ESPN 50th Annual Meeting

ESPN 2017


 
PRESERVATION OF RENAL FUNCTION WITH EVEROLIMUS PLUS REDUCED-DOSE TACROLIMUS AND CORTICOSTEROID WITHDRAWAL-BASED REGIMEN IN DE NOVO PEDIATRIC RENAL TRANSPLANT RECIPIENTS: 12-MONTH RESULTS FROM THE CRADLE STUDY
Burkhard Tönshoff 1 Robert Ettenger 2 Luca Dello Strologo 3 Stephen D Marks 4 Lars Pape 5 Martin Christian 6 Zoltan Mathe 7 El-Djouher Martzloff 8 Barbara Rauer 8 Jennifer Ng 9 Matthias Meier 8 Patricia M Lopez 8

1- DEPARTMENT OF PEDIATRICS I, UNIVERSITY CHILDRENS HOSPITAL OF HEIDELBERG, HEIDELBERG, GERMANY
2- DIVISION OF PEDIATRIC NEPHROLOGY, UCLA MATTEL CHILDREN’S HOSPITAL, LOS ANGELES, CA, UNITED STATES
3- NEPHROLOGY AND TRANSPLANT UNIT, BAMBINO GESù CHILDRENS HOSPITAL IRCCS, ROME, ITALY
4- DEPARTMENT OF PEDIATRIC NEPHROLOGY, GREAT ORMOND STREET HOSPITAL FOR CHILDREN NHS FOUNDATION TRUST, LONDON, UNITED KINGDOM
5- DEPARTMENT OF PEDIATRIC NEPHROLOGY, HANNOVER MEDICAL SCHOOL, HANNOVER, GERMANY
6- DEPARTMENT OF PEDIATRIC NEPHROLOGY, NOTTINGHAM CHILDRENS HOSPITAL, NOTTINGHAM UNIVERSITY HOSPITALS NHS TRUST, NOTTINGHAM, UNITED KINGDOM
7- DEPARTMENT OF TRANSPLANTATION AND SURGERY, SEMMELWEIS UNIVERSITY, BUDAPEST, HUNGARY
8- NOVARTIS PHARMA AG, BASEL, SWITZERLAND
9- NOVARTIS PHARMACEUTICALS CORPORATION, EAST HANOVER, NJ, UNITED STATES
 
Introduction:

CRADLE (NCT01544491) study evaluated the efficacy and safety of everolimus with reduced-dose tacrolimus (EVR+rTAC) and early corticosteroid (CS) withdrawal regimen in pediatric renal transplant recipients (pRTxR). Here, we report the 12-month (M) renal function outcomes from the study.

Material and methods:

In this 12M core+24M follow-up, phase III, multicenter, open-label study, pRTxR (≥1-<18 years) on mycophenolate mofetil (MMF)+standard-dose TAC (sTAC)+CS were randomized (1:1) at 4-6 weeks post-Tx to EVR+rTAC with CS withdrawal at 6M (EVR C0:3-8ng/mL; TAC C0:randomization [RND]-M3, 4-6ng/mL; from M4, 2-4ng/mL); or sTAC+MMF+CS (TAC C0:RND-M3, 7-10ng/mL; from M4, 5-8ng/mL). Co-primary objectives were to evaluate renal function (eGFR; updated Schwartz) and composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at M12. Other objectives included overall safety.

Results:

Of 106 (EVR+rTAC, N=52 and MMF+sTAC, N=54) patients randomized, 65.4% in EVR+rTAC arm and 87.0% in MMF+sTAC arm completed study treatment. M12 adherence to TAC target C0 was 50% in EVR+rTAC and 51.1% in MMF+sTAC arms; 38.9% patients in EVR+rTAC arm were above TAC target C0 and 26.7% in MMF+sTAC arm were below target C0 at M12. Mean eGFR was comparable between arms (Table 1). From RND to M12, mean eGFR numerically increased in EVR+rTAC arm, whereas it decreased in MMF+sTAC arm. Rates of BPAR were comparable between arms (Table 2) with 100% renal graft and patient survival. Overall safety including renal adverse events (AE; EVR+rTAC, 15.4% vs MMF+sTAC, 18.5%) were similar between arms. AE leading to study drug discontinuation were higher in EVR+rTAC vs MMF+sTAC arm. Most patients (EVR+rTAC, 72.5% vs MMF+sTAC, 78.3%) had mildly increased urinary protein:creatinine ratio at M12. One patient in EVR+rTAC arm discontinued study treatment due to proteinuria.

 

Conclusions:

Despite poor adherence to TAC C0, EVR+rTAC and CS withdrawal regimen preserved renal function while maintaining efficacy and safety in pRTxR up to 12M post-Tx.