title: Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders.
abstract: Trials of immune therapies in new-onset type 1 diabetes (T1D) have shown success, but not all subjects respond, and the duration of response is limited. Our aim was to determine whether two courses of teplizumab, an Fc receptor-nonbinding anti-CD3 monoclonal antibody, reduces the decline in C-peptide levels in patients with T1D 2 years after disease onset. We also set out to identify characteristics of responders. We treated 52 subjects with new-onset T1D with teplizumab for 2 weeks at diagnosis and after 1 year in an open-label, randomized, controlled trial. In the intent to treat analysis of the primary end point, patients treated with teplizumab had a reduced decline in C-peptide at 2 years (mean -0.28 nmol/L [95% CI -0.36 to -0.20]) versus control (mean -0.46 nmol/L [95% CI -0.57 to -0.35]; P = 0.002), a 75% improvement. The most common adverse events were rash, transient upper respiratory infections, headache, and nausea. In a post hoc analysis we characterized clinical responders and found that metabolic (HbA1c and insulin use) and immunologic features distinguished this group from those who did not respond to teplizumab. We conclude that teplizumab treatment preserves insulin production and reduces the use of exogenous insulin in some patients with new-onset T1D. Metabolic and immunologic features at baseline can identify a subgroup with robust responses to immune therapy.
authors.affiliation: Department of Immunobiology and Internal Medicine, Yale University, New Haven, Connecticut.
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Gitelman
authors.forename: Mario R
authors.initials: MR
authors.lastname: Ehlers
authors.forename: Peter A
authors.initials: PA
authors.lastname: Gottlieb
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: William
authors.initials: W
authors.lastname: Hagopian
authors.forename: Karen D
authors.initials: KD
authors.lastname: Boyle
authors.forename: Lynette
authors.initials: L
authors.lastname: Keyes-Elstein
authors.forename: Sudeepta
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Deborah
authors.initials: D
authors.lastname: Phippard
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sayre
authors.forename: James
authors.initials: J
authors.lastname: McNamara
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D002096:C-Peptide / Q000378:metabolism*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D002096:C-Peptide; C502540:teplizumab