Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation.
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.
Tedesco-Silva
Helio
H
Setor de Transplante Renal, Hospital do Rim Hipertensão/ UNIFESP, Rua Borges, Lagoa, 960-11o andar, Sao Paulo, SP, Brazil. heliotedesco@hrim.com.br
Pescovitz
Mark D
MD
Cibrik
Diane
D
Rees
Michael A
MA
Mulgaonkar
Shamkant
S
Kahan
Barry D
BD
Gugliuzza
Kristene K
KK
Rajagopalan
P R
PR
Esmeraldo
Ronaldo de M
Rde M
Lord
Hélène
H
Salvadori
Maurizio
M
Slade
Jennifer M
JM
D000328:Adult; D003404:Creatinine / Q000652:urine; D016572:Cyclosporine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D003404:Creatinine; D000068876:Fingolimod Hydrochloride; D009173:Mycophenolic Acid; D013110:Sphingosine