study. The initial immunosuppressive scheme included azathioprine, cyclosporine, and steroids. After randomization, 18 patients (group 2) had their treatment modified by reducing cyclosporine dosage and substituting azathioprine for mycophenolate mofetil, while the other 15 patients (group 1) remained under the initial scheme. Patients were biopsied at enrollment and after 12 months of follow-up, and paired comparisons were performed between their intragraft gene expression profiles. The differential transcriptome profiles were analyzed by constructing gene co-expression networks and identifying enriched functions and central nodes in each network.ResultsOnly the alternative immunosuppressive scheme used in group 2 ameliorated renal function and tubular proteinuria after 12 months of follow-up. Intragraft molecular changes observed in group 2 were linked to autophagy, extracellular matrix, and adaptive immunity. Conversely, gene expression changes in group 1 were related to fibrosis, endocytosis, ubiquitination, and endoplasmic reticulum stress.ConclusionThese results suggest that molecular networks associated with the control of endocytosis, autophagy, protein overload, fibrosis, and adaptive immunity may be involved in improvement of graft function.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-015-0059-6) contains supplementary material, which is available to authorized users.

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Postmarketing evaluation of mycophenolate mofetil-based triple therapy immunosuppression compared with a conventional azathioprine-based regimen reveals enhanced efficacy and early pharmacoeconomic benefit after renal transplantation

Cited by 6 publications

References 4 publications

A Controlled Trial Comparing Two Doses of Cyclosporine in Conjunction with Mycophenolate Mofetil and Corticosteroids

A Controlled Trial Comparing Two Doses of Cyclosporine in Conjunction with Mycophenolate Mofetil and Corticosteroids

Update on Pharmacoeconomics in Transplantation

Intragraft transcriptional profiling of renal transplant patients with tubular dysfunction reveals mechanisms underlying graft injury and recovery

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