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

Background. Phase 11 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.UNIFESP, Hosp Rim Hipertensao, Setor Transplante Renal, BR-04038002 São Paulo, SP, BrazilIndiana Univ, Indianapolis, in USAUniv Michigan, Hlth Syst, Ann Arbor, MI USAUniv Toledo, Med Ctr, Dept Urol, Toledo, OH 43606 USASt Barnabas Hosp, Livingston, NJ USAUniv Texas, Houston Med Sch, Div Immunol & Organ Transplantat, Houston, TX USAUniv Texas, Med Branch, John Sealy Hosp, Galveston, TX 77550 USAMed Univ S Carolina, Charleston, SC 29425 USAHosp Geral Fortaleza, Setor Transplante Renal, Fortaleza, Ceara, BrazilHop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, CanadaCareggi Univ Hosp, Renal Unit, Florence, ItalyNovartis Pharmaceut Corp, E Hanover, NJ USAUNIFESP, Hosp Rim Hipertensao, Setor Transplante Renal, BR-04038002 São Paulo, SP, BrazilWeb of Scienc