Title: Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes
Authors: Keymeulen, Bart ×
Vandemeulebroucke, Evy
Ziegler, Anette G
Mathieu, Chantal
Kaufman, Leonard
Hale, Geoff
Gorus, Frans
Goldman, Michel
Walter, Markus
Candon, Sophie
Schandene, Liliane
Crenier, Laurent
De Block, Christophe
Seigneurin, Jean-Marie
De Pauw, Pieter
Pierard, Denis
Weets, Ilse
Rebello, Peppy
Bird, Pru
Berrie, Eleanor
Frewin, Mark
Waldmann, Herman
Bach, Jean-François
Pipeleers, Daniel
Chatenoud, Lucienne #
Issue Date: Jun-2005
Series Title: The New England Journal of Medicine vol:352 issue:25 pages:2598-2608
Abstract: BACKGROUND: Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that leads to a major loss of insulin-secreting beta cells. The further decline of beta-cell function after clinical onset might be prevented by treatment with CD3 monoclonal antibodies, as suggested by the results of a phase 1 study. To provide proof of this therapeutic principle at the metabolic level, we initiated a phase 2 placebo-controlled trial with a humanized antibody, an aglycosylated human IgG1 antibody directed against CD3 (ChAglyCD3). METHODS: In a multicenter study, 80 patients with new-onset type 1 diabetes were randomly assigned to receive placebo or ChAglyCD3 for six consecutive days. Patients were followed for 18 months, during which their daily insulin needs and residual beta-cell function were assessed according to glucose-clamp-induced C-peptide release before and after the administration of glucagon. RESULTS: At 6, 12, and 18 months, residual beta-cell function was better maintained with ChAglyCD3 than with placebo. The insulin dose increased in the placebo group but not in the ChAglyCD3 group. This effect of ChAglyCD3 was most pronounced among patients with initial residual beta-cell function at or above the 50th percentile of the 80 patients. In this subgroup, the mean insulin dose at 18 months was 0.22 IU per kilogram of body weight per day with ChAglyCD3, as compared with 0.61 IU per kilogram with placebo (P<0.001). In this subgroup, 12 of 16 patients who received ChAglyCD3 (75 percent) received minimal doses of insulin (< or =0.25 IU per kilogram per day) as compared with none of the 21 patients who received placebo. Administration of ChAglyCD3 was associated with a moderate "flu-like" syndrome and transient symptoms of Epstein-Barr viral mononucleosis. CONCLUSIONS: Short-term treatment with CD3 antibody preserves residual beta-cell function for at least 18 months in patients with recent-onset type 1 diabetes.
ISSN: 0028-4793
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Residents Medicine
Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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