FTY720 versus mycophenolate mofetil in de novo renal transplantation: six-month results of a double-blind study.
BACKGROUND
FTY720 is a novel immunomodulator that was developed to produce optimal graft protection with improved safety and tolerability. Phase II studies have demonstrated the efficacy of FTY720 up to the doses of 2.5 mg with full-dose cyclosporine (FDC).


METHODS
This multicenter, double-blind, Phase IIb, randomized study evaluated the safety and efficacy of 5 mg FTY720 (n=87; Group 1) vs. 2.5 mg FTY720 (n=90; Group 2) vs. mycophenolate mofetil (MMF; n=94; Group 3) in de novo renal transplant patients receiving FDC and prednisone.


RESULTS
The primary efficacy endpoint was the occurrence of treated biopsy-proven acute rejection, graft loss, death, or premature study discontinuation (composite endpoint) within 6 months. The primary endpoint was superior in Group 1 (24%) and statistically noninferior in Group 2 compared to Group 3 (24.1% vs. 29.2% vs. 39.4%; P=0.025 and 0.0039, respectively). FTY720 plus FDC was generally well tolerated, with a similar incidence of adverse events across all groups. FTY720 was associated with higher incidence of bradycardia (Group 1: 26.4%, P=0.0002 and Group 2: 15.6%, P=0.046, vs. Group 3: 6.4%), respiratory disorders (Group 1: 40.2%, not significant [P=NS] and Group 2: 34.4%, P=NS vs. Group 3: 28.7%). One macular edema occurred in Group 2. Lower creatinine clearances were observed with FTY720 versus MMF (Group 1: 52.4 ml/min, P=NS and Group 2: 51.7 ml/min, P=0.039 vs. Group 3: 62.5 ml/min).


CONCLUSIONS
Although FTY720 with FDC provided adequate protection from acute rejection the safety profile was less favorable for adverse events than current standard immunosuppression in de novo renal transplant patients.
Tedesco-Silva
Helio
H
Setor de Transplante Renal, Hospital do Rim Hipertensão/ UNIFESP, Rua Borges Lagoa, Sao Paulo, Brazil. heliotedesco@hrim.com.br
Szakaly
Peter
P
Shoker
Ahmed
A
Sommerer
Claudia
C
Yoshimura
Norio
N
Schena
Francesco Paolo
FP
Cremer
Malika
M
Hmissi
Abdel
A
Mayer
Hartmut
H
Lang
Philippe
P
D000328:Adult; D001706:Biopsy; D001919:Bradycardia / Q000378:metabolism; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011409:Propylene Glycols / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D009173:Mycophenolic Acid; D013110:Sphingosine