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

22.23 - Dose Related Incidences of Wound Healing Events in Renal Transplant Recipients Treated With Everolimus and Cyclosporine

Presenter: Anantharaman, Vathsala, Singapore, Singapore
Authors: Vathsala A., Zibari G., Kim Y., Cibrik D., Johnston T., Walker R., Mange K., Panis C., Wang Z., Tedesco-Silva H.

DOSE RELATED INCIDENCES OF WOUND HEALING EVENTS IN RENAL TRANSPLANT RECIPIENTS TREATED WITH EVEROLIMUS AND CYCLOSPORINE

CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

A. Vathsala1, G. Zibari2, Y.S. Kim3, D. Cibrik4, T. Johnston5, R. Walker6, K. Mange7, C. Panis7, Z. Wang7, H. Tedesco-silva8
1, Singapore General Hospital, Singapore/SINGAPORE, 2, Willis Knighton - LSU Health Sciences Center, Shreveport/UNITED STATES OF AMERICA, 3, Yonsei University College of Medicine, Seoul/KOREA, 4, University of Michigan, Ann Arbor/MI/UNITED STATES OF AMERICA, 5, University of Kentucky Transplant Center, Lexington/AL/UNITED STATES OF AMERICA, 6, Royal Melbourne Hospital, Melbourne/AUSTRALIA, 7, Novartis Pharmaceuticals Corporation, East Hanover/UNITED STATES OF AMERICA, 8, Hospital do Rim e Hipertensao, Sao Paulo/BRAZIL

Body: Introduction: In renal transplant recipients (RTs), everolimus (EVR) has displayed comparable efficacy to mycophenolic acid (MPA) in the prevention of acute rejection when used with steroids and standard dose cyclosporine (sdCsA). EVR also allows for CsA dose reduction without loss of efficacy when compared with sdCsA regimens. However, the mTOR class has been associated with complications involving wound healing events (WHE) and tissue regeneration in RTs. This study compared effects of 2 dose regimens of EVR with reduced dose CsA (rdCsA) versus a control group receiving MPA with sdCsA on WHE. Methods: A2309 is a 24-month (M), randomized, multi-center, open-label, non-inferiority study comparing 2 regimens of EVR (targeting C0 either at 3–8 ng/mL or 6–12 ng/mL) with rdCsA versus a control group receiving MPA (1.44g/day) with sdCsA. All patients received basiliximab induction and steroids, given according to local practice guidelines. CsA C0 target ranges for the EVR groups were 100–200ng/mL from Day 5, 75–150ng/mL from 2M, 50–100ng/mL from 4M and 25–50ng/mL from 6M. CsA target ranges for the MPA group were 200–300ng/ml from Day 5 and 100–250ng/mL from 2M. Approximately 60% reduction in CsA exposure for both EVR regimens was achieved at 12M versus MPA control group. Primary composite endpoint was non-inferiority of efficacy (Biopsy proven acute rejection (BPAR), graft loss, death, loss to follow-up) between the EVR groups and the MPA control at 12M. Results: Donor and recipient characteristics were comparable between groups. Both the EVR groups were statistically non-inferior to the MPA control group for primary composite efficacy and renal function at 12M. Safety profiles of each regimen were consistent with findings from previous studies. Wound Healing Events as N(%)

EVR 3–8ng/mL EVR 6–12ng/mL MPA 1.44g/day
N=274 N=278 N=273
Total WHEs* 84(30.6) 96(34.5) 67(20.8)
Vascular lymphocele 18(6.7) 31(11.2) 14(5.1)
Impaired healing 5(1.8) 11(4.0) 3(1.1)
Wound dehiscence 4(1.5) 9(3.2) 4(1.5)
WHE listed as serious AE 17(6.3) 22(8.0) 11(4.2)
Discontinued due to WHE 4(1.5) 7(2.5) 0(0)
WHEs needing surgical intervention 29(10.6) 35(12.6) 18(6.6)

*Total Wound Healing Events (WHEs) excludes infections and infestations Onset of WHEs for all 3 groups was within 5–75 days post-transplantation and over 50% of WHEs were <45 days in duration. For the EVR 3–8ng/ml and 6–12ng/ml groups, WHE reported in patients with a body mass index (BMI) greater than the 75th percentile were 50% and 46% respectively (versus 27% for the MPA group). EVR levels appear to be related to increased incidence of wound healing delays (>= 45days vs. <56 days). Overall, no significant difference was observed between the EVR 3–8ng/ml and MPA groups. Conclusions: Wound healing events occurred predominantly in the early de novo period. An EVR C0 concentration-response relationship was observed for the incidence of wound healing events with consistently lower events in the EVR 3–8ng/ml target range. Patients with a higher BMI who receive EVR may be at higher risk for these events as supported in other studies.

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