Everolimus (Certican) 12-month safety and efficacy versus mycophenolate mofetil in de novo renal transplant recipients.

Abstract

BACKGROUND:

Everolimus is a proliferation inhibitor designed to target chronic rejection, including prevention of acute rejection. Everolimus blocks growth factor-mediated transduction signals, preventing organ rejection by a mechanism different than that of calcineurin inhibitors and of mycophenolate mofetil (MMF). METHODS.: Everolimus (1.5 mg or 3 mg daily) was compared with MMF (2 g daily) in a randomized, multicenter, multinational, 12-month double-blind, double-dummy and 2-year open-label, phase 3 trial in de novo renal allograft recipients (n = 588) who also received cyclosporine and corticosteroids as part of a triple immunosuppressive regimen.

RESULTS:

At 12 months, there were no statistically significant differences between doses of 1.5 and 3 mg/day everolimus and MMF (2 g/day) in incidence of biopsy-proven acute rejection (23.2%, 19.7%, and 24.0%, respectively), graft loss (4.6%, 10.6%, and 9.2%), or death (5.2%, 4.0%, and 2.6%), respectively. Everolimus 1.5 mg/day and MMF were generally equally well tolerated. Both were better tolerated than everolimus 3 mg/day. The incidence of cytomegalovirus infection was significantly lower in patients receiving either 1.5 or 3 mg/day everolimus than in those receiving MMF (5.2% and 7.6% vs. 19.4%, respectively) (P = .001).

CONCLUSIONS:

Everolimus is effective in preventing acute rejection and graft loss in de novo renal allograft recipients receiving a triple immunosuppressive regimen. Prevention of acute rejection, along with reduction in cytomegalovirus infection, addresses two factors known to contribute to chronic rejection in such patients.

• Authors: Stefan Vítko, Raimund Margreiter, Willem Weimar, Jacques Dantal, Hendrik G Viljoen, Yulan Li, Annette Jappe, Nathalie Cretin, RAD B201 Study Group
• Journal: Transplantation (Transplantation) Vol. 78 Issue 10 Pg. 1532-40 (Nov 27 2004) ISSN: 0041-1337 [Print] United States
• PMID: 15599319 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Everolimus
• Mycophenolic Acid
• Sirolimus
• Methylprednisolone

Topics

• Adolescent
• Adult
• Aged
• Biopsy
• Dose-Response Relationship, Drug
• Double-Blind Method
• Everolimus
• Female
• Graft Rejection (drug therapy, epidemiology)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Kidney Transplantation (immunology, mortality, pathology)
• Male
• Methylprednisolone (therapeutic use)
• Middle Aged
• Mycophenolic Acid (analogs & derivatives, therapeutic use)
• Safety
• Sirolimus (analogs & derivatives, therapeutic use)
• Survival Analysis
• Treatment Outcome