FTY720 versus MMF with cyclosporine in de novo renal transplantation: a 1-year, randomized controlled trial in Europe and Australasia.
FTY720 is a novel immunomodulator investigated in de novo renal transplantation and other therapeutic areas including multiple sclerosis. This 1-year multicenter, randomized, phase III study in 668 de novo renal transplant patients compared FTY720 2.5 mg plus full-dose cyclosporine (FDC) or FTY720 5.0 mg plus reduced-dose cyclosporine (RDC), with mycophenolate mofetil (MMF) plus FDC. The primary efficacy endpoint was the composite incidence of first treated biopsy-proven acute rejection (BPAR), graft loss, death or premature study discontinuation at month 12. Primary efficacy with FTY720 2.5 mg and MMF (32.4% and 30.2%; p = NS), plus mortality and BPAR incidence, were comparable. Patients receiving FTY720 5.0 mg plus RDC were discontinued from treatment due to increased risk of acute rejection (primary endpoint incidence 47.3%). FTY720 was associated with lower creatinine clearance (month 12: 53.1, 56.0 vs. 65.1 mL/min; p < 0.001) and more macular edema cases (2.2% and 1.3% vs. 0%), whereas cytomegalovirus infections were higher with MMF (6.2% and 10.6% vs. 18.1% p < 0.0001 and p = 0.0139, respectively). FTY720 2.5 mg provided comparable rejection prophylaxis over 12 months versus MMF; however, FTY720 5.0 mg did not support a 50% reduction in cyclosporine exposure. The cause of macular edema cases and lower creatinine clearance with FTY720 in de novo transplantation needs further investigation.
Salvadori
M
M
Careggi Hospital, Division of Nephrology, Florence, Italy. salvadorim@ao-careggi.toscana.it
Budde
K
K
Charpentier
B
B
Klempnauer
J
J
Nashan
B
B
Pallardo
L M
LM
Eris
J
J
Schena
F P
FP
Eisenberger
U
U
Rostaing
L
L
Hmissi
A
A
Aradhye
S
S
D000328:Adult; D044362:Australasia; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005060:Europe; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival / Q000276:immunology / Q000502:physiology*; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008111:Liver Function Tests; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011409:Propylene Glycols / Q000627:therapeutic use*; D012449:Safety; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D011409:Propylene Glycols; D016572:Cyclosporine; D003404:Creatinine; D000068876:Fingolimod Hydrochloride; D009173:Mycophenolic Acid; D013110:Sphingosine