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Previous Volume 338:1700-1701 June 4, 1998 Number 23 Next

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To the Editor: Vincenti et al. (Jan. 15 issue)¹ reported that daclizumab, a monoclonal antibody that blocks the interleukin-2 receptor, reduced the frequency of episodes of acute rejection by 37 percent during the first six months after renal transplantation in a study involving mainly U.S. centers. This result is similar to the 34 percent reduction reported in a recent European trial of a similar monoclonal antibody, basiliximab.² Surprisingly, however, the overall rates of acute rejection were considerably lower in the U.S. study than in the European study (rates in the control groups: 39 percent vs. 52 percent, P=0.02; rates in the treated groups: 25 percent vs. 34 percent, P=0.10). What could account for the lower risk of rejection in the U.S. study? First, the patients were given azathioprine, whereas the European patients were not. Second, the doses of cyclosporine and the blood cyclosporine concentrations reported in the European trial ² appear low according to U.S. standards. Unfortunately, Vincenti et al. did not provide data on cyclosporine doses or blood concentrations. This information might help clarify why the rejection rates were higher in the European renal-transplant recipients.

Daniel Abramowicz, M.D.
Hôpital Erasme
1070 Brussels, Belgium

References

1. Vincenti F, Kirkman R, Light S, et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med 1998;338:161-165. [Free Full Text]
2. Nashan B, Moore R, Amlot P, Schmidt A-G, Abeywickrama K, Soulillou J-P. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. Lancet 1997;350:1193-1198. [CrossRef][Medline]

To the Editor: The lower overall rate of rejection in our trial is most likely due to multiple factors.¹ The mean daily doses and the mean trough blood concentrations of cyclosporine in the placebo and daclizumab groups were higher than those in the basiliximab trial. Transplant recipients in the United States are more heterogeneous than in Europe; for example, 37 percent of the patients in the daclizumab trial were not white, as compared with 5 percent in the basiliximab trial. This heterogeneity has led most U.S. transplantation physicians to maintain higher trough blood cyclosporine concentrations in their patients and to give a third immunosuppressive drug (azathioprine or mycophenolate mofetil) in order to achieve effective immunosuppression.

Another factor that may affect the overall rate of rejection is the incidence of delayed graft function. In our study, 7 percent of patients required dialysis because of delayed graft function. The corresponding figure is not reported in the basiliximab trial. The most important message of both trials, however, is that inhibiting the amplification of the immune response to the allograft by blocking the interleukin-2 receptor reduces the frequency of acute rejection after renal transplantation.

The name of B. Kiberd was misspelled in the Appendix. We should have noted that Drs. Vincenti, Kirkman, Pescovitz, and Burdick have served as consultants to Hoffmann–LaRoche.

Flavio Vincenti, M.D.
University of California, San Francisco
San Francisco, CA 94143-0116

for the Daclizumab Triple Therapy Study Group

References

1. Nashan B, Moore R, Amlot P, Schmidt A-G, Abeywickrama K, Soulillou J-P. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. Lancet 1997;350:1193-1198.

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