Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation

Flavio Vincenti, Robert Kirkman, Susan Light, Ginny Bumgardner, Mark Pescovitz, Philip Halloran, John Neylan, Alan Wilkinson, Henrik Ekberg, Robert Gaston, Lars Backman, James F. Burdick

Research output: Contribution to journalArticle

Abstract

Background: Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the a chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation. Methods: We administered daclizumab (1.0 mg per kilogram of body weight) or placebo intravenously before transplantation and once every other week afterward, for a total of five doses, to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine, azathioprine, and prednisone. The patients were followed at regular intervals for 12 months. The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation. Results: Of the 126 patients given daclizumab, 28 (22 percent) had biopsy- confirmed episodes of acute rejection, as compared with 47 of the 134 patients (35 percent) who received placebo (P=0.03). Graft survival at 12 months was 95 percent in the daclizumab-treated patients, as compared with 90 percent in the patients given placebo (P=0.08). The patients given daclizumab did not have any adverse reactions to the drug, and at six months, there were no significant differences between the two groups with respect to infectious complications or cancers. The serum half-life of daclizumab was 20 days, and its administration resulted in prolonged saturation of interleukin-2α receptors on circulating lymphocytes. Conclusions: Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients.

Original languageEnglish (US)
Pages (from-to)161-165
Number of pages5
JournalNew England Journal of Medicine
Volume338
Issue number3
DOIs
StatePublished - Jan 15 1998

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Interleukin-2 Receptors
Kidney Transplantation
Placebos
Transplantation
Monoclonal Antibodies
Kidney
Biopsy
Isoantigens
Azathioprine
Graft Survival
Immunosuppressive Agents
Prednisone
daclizumab
Drug-Related Side Effects and Adverse Reactions
Immunosuppression
Cyclosporine
Half-Life
Immunoglobulin G
Body Weight
Lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

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Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. / Vincenti, Flavio; Kirkman, Robert; Light, Susan; Bumgardner, Ginny; Pescovitz, Mark; Halloran, Philip; Neylan, John; Wilkinson, Alan; Ekberg, Henrik; Gaston, Robert; Backman, Lars; Burdick, James F.

In: New England Journal of Medicine, Vol. 338, No. 3, 15.01.1998, p. 161-165.

Research output: Contribution to journalArticle

Vincenti, F, Kirkman, R, Light, S, Bumgardner, G, Pescovitz, M, Halloran, P, Neylan, J, Wilkinson, A, Ekberg, H, Gaston, R, Backman, L & Burdick, JF 1998, 'Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation', New England Journal of Medicine, vol. 338, no. 3, pp. 161-165. https://doi.org/10.1056/NEJM199801153380304
Vincenti, Flavio ; Kirkman, Robert ; Light, Susan ; Bumgardner, Ginny ; Pescovitz, Mark ; Halloran, Philip ; Neylan, John ; Wilkinson, Alan ; Ekberg, Henrik ; Gaston, Robert ; Backman, Lars ; Burdick, James F. / Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. In: New England Journal of Medicine. 1998 ; Vol. 338, No. 3. pp. 161-165.
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AU - Pescovitz, Mark

AU - Halloran, Philip

AU - Neylan, John

AU - Wilkinson, Alan

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AU - Burdick, James F.

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