2010 - TTS International Congress


This page contains exclusive content for the member of the following sections: TTS. Log in to view.

Clinical Immunosuppression Kidney early

22.38 - Clinically Better Renal Function With Everolimus and Very Low Tacrolimus Exposure in De novo Renal Transplant Recipients at 12 Months: The ASSET Study

Presenter: Maarten, Christiaans, Maastricht, Netherlands
Authors: Christiaans M., Hené R., Langer R., Tedesco Silva H., Cassuto E., Vilatoba M., Pascual J., Asztalos L., Burgos D., Vitko S.

CLINICALLY BETTER RENAL FUNCTION WITH EVEROLIMUS AND VERY LOW TACROLIMUS EXPOSURE IN DE NOVO RENAL TRANSPLANT RECIPIENTS AT 12 MONTHS: THE ASSET STUDY

CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

M. Christiaans1, R. Hené2, R.M. Langer3, H. Tedesco silva4, E. Cassuto5, M. Vilatoba6, J. Pascual7, L. Asztalos8, D. Burgos9, S. Vitko10
1Division Of Nephrology, Department Of Internal Medicine, Maastricht University Medical Centre, Maastricht/NETHERLANDS, 2, Universitair Medisch Centrum Utrecht, Utrecht/NETHERLANDS, 3Transplantation And Surgery, Semmelweis University, Budapest/HUNGARY, 4Division Of Nephrology, Hospital do Rim e Hipertensao, Sao Paolo/BRAZIL, 5Service De Néphrologie, Hôpital Pasteur, Nice/FRANCE, 6, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México/MEXICO, 7Dept Of Nephrology, Hospital del Mar, Barcelona/SPAIN, 8Institute Of Surgery, University of Debrecen, Debrecen/HUNGARY, 9, Hospital General Carlos Haya, Málaga/SPAIN, 10, Institute of Clinical and Experimental Medicine, Prague/CZECH REPUBLIC

Body: Introduction: Everolimus (EVR), a potent immunosuppressant allows for minimization of calcineurin inhibitor (CNI) exposure with preserved renal function (RF), while maintaining efficacy and tolerability comparable to standard CNI exposure, in renal transplant recipients (RTxR). The magnitude of CNI minimization is still under investigation, especially when EVR is combined with tacrolimus (Tac). The ASSET study, explored the efficacy and safety of two reduced Tac exposure regimens in combination with EVR in de novo RTxR. Methods: This was a phase III, 12 month (M), multicenter, open-label study. 228 RTxR were randomized (1:1) within 24h post-transplantation (Tx) to either of the two arms: EVR with low dose Tac (LTac) or EVR with very low dose Tac (VLTac) arm. All patients received basiliximab and steroids. For the first 3M all patients received EVR (1.5 mg bid, C0 3–8ng/mL) and Tac (0.1 mg/kg/day, C0 4–7 ng/mL) therapy. The LTac group continued the initial regimen unchanged whereas the VLTac group received Tac targeted to C0 1.5–3ng/mL until M12. Primary endpoint was RF at M12 assessed by calculated glomerular filtration rate (cGFR, MDRD formula). Key secondary endpoints were to compare between arms, efficacy failure (BPAR, graft loss, death, loss to follow-up) from M4–M12 and safety at 12M. Results: ITT-population of 224 RTxR (VLTac, 107; LTac, 117) had comparable baseline characteristics. During first 3M, mean Tac levels in VLTac and LTac arms were within the target range and thereafter mean levels were slightly higher in LTac arm compared to VLTac arm at M6 (5.4 vs 3.5 ng/mL) and M12 (5.5 vs 3.4 ng/mL). At M12, cGFR was higher in VLTac vs LTac arm (57.1±19.5 vs 51.7±20 mL/min/1.73m2, respectively) with difference in cGFR of +5.3 mL/min/1.73m2 (p=0.0299, one-sided at α-level 0.025). cGFR was lower in patients with BPAR events (Table). BPAR, graft loss, and death events from M4–12 were comparable in both treatment arms(1.1%, 1.1% and 1.1% vs 2.7%, 1.3% and 2.7% in LTac and VLTac, respectively). AEs at M12 were similar between two arms. Conclusion: Everolimus with very low tacrolimus had clinically better renal function with a higher calculated glomerular filtration rate of 5.34 mL/min/1.73m2 at Month 12 without compromising efficacy. The incidence of biopsy proven acute rejection after Month 4 was low in both groups. Overall the safety and tolerability of everolimus was similar in both arms and comparable to earlier studies. Table. cGFR (mL/min/1.73m2) with/without BPAR events

TREATMENT BPAR
With Without
VLTac 52.2±19 58.2±19.5
LTac 36.5±20.1 52.8±19.6


Disclosure: All authors have declared no conflicts of interest.


Important Disclaimer

By viewing the material on this site you understand and accept that:

  1. The opinions and statements expressed on this site reflect the views of the author or authors and do not necessarily reflect those of The Transplantation Society and/or its Sections.
  2. The hosting of material on The Transplantation Society site does not signify endorsement of this material by The Transplantation Society and/or its Sections.
  3. The material is solely for educational purposes for qualified health care professionals.
  4. The Transplantation Society and/or its Sections are not liable for any decision made or action taken based on the information contained in the material on this site.
  5. The information cannot be used as a substitute for professional care.
  6. The information does not represent a standard of care.
  7. No physician-patient relationship is being established.

Social

Contact

Staff Directory
+1-514-874-1717
info@tts.org

Address

The Transplantation Society
International Headquarters
740 Notre-Dame Ouest
Suite 1245
Montréal, QC, H3C 3X6
Canada