“These findings are important because avoiding acute rejection helps patients keep the graft longer and live longer,” says the study’s principal investigator Daniel C.Brennan, M.D., associate professor of medicine and director of transplant nephrology at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, which has one of the lowest rates of kidney transplant rejection in the world.
Brennan will present the findings at 2:40 p.m. April 29, 2002, at the American Transplant Congress (ATC) meeting in Washington, D.C.
According to Brennan, there are about 50,800 people waiting for kidney transplants in the United States. About half of transplanted kidneys in the United States come from cadavers. Twenty to 60 percent of kidney transplant recipients will experience an acute rejection episode, an immune reaction to the transplanted organ that most often occurs in the first six months following transplantation and can cause fever, tissue destruction and loss of the transplanted kidney.
Physicians use drugs before or during surgery to prevent rejection, a method known as induction therapy. The international team found that patients receiving the drug Thymoglobulin (anti-thymocyte globlulin) had two and half times fewer episodes of acute kidney rejection than did patients receiving the leading induction therapy drug, Simulect (basiliximab). Though the two drugs showed no significant difference in safety or side effects, the greater effectiveness of Thymoglobulin caused an independent monitoring committee to halt the investigation halfway through the study.
“The interim analysis required that the data and safety monitoring board consider the ethical implications of continuing to enroll patients in a study where their risk of acute rejection could be so much greater in one treatment arm,” says Brennan. “The board concluded that closing the study early was the most appropriate course of action.”
The study’s interim findings are based on the outcomes of 212 patients (average age 49) who received kidneys from cadavers at 16 centers in the United States and 10 in Europe. Of these, 106 received Thymoglobulin and 106 received Simulect. The patients were followed an average of 6.9 months; originally, patients were to be followed for an average of 12 months.
Of the patients receiving Thymoglobulin, 8 (8 percent) had an episode of acute rejection within the follow-up period compared to 20 (19 percent) of those receiving Simulect.
Side effects associated with the two drugs were similar. Side effects following transplantation are categorized as adverse events, serious adverse events, reactivation of latent viral infections and cancer.
The percentage of adverse events in the Thymoglobulin and Simulect groups were 59 percent and 64 percent respectively; serious adverse events requiring hospitalization occurred in 32 percent and 39 percent of patients, respectively. Infectious disease occurrence, such as activation of a latent cytomegalovirus infection, was low and relatively equivalent in the two groups (Thymoglobulin 3% and Simulect 7%), as was overall graft loss (Thymoglobulin 6% and Simulect 8%). Two deaths occurred in each group.
Three cases of cancer – two lymphomas and one skin cancer – occurred in the Thymoglobulin group during the follow-up period; none developed in the Simulect group. However, the rate of lymphoma is 1 percent to 2 percent in the general population, and 1 percent to 5 percent in kidney transplant patients, says Brennan, so this result was not surprising. According to Brennan, all three patients have been treated and are doing well.
“Based on our results, I expect that up to half of kidney transplants that come from cadavers could benefit from Thymoglobulin therapy,” Brennan says.
The study was funded by SangStat Medical Corporation, manufacturer of Thymoglobulin.
Editor’s Note: While Dr. Brennan has received grant and research support and has served as a paid consultant to SangStat Medical Corp. and Novartis, maker of Simulect, he owns no stock in either company.
Brennan DC. A prospective randomized multicenter comparison of Thymoglobulin versus Simulect for induction therapy in high-risk renal transplant recipients. American Transplant Congress, Washington, D.C., April 29, 2002.
The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.