title: European randomised trial of dual versus triple tacrolimus-based regimens for control of acute rejection in renal allograft recipients.
abstract: Two large multicentre studies have shown superiority of tacrolimus-based immunosuppressive regimens compared with standard cyclosporine-based therapy in renal transplantation. In these studies, tacrolimus was used in a triple drug regimen of tacrolimus, corticosteroids, and azathioprine. The present study aimed to determine whether a tacrolimus-based dual regimen achieves a similar efficacy and safety profile compared with conventional triple therapy. In this prospective, open, multicentre trial, 249 patients were randomised to receive either dual therapy (n = 125) of oral tacrolimus (initial daily dose of 0.2 mg/kg) and oral prednisone or additionally, as a triple therapy (n = 124), oral azathioprine. The primary endpoint was the incidence of acute rejection at month 3. In addition, all patients were included into a follow-up evaluation at 1 year after transplantation. Both treatment groups had similar baseline characteristics. At month 3, patient survival was 97.6 % (dual) and 96.7 % (triple); graft survival was 92.7 % (dual) and 91.7 % (triple). The incidence of treated acute rejection confirmed by biopsy was 27.4 % (dual) and 24.8 % (triple); difference 2.6 %, 95 % CI [-9.4 %-12.9 %], P = 0.755. The incidence of corticosteroid-resistant rejection (biopsy-confirmed) was 9.7 % (dual) and 10.7 % (triple). The overall adverse events profile was similar; leukopenia (1.6 % vs 11.6 %, P = 0.002) was more frequent with triple therapy. Between months 4 and 12, six (dual) and eight (triple) patients had a rejection. At month 12, patient survival was 95.6 % (dual) and 93.6 % (triple); graft survival was 91.8 % (dual) and 90.7 % (triple). Tacrolimus proved to be efficacious and safe with both dual and triple low-dose regimens. The addition of azathioprine to a tacrolimus/corticosteroid-based therapy did not result in an increased efficacy.
authors.affiliation: Department of Renal Transplantation, St. George's Hospital, Black Shaw Road, London SW17 0QT, UK. renechang@compuserve.com
authors.forename: R W
authors.initials: RW
authors.lastname: Chang
authors.forename: S
authors.initials: S
authors.lastname: Snowden
authors.forename: A
authors.initials: A
authors.lastname: Palmer
authors.forename: J T
authors.initials: JT
authors.lastname: Kwan
authors.forename: M
authors.initials: M
authors.lastname: Nicholson
authors.forename: S H
authors.initials: SH
authors.lastname: Kashi
authors.forename: O N
authors.initials: ON
authors.lastname: Fernando
authors.forename: F
authors.initials: F
authors.lastname: Perner
authors.forename: G H
authors.initials: GH
authors.lastname: Neild
mesh_terms: D000208:Acute Disease; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus