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.
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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)
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Chemical References |
- Immunosuppressive Agents
- Everolimus
- Mycophenolic Acid
- Sirolimus
- Methylprednisolone
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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
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