Faculty Collaboration Database

Daclizumab to prevent rejection after cardiac transplantation. N Engl J Med 2005 Jun 30;352(26):2705-13

Date

07/01/2005

Pubmed ID

15987919

DOI

10.1056/NEJMoa032953

Scopus ID

2-s2.0-21244490121 (requires institutional sign-in at Scopus site)   185 Citations

Abstract

BACKGROUND: Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among renal-transplant recipients and, in a single-center trial, among cardiac-transplant recipients. We conducted a multicenter, placebo-controlled, double-blind study to confirm these results in cardiac-transplant patients.

METHODS: We randomly assigned 434 recipients of a first cardiac transplant treated with standard immunosuppression (cyclosporine, mycophenolate mofetil, and corticosteroids) to receive five doses of daclizumab or placebo. The primary end point was a composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up within six months.

RESULTS: By six months, 104 of 218 patients in the placebo group had reached the primary end point, as compared with 77 of the 216 patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1 percent absolute risk reduction and a 25 percent relative reduction. The rate of rejection was lower in the daclizumab group than in the placebo group (41.3 percent vs. 25.5 percent). Among patients reaching the primary end point, the median time to the end point was almost three times as long in the daclizumab group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1 year (96 vs. 26 days). More patients in the daclizumab group than in the placebo group died of infection (6 vs. 0) when they received concomitant cytolytic therapy.

CONCLUSIONS: Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplantation. Because of the excess risk of death, concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided.

Author List

Hershberger RE, Starling RC, Eisen HJ, Bergh CH, Kormos RL, Love RB, Van Bakel A, Gordon RD, Popat R, Cockey L, Mamelok RD

MESH terms used to index this publication - Major topics in bold

Adolescent
Adrenal Cortex Hormones
Adult
Aged
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Cyclosporine
Double-Blind Method
Drug Therapy, Combination
Female
Graft Rejection
Heart Transplantation
Humans
Immunoglobulin G
Immunosuppressive Agents
Logistic Models
Male
Middle Aged
Mycophenolic Acid
Opportunistic Infections
Survival Analysis