ASSESSMENT OF TWO STRATEGIES OF NEORAL® ADMINISTRATION, EARLY VERSUS DELAYED, ON RENAL FUNCTION AND EFFICACY IN DE NOVO RENAL TRANSPLANT PATIENTS RECEIVING MYFORTIC®, STEROIDS AND ANTI-IL2R ANTIBODIES: 6 MONTHS INTERIM RESULTS OF A RANDOMIZED, MULTICENTRE, OPEN, PROSPECTIVE CONTROLLED STUDY

Abstract

P723 Background: the optimal immunosuppressive strategy and benefits of delaying Neoral® in order to prevent DGF risk has not been clearly established. Objectives: main objectives are assessment and comparison of renal function estimated by creatinine clearance (Cockcroft-Gault) at 3 m. and efficacy by treatment failure (BPAR, graft loss, death or lost to follow up) and BPAR at 6 m. after renal transplantation (RT). Methods: 203 1st or 2nd CAD or LRD de novo RT pts, were enrolled after a stratification according to the risk of DGF (US Renal Data System criteria). 197 pts were randomized to receive either Early (day 0; n=97) or Delayed (day 6; n=100) Neoral® (initial dose 8 mg/kg/d) in combination with Myfortic® an enteric-coated mycophenolate sodium (EC-MPS), (720 mg bid), steroids (centre practice) and anti-IL2R antibodies. Neoral® was adjusted using C-2h monitoring : mean target was 1300 (week 0-6), 1150 (week 6-12) and 900 ng/ml (month 4-6). 6 pts included but not randomized were excluded from this ITT analysis. Results: there was no significant difference in demographic and baseline parameters between the 2 groups. Risk of DGF(score ≥ 5) was also similar in both groups, 32/97 pts in E-Neoral® vs 33/100 pts in D-Neoral®. In the group of high risk of DGF, the incidence of DGF was 13/32 pts in E-Neoral® vs 14/33 pts in D-Neoral®. Pts who required dialysis during the first post Tx week were 26/97 (26.8%) and 23/100 (23%) in E vs D-Neoral® respectively (p=0.62). In ITT population, renal function at 3 m. was comparable; mean Creat. Clearance was 51.1±23.2 vs 53.8±24.4 mL/min (p=0.425) and mean SeCr was 178 vs 162 μmol/L, in E-Neoral® (n=97) and D-Neoral® (n=100) respectively (p=0.333). In PP population, mean Creat. Clearance was 54.6±20.0 vs 57.0±22.0 mL/min (p=0.453) and mean SeCr was 155 vs 141 μmol/L, in E-Neoral® (n=79) and D-Neoral® (n=91) respectively (p=0.149). In the 6 m. period, treatment failure was not statistically different in both groups, 24/97 (24.7%) in E-Neoral® vs 27/100 (27%) in D-Neoral® (p=ns). BPAR incidence was 18/97 (18.6%) in E-Neoral® vs 24/100 (24%) in D-Neoral® (p=ns). Severity of AR was mild (IA/IB) in 15/18 (83%) vs 20/24 (83%) respectively. A central evaluation of biopsies is ongoing and results will be presented Conclusion : These data suggest that there is no significant differential impact on renal function and efficacy of early vs delayed introduction of Neoral®, in combination with Myfortic® and steroids in RTP with or without risk of DGF.