Rad in de novo renal transplantation: Comparison of three doses on the incidence and severity of acute rejection

Barry D. Kahan, B. Kaplan, M. I. Lorber, M. Winkler, N. Cambon, R. S. Boger

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Background. The effects of three doses of RAD (40-O-[2-hydroxyethyl]-rapamycin), a novel macrolide with potent immunosuppressive and antiproliferative properties, on the incidence and severity of acute rejection episodes as well as its tolerability were evaluated in a dose-ranging study in de novo renal transplant recipients. Methods. In this double-blind, parallel group, multicenter study, recipients were randomized to receive 1 mg, 2 mg, or 4 mg/day of RAD in combination with Neoral® (cyclosporine, USP MODIFIED) and corticosteroids. The incidence and severity of biopsy-proven acute rejection episodes, graft survival, patient survival, infection rates, laboratory measurements, and adverse events were compared across groups after 6 months of therapy. Results. Among the 103 recipients, patients receiving 1, 2, or 4 mg/day experienced a 32.4%, 14.7%, or 25.7% incidence of biopsy-proven acute rejection episodes within the first 6 months posttransplantation, respectively. Even though the study was not powered to demonstrate efficacy, the incidence of moderate and severe acute rejection episodes was found to be significantly lower among patients in the 2 mg and 4 mg/day groups than in the 1 mg/day group (P=0.002 and P=0.006, respectively). Overall graft and patient survival rates were excellent. RAD was generally well tolerated. Although blood lipid levels increased in all groups, changes were manageable with lipid-lowering agents and did not warrant discontinuation of study medication. The incidence of viral and fungal infections was low; however, it was higher among recipients treated with 4 mg/day. Conclusions. In combination with Neoral® and corticosteroids, RAD doses of 2 mg and 4 mg/day resulted in lower rates of acute rejection episodes and efficacy failure than the 1 mg/day dose and were significantly more effective in reducing the severity of rejection. Large-scale, controlled, follow-up studies are currently in progress to confirm these initial findings.

Original languageEnglish (US)
Pages (from-to)1400-1406
Number of pages7
JournalTransplantation
Volume71
Issue number10
StatePublished - May 27 2001
Externally publishedYes

Fingerprint

Kidney Transplantation
Incidence
Cyclosporine
Graft Survival
Adrenal Cortex Hormones
Survival Rate
Laboratory Infection
Lipids
Biopsy
Mycoses
Macrolides
Virus Diseases
Immunosuppressive Agents
Multicenter Studies
Kidney
Therapeutics

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Kahan, B. D., Kaplan, B., Lorber, M. I., Winkler, M., Cambon, N., & Boger, R. S. (2001). Rad in de novo renal transplantation: Comparison of three doses on the incidence and severity of acute rejection. Transplantation, 71(10), 1400-1406.

Rad in de novo renal transplantation : Comparison of three doses on the incidence and severity of acute rejection. / Kahan, Barry D.; Kaplan, B.; Lorber, M. I.; Winkler, M.; Cambon, N.; Boger, R. S.

In: Transplantation, Vol. 71, No. 10, 27.05.2001, p. 1400-1406.

Research output: Contribution to journalArticle

Kahan, BD, Kaplan, B, Lorber, MI, Winkler, M, Cambon, N & Boger, RS 2001, 'Rad in de novo renal transplantation: Comparison of three doses on the incidence and severity of acute rejection', Transplantation, vol. 71, no. 10, pp. 1400-1406.
Kahan BD, Kaplan B, Lorber MI, Winkler M, Cambon N, Boger RS. Rad in de novo renal transplantation: Comparison of three doses on the incidence and severity of acute rejection. Transplantation. 2001 May 27;71(10):1400-1406.
Kahan, Barry D. ; Kaplan, B. ; Lorber, M. I. ; Winkler, M. ; Cambon, N. ; Boger, R. S. / Rad in de novo renal transplantation : Comparison of three doses on the incidence and severity of acute rejection. In: Transplantation. 2001 ; Vol. 71, No. 10. pp. 1400-1406.
@article{a7e03dba48844186a7a70f1deb9bcc8b,
title = "Rad in de novo renal transplantation: Comparison of three doses on the incidence and severity of acute rejection",
abstract = "Background. The effects of three doses of RAD (40-O-[2-hydroxyethyl]-rapamycin), a novel macrolide with potent immunosuppressive and antiproliferative properties, on the incidence and severity of acute rejection episodes as well as its tolerability were evaluated in a dose-ranging study in de novo renal transplant recipients. Methods. In this double-blind, parallel group, multicenter study, recipients were randomized to receive 1 mg, 2 mg, or 4 mg/day of RAD in combination with Neoral{\circledR} (cyclosporine, USP MODIFIED) and corticosteroids. The incidence and severity of biopsy-proven acute rejection episodes, graft survival, patient survival, infection rates, laboratory measurements, and adverse events were compared across groups after 6 months of therapy. Results. Among the 103 recipients, patients receiving 1, 2, or 4 mg/day experienced a 32.4{\%}, 14.7{\%}, or 25.7{\%} incidence of biopsy-proven acute rejection episodes within the first 6 months posttransplantation, respectively. Even though the study was not powered to demonstrate efficacy, the incidence of moderate and severe acute rejection episodes was found to be significantly lower among patients in the 2 mg and 4 mg/day groups than in the 1 mg/day group (P=0.002 and P=0.006, respectively). Overall graft and patient survival rates were excellent. RAD was generally well tolerated. Although blood lipid levels increased in all groups, changes were manageable with lipid-lowering agents and did not warrant discontinuation of study medication. The incidence of viral and fungal infections was low; however, it was higher among recipients treated with 4 mg/day. Conclusions. In combination with Neoral{\circledR} and corticosteroids, RAD doses of 2 mg and 4 mg/day resulted in lower rates of acute rejection episodes and efficacy failure than the 1 mg/day dose and were significantly more effective in reducing the severity of rejection. Large-scale, controlled, follow-up studies are currently in progress to confirm these initial findings.",
author = "Kahan, {Barry D.} and B. Kaplan and Lorber, {M. I.} and M. Winkler and N. Cambon and Boger, {R. S.}",
year = "2001",
month = "5",
day = "27",
language = "English (US)",
volume = "71",
pages = "1400--1406",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Rad in de novo renal transplantation

T2 - Comparison of three doses on the incidence and severity of acute rejection

AU - Kahan, Barry D.

AU - Kaplan, B.

AU - Lorber, M. I.

AU - Winkler, M.

AU - Cambon, N.

AU - Boger, R. S.

PY - 2001/5/27

Y1 - 2001/5/27

N2 - Background. The effects of three doses of RAD (40-O-[2-hydroxyethyl]-rapamycin), a novel macrolide with potent immunosuppressive and antiproliferative properties, on the incidence and severity of acute rejection episodes as well as its tolerability were evaluated in a dose-ranging study in de novo renal transplant recipients. Methods. In this double-blind, parallel group, multicenter study, recipients were randomized to receive 1 mg, 2 mg, or 4 mg/day of RAD in combination with Neoral® (cyclosporine, USP MODIFIED) and corticosteroids. The incidence and severity of biopsy-proven acute rejection episodes, graft survival, patient survival, infection rates, laboratory measurements, and adverse events were compared across groups after 6 months of therapy. Results. Among the 103 recipients, patients receiving 1, 2, or 4 mg/day experienced a 32.4%, 14.7%, or 25.7% incidence of biopsy-proven acute rejection episodes within the first 6 months posttransplantation, respectively. Even though the study was not powered to demonstrate efficacy, the incidence of moderate and severe acute rejection episodes was found to be significantly lower among patients in the 2 mg and 4 mg/day groups than in the 1 mg/day group (P=0.002 and P=0.006, respectively). Overall graft and patient survival rates were excellent. RAD was generally well tolerated. Although blood lipid levels increased in all groups, changes were manageable with lipid-lowering agents and did not warrant discontinuation of study medication. The incidence of viral and fungal infections was low; however, it was higher among recipients treated with 4 mg/day. Conclusions. In combination with Neoral® and corticosteroids, RAD doses of 2 mg and 4 mg/day resulted in lower rates of acute rejection episodes and efficacy failure than the 1 mg/day dose and were significantly more effective in reducing the severity of rejection. Large-scale, controlled, follow-up studies are currently in progress to confirm these initial findings.

AB - Background. The effects of three doses of RAD (40-O-[2-hydroxyethyl]-rapamycin), a novel macrolide with potent immunosuppressive and antiproliferative properties, on the incidence and severity of acute rejection episodes as well as its tolerability were evaluated in a dose-ranging study in de novo renal transplant recipients. Methods. In this double-blind, parallel group, multicenter study, recipients were randomized to receive 1 mg, 2 mg, or 4 mg/day of RAD in combination with Neoral® (cyclosporine, USP MODIFIED) and corticosteroids. The incidence and severity of biopsy-proven acute rejection episodes, graft survival, patient survival, infection rates, laboratory measurements, and adverse events were compared across groups after 6 months of therapy. Results. Among the 103 recipients, patients receiving 1, 2, or 4 mg/day experienced a 32.4%, 14.7%, or 25.7% incidence of biopsy-proven acute rejection episodes within the first 6 months posttransplantation, respectively. Even though the study was not powered to demonstrate efficacy, the incidence of moderate and severe acute rejection episodes was found to be significantly lower among patients in the 2 mg and 4 mg/day groups than in the 1 mg/day group (P=0.002 and P=0.006, respectively). Overall graft and patient survival rates were excellent. RAD was generally well tolerated. Although blood lipid levels increased in all groups, changes were manageable with lipid-lowering agents and did not warrant discontinuation of study medication. The incidence of viral and fungal infections was low; however, it was higher among recipients treated with 4 mg/day. Conclusions. In combination with Neoral® and corticosteroids, RAD doses of 2 mg and 4 mg/day resulted in lower rates of acute rejection episodes and efficacy failure than the 1 mg/day dose and were significantly more effective in reducing the severity of rejection. Large-scale, controlled, follow-up studies are currently in progress to confirm these initial findings.

UR - http://www.scopus.com/inward/record.url?scp=0035958104&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035958104&partnerID=8YFLogxK

M3 - Article

C2 - 11391226

AN - SCOPUS:0035958104

VL - 71

SP - 1400

EP - 1406

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 10

ER -