Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation.
BACKGROUND
Corticosteroid-free maintenance immunosuppression after organ transplantation eliminates the well-known corticosteroid-related side effects and may help to improve long-term outcome. We investigated whether a corticosteroid-free tacrolimus (Tac)/mycophenolate mofetil (MMF) regimen, in combination with daclizumab (Dac) induction therapy, provides adequate immunosuppression after renal transplantation.


METHODS
This 6-month, open-label, multicenter, parallel-group study involved 538 renal patients randomized (1:1) to a Dac/Tac/MMF regimen (n = 260) or a Tac/MMF/corticosteroids regimen (n = 278) as a control group.


RESULTS
Of the patients who completed the study, 88.8% in the Dac/Tac/MMF group were free from corticosteroid therapy at month 6. The incidence of biopsy-proven acute rejection was 16.5% in both treatment groups; the incidence of biopsy-proven corticosteroid-resistant acute rejection was 4.3% and 5.0% with Tac/MMF/corticosteroids and Dac/Tac/MMF, respectively (P = NS for both comparisons). Renal function was also similar in both groups: median serum creatinine at month 6 was 125.0 micromol/L (Tac/MMF/corticosteroids) and 131.0 microml/L (Dac/Tac/MMF), P = 0.277. The overall safety profile was similar with both regimens. However, compared with the Tac/MMF/steroid regimen, a significantly reduced incidence of new-onset insulin-dependent diabetes mellitus (5.4% vs. 0.4%, P = 0.003) was found with steroid-free immunosuppression. Moreover, mean total cholesterol concentrations increased from baseline in the Tac/MMF/corticosteroids group by 0.19 mmol/L, whereas in the Dac/Tac/MMF group, levels decreased by 0.19 mmol/L, P = 0.005.


CONCLUSIONS
Corticosteroid-free immunosuppression with a Dac/Tac/MMF regimen is as effective at preventing acute rejection after renal transplantation as a standard triple regimen of Tac/MMF/corticosteroids. Furthermore, the safety benefits reported with Dac/Tac/MMF treatment may help improve the long-term outcome for renal-transplant patients.
Rostaing
Lionel
L
Multiorgan Transplant Unit, Rangueil University Hospital, 31059 Toulouse, France.
Cantarovich
Diego
D
Mourad
Georges
G
Budde
Klemens
K
Rigotti
Paolo
P
Mariat
Christophe
C
Margreiter
Raimund
R
Capdevilla
Luis
L
Lang
Phillippe
P
Vialtel
Paul
P
Ortuño-Mirete
Joaquin
J
Charpentier
Bernard
B
Legendre
Christophe
C
Sanchez-Plumed
Jaime
J
Oppenheimer
Federico
F
Kessler
Michele
M
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002784:Cholesterol / Q000097:blood; D000077561:Daclizumab; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology*; D019172:Transplantation Conditioning
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D002784:Cholesterol; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus