In the first head-to-head comparison of the two drugs most commonly given to prevent acute kidney rejection after transplant, an international study led by School of Medicine researchers shows that one of them — made from a rabbit antibody — is superior.
The results also suggest the drug could potentially save millions in health-care costs by preventing the all-out immune attacks that can eventually lead to rejection.
The study, published in the Nov. 9 issue of the New England Journal of Medicine, included only patients who were at high risk for acute rejection and for delays in graft function, in part because their kidneys came from cadaver donors. One year after transplant, 15.6 percent of patients who received anti-thymocyte globulin (brand name Thymoglobulin), a polyclonal rabbit antibody, had acute rejection, compared with 25.5 percent of patients receiving basiliximab (brand name Simulect).
Anti-thymocyte globulin was even more effective at preventing episodes of acute rejection that require additional antibody therapy to stem the immune assault. Only 1.4 percent of patients who received anti-thymocyte globulin experienced such acute rejection versus 8 percent who got basiliximab.
“Acute rejection is a major risk factor for eventually losing a kidney,” said Daniel C. Brennan, M.D., professor of medicine and director of transplant nephrology. “Our study shows that anti-thymocyte globulin is an important weapon for fighting kidney rejection. A 10 percent difference in acute rejection between the two groups may not seem like a lot, but in these high-risk patients, it is very significant.”
The study involved 278 patients in the United States and Europe who were randomly assigned to receive either anti-thymocyte globulin or basiliximab. This short-term induction therapy is given to about 70 percent of patients during kidney transplant surgery and in the first several days afterward to prevent acute rejection prior to the start of more potent, long-term immunosuppressive therapy.
The study found no significant difference between the drugs in terms of delayed graft function, or the kidney’s inability to make urine within the first week following transplant surgery. About 40 percent of patients in both groups experienced a delay in graft function. Brennan attributed this to the extended period of time the kidneys were kept on ice before transplant surgery, an average of 25 hours for patients in the anti-thymocyte group and 28 hours for the basiliximab group.
“Based on the effectiveness of anti-thymocyte globulin, we expect that it will be more effective over time in preventing graft loss and reducing patient deaths,” Brennan said.
Although anti-thymocyte globulin is more expensive than basiliximab, Brennan said he believes it will save health-care dollars in the long run.
“The cost to society for every episode of kidney rejection is extremely high,” Brennan said. “While further study is warranted, we suspect anti-thymocyte globulin will be important not only for patients at high risk for rejection but for all kidney transplant patients.”