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Immunosuppression: Now we have choices
Author(s) -
Sher Linda S.,
Makowka Leonard
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840220343
Subject(s) - tacrolimus , medicine , immunosuppression , corticosteroid , liver transplantation , confidence interval , gastroenterology , transplantation , refractory (planetary science) , incidence (geometry) , randomized controlled trial , ciclosporin , surgery , biology , physics , astrobiology , optics
Background . Tacrolimus (FK 506), a macrolide compound isolated from a bacterium, is a potent immuno‐suppressant with activity in solid‐organ transplants. Most immunosuppressive regimens for liver transplantation are based on cyclosporine. Methods . We conducted an open‐label, randomized, multicenter trial to compare the efficacy and safety of tacrolimus‐based and cyclosporine‐based immunosuppressive regimens for patients receiving a first liver transplant. A total of 478 adults and 51 children (⩽12 years of age) were randomly assigned at the time of transplantation to receive tacrolimus (n = 263) or cyclosporine (n = 266) and were followed for one year. The primary end points were patient and graft survival at one year. The secondary end points were the incidence of acute rejection, corticosteroid‐resistant rejection, and refractory rejection (continued rejection after two courses of corticosteroids and an intervening course of muromonab‐CD3). Results . According to Kaplan‐Meier analysis, actuarial patient‐survival rates at day 360 were 88 percent for both the tacrolimus and cyclosporine groups ( P = 0.85; 95 percent confidence interval for the difference, −5.4 to 6.6 percent), and graft‐survival rates were 82 percent and 79 percent, respectively ( P = 0.55; 95 percent confidence interval for the difference, −4.8 to 9.7 percent). Acute rejection occurred in 154 patients in the tacrolimus group and 173 patients in the cyclosporine group ( P <0.002), corticosteroid‐resistant rejection occurred in 43 and 82 patients, respectively ( P <0.001), and refractory rejection occurred in 6 and 32 patients, respectively ( P <0.001). Tacrolimus was associated with a higher incidence of adverse events requiring withdrawal from the study, primarily nephrotoxicity and neurotoxicity; 37 patients in the tacrolimus group and 13 in the cyclosporine group discontinued the study because of adverse events ( P <0.001). Conclusions . After one year, immunosuppressive regimens based on tacrolimus and cyclosporine were comparable in terms of patient and graft survival. Tacrolimus was associated with significantly fewer episodes of acute, corticosteroid‐resistant, or refractory rejection, but substantially more adverse events requiring discontinuation of the drug. (N Engl J Med 1994;331:1110–1115.)