European randomised trial of dual versus triple tacrolimus‐based regimens for control of acute rejection in renal allograft recipients

• Published in: Transplant international 2001-12, Vol.14 (6), p.384-390
• Main Authors: Chang, R.W.S., Snowden, S., Palmer, A., Kwan, J.T.C., Nicholson, M., Kashi, S.H., Fernando, O.N., Perner, F., Neild, G.H.
• Format: Article
• Language: English
• Subjects: Acute Disease; Acute rejection; Biological and medical sciences; Female; Follow-Up Studies; Graft Rejection - prevention & control; Graft Survival; Humans; Immunomodulators; Immunosuppression; Immunosuppressive Agents - therapeutic use; Kidney transplantation; Kidney Transplantation - mortality; Male; Medical sciences; Pharmacology. Drug treatments; Tacrolimus; Tacrolimus - adverse effects; Tacrolimus - therapeutic use; Transplantation, Homologous
• ISSN: 0934-0874; 1432-2277
• DOI: 10.1111/j.1432-2277.2001.tb00076.x

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 ta‐crolimus/corticosteroid‐based therapy did not result in an increased efficacy.