Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb teplizumab preserves insulin production for up to 5 years

Abstract Anti-CD3 mAbs may prolong β cell function up to 2 years in patients with new onset Type 1 diabetes (T1DM). A randomized open label trial of anti-CD3 mAb, Teplizumab, in T1DM was stopped after 10 subjects because of increased adverse events than in a previous trial related with higher dosing...

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Published in:Clinical immunology (Orlando, Fla.) Fla.), 2009-08, Vol.132 (2), p.166-173
Main Authors: Herold, Kevan C, Gitelman, Stephen, Greenbaum, Carla, Puck, Jennifer, Hagopian, William, Gottlieb, Peter, Sayre, Peter, Bianchine, Peter, Wong, Emelita, Seyfert-Margolis, Vicki, Bourcier, Kasia, Bluestone, Jeffrey A
Format: Article
Language:English
Subjects:
Adolescent
Allergy and Immunology
Anti-CD3 monoclonal antibody
Antibodies, Monoclonal, Humanized
Biological and medical sciences
C-Peptide - metabolism
CD3 Complex - immunology
Child
Diabetes Mellitus, Type 1 - drug therapy
Diabetes Mellitus, Type 1 - metabolism
Diabetes Mellitus, Type 1 - pathology
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Exanthema - chemically induced
Female
Fever - chemically induced
Follow-Up Studies
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gastrointestinal Diseases - chemically induced
Humans
Hypoglycemic Agents - metabolism
Hypoglycemic Agents - therapeutic use
Immunotherapy
Insulin - metabolism
Insulin - therapeutic use
Male
Medical sciences
Muromonab-CD3 - adverse effects
Muromonab-CD3 - therapeutic use
Nausea - chemically induced
T lymphocyte
Treatment Outcome
Type 1 diabetes mellitus
Vomiting - chemically induced
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Summary:Abstract Anti-CD3 mAbs may prolong β cell function up to 2 years in patients with new onset Type 1 diabetes (T1DM). A randomized open label trial of anti-CD3 mAb, Teplizumab, in T1DM was stopped after 10 subjects because of increased adverse events than in a previous trial related with higher dosing of drug. Teplizumab caused transient reduction in circulating T cells, but the recovered cells were not new thymic emigrants because T cell receptor excision circles were not increased. There was a trend for reduced loss of C-peptide over 2 years with drug treatment ( p = 0.1), and insulin use was lower ( p < 0.001). In 4 drug-treated subjects followed up to 60 months, C-peptide responses were maintained. We conclude that increased doses of Teplizumab are associated with greater adverse events without improved efficacy. The drug may marginate rather than deplete T cells. C-peptide levels may remain detectable up to 5 years after treatment.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2009.04.007