Prednisone withdrawal, in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study

Nasimul Ahsan, Donald Hricik, Arthur Matas, Stephen Rose, Stephen Tomlanovich, Alan Wilkinson, Marian Ewell, Matthew McIntosh, Donald Stablein, Ernest Hodge, Daniel Hayes, Paul Gores, David Cohen, Thomas Gonwa, Karl Brinler, Robert Harland, John Neylan, Mark Pescovitz, James Wynn, Harold C-YangWilliam Bennett, John Copley, John Dunn, Steve Tomlanovich, Lawrence Chan, J. Andrew Bertolatus, Mathew Weir, Robert Mendez, John Pirsch, J. Harold Helderman

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

Background. 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. Methods. 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. Pre-study 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. Results. 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. Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)1865-1874
Number of pages10
JournalTransplantation
Volume68
Issue number12
StatePublished - Dec 27 1999
Externally publishedYes

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Mycophenolic Acid
Prednisone
Cyclosporine
Prospective Studies
Kidney
Clinical Trials Data Monitoring Committees
Treatment Failure
Antihypertensive Agents
Cholesterol
Transplants
Kaplan-Meier Estimate
Graft Survival
Transplant Recipients
Creatinine
Maintenance
Confidence Intervals
Incidence

ASJC Scopus subject areas

  • Transplantation

Cite this

Ahsan, N., Hricik, D., Matas, A., Rose, S., Tomlanovich, S., Wilkinson, A., ... Helderman, J. H. (1999). Prednisone withdrawal, in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study. Transplantation, 68(12), 1865-1874.

Prednisone withdrawal, in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study. / Ahsan, Nasimul; Hricik, Donald; Matas, Arthur; Rose, Stephen; Tomlanovich, Stephen; Wilkinson, Alan; Ewell, Marian; McIntosh, Matthew; Stablein, Donald; Hodge, Ernest; Hayes, Daniel; Gores, Paul; Cohen, David; Gonwa, Thomas; Brinler, Karl; Harland, Robert; Neylan, John; Pescovitz, Mark; Wynn, James; C-Yang, Harold; Bennett, William; Copley, John; Dunn, John; Tomlanovich, Steve; Chan, Lawrence; Bertolatus, J. Andrew; Weir, Mathew; Mendez, Robert; Pirsch, John; Helderman, J. Harold.

In: Transplantation, Vol. 68, No. 12, 27.12.1999, p. 1865-1874.

Research output: Contribution to journalArticle

Ahsan, N, Hricik, D, Matas, A, Rose, S, Tomlanovich, S, Wilkinson, A, Ewell, M, McIntosh, M, Stablein, D, Hodge, E, Hayes, D, Gores, P, Cohen, D, Gonwa, T, Brinler, K, Harland, R, Neylan, J, Pescovitz, M, Wynn, J, C-Yang, H, Bennett, W, Copley, J, Dunn, J, Tomlanovich, S, Chan, L, Bertolatus, JA, Weir, M, Mendez, R, Pirsch, J & Helderman, JH 1999, 'Prednisone withdrawal, in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study', Transplantation, vol. 68, no. 12, pp. 1865-1874.
Ahsan N, Hricik D, Matas A, Rose S, Tomlanovich S, Wilkinson A et al. Prednisone withdrawal, in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study. Transplantation. 1999 Dec 27;68(12):1865-1874.
Ahsan, Nasimul ; Hricik, Donald ; Matas, Arthur ; Rose, Stephen ; Tomlanovich, Stephen ; Wilkinson, Alan ; Ewell, Marian ; McIntosh, Matthew ; Stablein, Donald ; Hodge, Ernest ; Hayes, Daniel ; Gores, Paul ; Cohen, David ; Gonwa, Thomas ; Brinler, Karl ; Harland, Robert ; Neylan, John ; Pescovitz, Mark ; Wynn, James ; C-Yang, Harold ; Bennett, William ; Copley, John ; Dunn, John ; Tomlanovich, Steve ; Chan, Lawrence ; Bertolatus, J. Andrew ; Weir, Mathew ; Mendez, Robert ; Pirsch, John ; Helderman, J. Harold. / Prednisone withdrawal, in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study. In: Transplantation. 1999 ; Vol. 68, No. 12. pp. 1865-1874.
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title = "Prednisone withdrawal, in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study",
abstract = "Background. 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. Methods. 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. Pre-study 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. Results. 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. Conclusions. 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.",
author = "Nasimul Ahsan and Donald Hricik and Arthur Matas and Stephen Rose and Stephen Tomlanovich and Alan Wilkinson and Marian Ewell and Matthew McIntosh and Donald Stablein and Ernest Hodge and Daniel Hayes and Paul Gores and David Cohen and Thomas Gonwa and Karl Brinler and Robert Harland and John Neylan and Mark Pescovitz and James Wynn and Harold C-Yang and William Bennett and John Copley and John Dunn and Steve Tomlanovich and Lawrence Chan and Bertolatus, {J. Andrew} and Mathew Weir and Robert Mendez and John Pirsch and Helderman, {J. Harold}",
year = "1999",
month = "12",
day = "27",
language = "English (US)",
volume = "68",
pages = "1865--1874",
journal = "Transplantation",
issn = "0041-1337",
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}

TY - JOUR

T1 - Prednisone withdrawal, in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study

AU - Ahsan, Nasimul

AU - Hricik, Donald

AU - Matas, Arthur

AU - Rose, Stephen

AU - Tomlanovich, Stephen

AU - Wilkinson, Alan

AU - Ewell, Marian

AU - McIntosh, Matthew

AU - Stablein, Donald

AU - Hodge, Ernest

AU - Hayes, Daniel

AU - Gores, Paul

AU - Cohen, David

AU - Gonwa, Thomas

AU - Brinler, Karl

AU - Harland, Robert

AU - Neylan, John

AU - Pescovitz, Mark

AU - Wynn, James

AU - C-Yang, Harold

AU - Bennett, William

AU - Copley, John

AU - Dunn, John

AU - Tomlanovich, Steve

AU - Chan, Lawrence

AU - Bertolatus, J. Andrew

AU - Weir, Mathew

AU - Mendez, Robert

AU - Pirsch, John

AU - Helderman, J. Harold

PY - 1999/12/27

Y1 - 1999/12/27

N2 - Background. 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. Methods. 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. Pre-study 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. Results. 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. Conclusions. 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.

AB - Background. 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. Methods. 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. Pre-study 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. Results. 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. Conclusions. 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.

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