2010 - TTS International Congress


Clinical Immunosuppression Kidney late

19.9 - A prospective multicenter open-label randomized study to assess efficacy and safety of everolimus with ciclosporine-microemulsion (CsA-ME) versus everolimus without calcineurine inhibitor with mycophenolate sodium, in maintenance adult kidney transplant p

Presenter: Elisabeth, CASSUTO, Nice, France
Authors: CASSUTO E., Berthoux F., TOUPANCE O., MOULIN B., MOAL M., QUERE S., CHAOUCHE-TEYARA K., Dantal J.


A PROSPECTIVE MULTICENTER OPEN-LABEL RANDOMIZED STUDY TO ASSESS EFFICACY AND SAFETY OF EVEROLIMUS WITH CICLOSPORINE-MICROEMULSION (CSA-ME) VERSUS EVEROLIMUS WITHOUT CALCINEURINE INHIBITOR WITH MYCOPHENOLATE SODIUM, IN MAINTENANCE ADULT KIDNEY TRANSPLANT PATIENTS : FOREVER STUDY

CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

E. Cassuto1, F. Berthoux2, O. Toupance2, B. Moulin2, M.C. Moal2, S. Quere2, K. Chaouche-teyara2, J. Dantal2
1Service De Néphrologie- Pavillon A, Hôpital Pasteur, Nice/FRANCE, 2Service De Néphrologie- Pavillon A, Hôpital Pasteur, On behalf of FOREVER French Group/FRANCE

Body:
Introduction: it is currently admitted that high or prolonged CNI exposure may induce more or less rapidly an alteration of glomerular filtration (GFR) and facilitate IF/TA progression. There is high interest to evaluate efficacy and safety of CNI withdrawal based on everolimus (EVR) with mycophenolate sodium (EC-MPS) on GFR and IF/TA development, in adult kidney transplant (AKTx) patients in maintenance. Study population consists of AKTx patients at 12 months post- Tx having taken part to Callisto study (Albano et al. Transplantation, 88- 2009) and who had not prematurely discontinued immunosuppressive regimen (everolimus with CsA-ME and steroids). Methods: 30 patients were randomized at 12 months post- Tx to either continuo CNI (CNI control group, n=15) with EVR (3≤C0≤8 ng/ml) or to CNI withdrawal (CNI free group, n=15) with EVR (6≤C0≤10 ng/ml) plus EC-MPS 720 mg/d. All patients received oral steroids (5-10 mg/d). Objectives: Primary is to compare GFR outcome measured by iohexol plasmatic clearance at M12 (24 months after Tx), to demonstrate non-inferiority (NI) for CNI free group with a NI margin of 5 ml/min. Secondary are renal function at M3, M6 and M12, treatment failure (BPAR, graft loss/re Tx, death or loss to follow-up) at M6 and M12, IF/TA at M12 and safety. Efficacy results are on ITT population and safety results on safety population. Results: Baseline demographics were statistically comparable between both groups. 96.7% were Caucasians, 80% were Male, average age was 60.6 years and mean BMI was 25.6 kg/m2. 5 patients (16.7%) discontinued study treatment due to AE (3), death (1), consent withdrawal (1). From baseline to M12, GFR outcome did not differ statistically between 2 groups: CNI -4.07 ml/min vs CNI free 10.30 ml/min (p=0.0587). 95% CI of the difference is [-29.31;0.57], demonstrating NI of CNI free group. Renal function (aMDRD) was not statistically different at M3 (median, CNI: 42.0 vs CNI free: 47.9; p= 0.404) and M6 (median, CNI: 39.7 vs CNI free: 47.8; p=0.165 ). At M12, there is a significant difference (median, CNI: 38.0 vs CNI free: 57.7 mL/min/1.73m2 (p=0.012). At M6 and M12, treatment failure did not differ : 0/0 (CNI/CNI free) at M6 and 2/0 (p= 0.222) at M12. BPAR was 1/13 CNI (7.7%) vs 0/14 CNI free (p=0.481) at M12. A renal biopsy was realized at baseline and at M12 (end of study; M24 post Tx) in 5/13 CNI vs 9/14 in CNI free patients. No lesions were observed in 4/5 CNI vs 7/9 in CNI free at M12. 2/5 in CNI free had IF/TA only at baseline and 1/5 had IF/TA lesions at baseline confirmed at M12. No graft loss in both groups and 1 death in CNI group. 5/30 (16.7%) discontinued study medication, mainly for AE (4/5) : 4 in CNI vs 1 CNI free. Most common AEs were: peripheral oedema (9/30, 30%), anemia (6/30, 20%), dyslipidaemia (5/30, 16.7%).Conclusion: This study demonstrate efficacy and safety of a CNI free regimen from 12 monthspost transplantation based on everolimus, mycophenolate sodium and steroids, in AKTx patients in maintenance.

Disclosure: All authors have declared no conflicts of interest.


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