title: 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 beta 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.
authors.affiliation: Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.forename: Stephen
authors.initials: S
authors.lastname: Gitelman
authors.forename: Carla
authors.initials: C
authors.lastname: Greenbaum
authors.forename: Jennifer
authors.initials: J
authors.lastname: Puck
authors.forename: William
authors.initials: W
authors.lastname: Hagopian
authors.forename: Peter
authors.initials: P
authors.lastname: Gottlieb
authors.forename: Peter
authors.initials: P
authors.lastname: Sayre
authors.forename: Peter
authors.initials: P
authors.lastname: Bianchine
authors.forename: Emelita
authors.initials: E
authors.lastname: Wong
authors.forename: Vicki
authors.initials: V
authors.lastname: Seyfert-Margolis
authors.forename: Kasia
authors.initials: K
authors.lastname: Bourcier
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized; D002096:C-Peptide / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D016853:Muromonab-CD3 / Q000009:adverse effects / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D002096:C-Peptide; D017252:CD3 Complex; D007004:Hypoglycemic Agents; D007328:Insulin; D016853:Muromonab-CD3; C502540:teplizumab