title: FTY720 versus mycophenolate mofetil in de novo renal transplantation: six-month results of a double-blind study.
abstract: 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.
authors.affiliation: Setor de Transplante Renal, Hospital do Rim Hipertensão/ UNIFESP, Rua Borges Lagoa, Sao Paulo, Brazil. heliotedesco@hrim.com.br
authors.forename: Helio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: Peter
authors.initials: P
authors.lastname: Szakaly
authors.forename: Ahmed
authors.initials: A
authors.lastname: Shoker
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommerer
authors.forename: Norio
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Schena
authors.forename: Malika
authors.initials: M
authors.lastname: Cremer
authors.forename: Abdel
authors.initials: A
authors.lastname: Hmissi
authors.forename: Hartmut
authors.initials: H
authors.lastname: Mayer
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D009173:Mycophenolic Acid; D013110:Sphingosine