2010 - TTS International Congress


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Clinical Immunosuppression Kidney early

22.14 - Everolimus Allows For A 60% Reduction in Cyclosporine Exposure in Subject Cohorts defined by Geography

Presenter: R, Walker, Melbourne, Australia
Authors: Walker R., Cibrik D., Tedesco-Silva H., Johnston T., Kim Y., Zibari G., Cornu-Artis C., Panis C., Jiang H.

EVEROLIMUS ALLOWS FOR A 60% REDUCTION IN CYCLOSPORINE EXPOSURE IN SUBJECT COHORTS DEFINED BY GEOGRAPHY

CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

R. Walker1, D.M. Cibrik2, H. Tedesco-silva3, T. Johnston4, Y.S. Kim5, G. Zibari6, C. Cornu-artis7, C. Panis8, H. Jiang9
1, Royal Melbourne Hospital, Melbourne/AUSTRALIA, 2Internal Medicine, University of Michigan, Ann Arbor/MI/UNITED STATES OF AMERICA, 3, Hospital do Rim e Hipertensao, Sao Paulo/BRAZIL, 4, University of Kentucky Transplant Center, Lexington/AL/UNITED STATES OF AMERICA, 5Surgery, Yonsei University College of Medicine, Seoul/KOREA, 6, Willis Knighton - LSU Health Sciences Center, Shreveport/UNITED STATES OF AMERICA, 7, Novartis Pharma AG, Basel/SWITZERLAND, 8, Novartis Pharmaceuticals Corporation, East Hanover/UNITED STATES OF AMERICA, 9, Novartis Pharmaceuticals Corporation, East Hanover/NJ/UNITED STATES OF AMERICA

Body: Introduction: Demographic factors such as recipient race and donor age as well as type of donor (deceased vs. living) may influence rejection rates and renal function, post-transplantation (Tx). The A2309 study showed that everolimus (EVR) allows ~60% reduction in cyclosporine (CsA) exposure while preventing acute rejection and maintaining good renal function at 1 year post-Tx. Are these results consistent when subjects living in North American (NA) versus subjects living in South America, Europe and Asia-Pacific (nonNA) are analyzed separately? Methods: A2309, a 24 Month (M), randomized, multicenter, open-label, non-inferiority study compares 2 exposures, reduced CsA + EVR target regimens (C0 3—8ng/mL or 6—12ng/mL) vs. control (enteric-coated mycophenolate sodium [EC-MPS] 1.44g/day + standard CsA). Recipient/donor demographics, drug exposure, composite efficacy failure endpoint (treated BPAR, graft loss, death and loss to follow-up) and renal function (MDRD) were assessed in NA and nonNA cohorts. Results: Donor/recipient gender, HLA mismatches, primary kidney disease, EVR and CsA mean C0 levels and EC-MPS dosing were comparable whereas recipient/donor race and age (<50 vs. ≥50 yrs) and donor type were different (P<0.01) in the 2 cohorts. Proportion of Black and Asian patients was different with 22% and 3% vs. 7% and 20% in the NA vs. nonNA cohorts, respectively. Mean CsA C0 reduced vs. EC-MPS at 12M by 58% and 62% for EVR 3—8 ng/mL and 6—12 ng/mL, respectively (NA) vs. 61% and 66% respectively (nonNA). There was no significant treatment-by-race interaction on composite efficacy failure endpoint (P=0.495); no treatment-by-donor age or treatment-by-graft type interaction was observed (P=0.418, P=0.144) on renal function. [See Table]. Conclusions: Demographic differences were observed between the 2 cohorts and some did influence the outcomes, but in a similar way across all treatment groups. Analysis confirms that EVR with reduced CsA vs. EC-MPS with standard CsA was similarly efficacious between the cohorts and that EVR allows reduced CsA exposure at 12M by ~60% in both the cohorts.

12M endpoints EVR 3–8 ng/mL EVR 6–12 ng/mL EC-MPS 1.44 g/day
Composite efficacy failure – NA cohort# (%) 28.6 27.0 25.2
Composite efficacy failure – nonNA cohort (%) 22.8 17.0 23.4
eGFR* (ml/min/1.73m2) – NA cohort 54.4 (17.6) 55.7 (19.2) 55.8 (33.7)
eGFR (ml/min/1.73m2) – nonNA cohort 57.7 (21.8) 54.3 (20.3) 53.2 (18.8)
#% patients experiencing endpoint; *eGFR, Mean estimated Glomerular Filtration Rate (SD) – MDRD formula.

Disclosure: All authors have declared no conflicts of interest.


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