Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation

Helio Tedesco-Silva, Mark D. Pescovitz, Diane Cibrik, Michael A. Rees, Shamkant Mulgaonkar, Barry D. Kahan, Kristene Gugliuzza, P. R. Rajagopalan, Ronaldo De M Esmeraldo, Hélène Lord, Maurizio Salvadori, Jennifer M. Slade

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

BACKGROUND. Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. METHODS. This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. RESULTS. FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3%). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. CONCLUSIONS. While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.

Original languageEnglish (US)
Pages (from-to)1689-1697
Number of pages9
JournalTransplantation
Volume82
Issue number12
DOIs
StatePublished - Dec 2006

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Mycophenolic Acid
Kidney Transplantation
Cyclosporine
Randomized Controlled Trials
Fingolimod Hydrochloride
Creatinine
Transplants
Premature Mortality
Incidence
Immunologic Factors

Keywords

  • Cyclosporine
  • FTY720
  • Mycophenolate mofetil
  • Renal transplantation
  • Sphingosine inhibitors

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Tedesco-Silva, H., Pescovitz, M. D., Cibrik, D., Rees, M. A., Mulgaonkar, S., Kahan, B. D., ... Slade, J. M. (2006). Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation. Transplantation, 82(12), 1689-1697. https://doi.org/10.1097/01.tp.0000251718.95622.b3

Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation. / Tedesco-Silva, Helio; Pescovitz, Mark D.; Cibrik, Diane; Rees, Michael A.; Mulgaonkar, Shamkant; Kahan, Barry D.; Gugliuzza, Kristene; Rajagopalan, P. R.; Esmeraldo, Ronaldo De M; Lord, Hélène; Salvadori, Maurizio; Slade, Jennifer M.

In: Transplantation, Vol. 82, No. 12, 12.2006, p. 1689-1697.

Research output: Contribution to journalArticle

Tedesco-Silva, H, Pescovitz, MD, Cibrik, D, Rees, MA, Mulgaonkar, S, Kahan, BD, Gugliuzza, K, Rajagopalan, PR, Esmeraldo, RDM, Lord, H, Salvadori, M & Slade, JM 2006, 'Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation', Transplantation, vol. 82, no. 12, pp. 1689-1697. https://doi.org/10.1097/01.tp.0000251718.95622.b3
Tedesco-Silva H, Pescovitz MD, Cibrik D, Rees MA, Mulgaonkar S, Kahan BD et al. Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation. Transplantation. 2006 Dec;82(12):1689-1697. https://doi.org/10.1097/01.tp.0000251718.95622.b3
Tedesco-Silva, Helio ; Pescovitz, Mark D. ; Cibrik, Diane ; Rees, Michael A. ; Mulgaonkar, Shamkant ; Kahan, Barry D. ; Gugliuzza, Kristene ; Rajagopalan, P. R. ; Esmeraldo, Ronaldo De M ; Lord, Hélène ; Salvadori, Maurizio ; Slade, Jennifer M. / Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation. In: Transplantation. 2006 ; Vol. 82, No. 12. pp. 1689-1697.
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abstract = "BACKGROUND. Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. METHODS. This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. RESULTS. FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8{\%} and 30.6{\%}) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3{\%}). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. CONCLUSIONS. While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50{\%} reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.",
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AU - Mulgaonkar, Shamkant

AU - Kahan, Barry D.

AU - Gugliuzza, Kristene

AU - Rajagopalan, P. R.

AU - Esmeraldo, Ronaldo De M

AU - Lord, Hélène

AU - Salvadori, Maurizio

AU - Slade, Jennifer M.

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N2 - BACKGROUND. Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. METHODS. This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. RESULTS. FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3%). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. CONCLUSIONS. While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.

AB - BACKGROUND. Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. METHODS. This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. RESULTS. FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3%). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. CONCLUSIONS. While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.

KW - Cyclosporine

KW - FTY720

KW - Mycophenolate mofetil

KW - Renal transplantation

KW - Sphingosine inhibitors

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