PREDNISONE WITHDRAWAL IN KIDNEY TRANSPLANT RECIPIENTS ON CYCLOSPORINE AND MYCOPHENOLATE MOFETIL-A PROSPECTIVE RANDOMIZED STUDY1,2
- 1 December 1999
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Transplantation
- Vol. 68 (12), 1865-1874
- https://doi.org/10.1097/00007890-199912270-00009
Abstract
Prospective randomized trials have shown a reduced rate of acute rejection (AR) in mycophenolate mofetil-treated kidney transplant recipients. We hypothesized that this increased protection from AR could allow successful prednisone (P) withdrawal in cyclosporine/mycophenolate mofetil/P-treated recipients. A multicenter, prospective, randomized, double-blind trial of P withdrawal at 3 months posttransplant was initiated. Entry criteria were: primary transplant, adult, no AR by 90 days, mycophenolate mofetil dose ≥2 g/day, cyclosporine dose=5-15 mg/kg/day, P dose=10-15 mg/day. Study participants were randomized to have P tapered over 8 weeks (beginning at 3 months posttransplant) to 0 vs. 10 mg/day. Prestudy power analysis determined 500 recipients should be randomized for 80% statistical power to test equivalence of the primary endpoint, AR, or treatment failure at 1 year posttransplant. By design, the study was to be stopped if interim data precluded reaching equivalence. An established data safety monitoring board monitored the study. After 266 patients were enrolled, the patient enrollment was stopped (after safety monitoring board review) because of excess rejection in the P withdrawal group. The Kaplan-Meier estimate of the cumulative incidence of rejection or treatment failure within 1 year posttransplant (±95% confidence interval) for the maintenance group was 9.8% (4.4%; treatment failure, 14.9%); for the withdrawal group, 30.8% (21.0%; 39.3%). Treatment differences in the distribution of time to event were highly significant (P=0.0007). Of note, risk was higher in blacks (39.6%) versus nonblacks (16.0%) (P<0.001). At 1 year posttransplant, there was no difference between groups in patient or graft survival. For the patients with functioning grafts at 6 months posttransplant, withdrawal patients had lower cholesterol (P=0.0005), had higher creatinine (P=0.03), and were less likely to use antihypertensives (P=0.001). These differences persist to 1 yr posttransplant. We conclude that for recipients on cyclosporine/mycophenolate mofetil/P with no AR at 90 days, the chance of developing subsequent AR is small; if P is tapered and withdrawn, the risk increases (but the majority remain free of acute and chronic rejection). After withdrawal, the risk of AR is different for blacks versus nonblacks. Withdrawal patients had a lower cholesterol level and less need for antihypertensives.Keywords
This publication has 29 references indexed in Scilit:
- Corticosteroid Withdrawal after Renal Transplantation in the Cyclosporin EraBioDrugs, 1997
- STEROID WITHDRAWAL IN MYCOPHENOLATE MOFETIL-TREATED RENAL ALLOGRAFT RECIPIENTSTransplantation, 1997
- RANDOMIZED, PROSPECTIVE TRIAL OF CYCLOSPORINE MONOTHERAPY VERSUS AZATHIOPRINE-PREDNISONE FROM THREE MONTHS AFTER RENAL TRANSPLANTATION1Transplantation, 1996
- Interaction between the 67 kilodalton metastasis-associated laminin receptor and lamininKidney International, 1993
- WITHDRAWAL OF STEROIDS AFTER RENAL TRANSPLANTATION—CLINICAL PREDICTORS OF OUTCOME1Transplantation, 1992
- A RANDOMIZED PROSPECTIVE TRIAL COMPARING CYCLOSPORINE MONOTHERAPY WITH TRIPLE-DRUG THERAPY IN RENAL TRANSPLANTATIONTransplantation, 1991
- A PROSPECTIVE RANDOMIZED TRIAL OF PREDNISONE VERSUS NO PREDNISONE MAINTENANCE THERAPY IN CYCLOSPORINE-TREATED AND AZATHIOPRINE-TREATED RENAL TRANSPLANT PATIENTSTransplantation, 1990
- COMPLETE REPLACEMENT OF METHYLPREDNISOLONE BY AZATHIOPRINE IN CYCLOSPORINE-TREATED PRIMARY CADAVERIC RENAL TRANSPLANT RECIPIENTS1 Pressented at the 6th Annual Meeting of the American Society of Transplant Physicians, May 1987, Chicago, ILTransplantation, 1988
- Diagnosis of Creutzfeldt-Jakob Disease by Western Blot Identification of Marker Protein in Human Brain TissueNew England Journal of Medicine, 1986
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958