Everolimus versus azathioprine in a cyclosporine and ketoconazole-based immunosuppressive therapy in kidney transplant: 3-year follow-up of an open-label, prospective, cohort, comparative clinical trial.
In cyclosporine-based protocols, everolimus is more effective than azathioprine to reduce acute rejection. Ketoconazole may reduce cyclosporine and everolimus requirements. We compared kidney transplant patients treated with everolimus or azathioprine in a ketoconazole- and cyclosporine-based immunosuppressive regimen. This open-label, prospective trial of low immunologic risk patients. Included one group (n = 11) who received everolimus (target blood level, 3-8 ng/mL) and the other (n = 11) azathioprine (2.0-2.5 mg/kg/d). Both received steroids, ketoconazole, and cyclosporine with C(0) targets (ng/mL) in the everolimus group of 200-250, 100-125, and 50-65 for months 1 and 2 and thereafter and in the azathioprine group of 250-300 in month 1, 200-250 in month 2, 180-200 until month 6, and 100-125 thereafter. Their baseline characteristics were similar. Two biopsy-proven acute rejections occurred in each group. Three-year graft and patient survival in both groups was 100%. Creatinine clearances at months 6, 12, 24, and 36 were 63.7 +/- 25.4, 58.9 +/- 24.9, 56.0 +/- 22.9, and 57.0 +/- 27.6 in the everolimus group versus 72.6 +/- 20, 68.6 +/- 21.3, 71.4 +/- 23.2, and 68.4 +/- 19.2 in the azathioprine group (NS for every comparison). Major complications were rare and similar in both groups. Five patients in the everolimus group received simvastatin versus 4 in the azathioprine cohort (P = .53). The average cyclosporine doses to achieve targets were 0.8-1.2 mg/kg in the everolimus group and 1.6-2.2 mg/kg in the azathioprine group. The average everolimus dose after month 2 was 0.75-0.9 mg/d. We concluded that with cyclosporine, ketoconazole, and steroids, everolimus was as effective and safe as azathioprine. Cyclosporine reduction with everolimus did not influence graft survival or function at 3 years.
Gonzalez
F
F
Faculty of Medicine, Universidad de Chile, Santiago, Chile. fgonzalf@uc.cl
Espinoza
M
M
Herrera
P
P
Rocca
X
X
Reynolds
E
E
Lorca
E
E
Roessler
E
E
Hidalgo
J
J
Espinoza
O
O
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D015234:HLA-A Antigens / Q000097:blood; D015235:HLA-B Antigens / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007654:Ketoconazole / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D000305:Adrenal Cortex Hormones; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007166:Immunosuppressive Agents; D014280:Triglycerides; D016572:Cyclosporine; D002784:Cholesterol; D000068338:Everolimus; D003404:Creatinine; D001379:Azathioprine; D007654:Ketoconazole; D020123:Sirolimus; D008775:Methylprednisolone