title: Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment.
abstract: OBJECTIVE We previously reported that 2 years of costimulation modulation with abatacept slowed decline of β-cell function in recent-onset type 1 diabetes (T1D). Subsequently, abatacept was discontinued and subjects were followed to determine whether there was persistence of effect. RESEARCH DESIGN AND METHODS Of 112 subjects (ages 6-36 years) with T1D, 77 received abatacept and 35 received placebo infusions intravenously for 27 infusions over 2 years. The primary outcome-baseline-adjusted geometric mean 2-h area under the curve (AUC) serum C-peptide during a mixed-meal tolerance test (MMTT) at 2 years-showed higher C-peptide with abatacept versus placebo. Subjects were followed an additional year, off treatment, with MMTTs performed at 30 and 36 months. RESULTS C-peptide AUC means, adjusted for age and baseline C-peptide, at 36 months were 0.217 nmol/L (95% CI 0.168-0.268) and 0.141 nmol/L (95% CI 0.071-0.215) for abatacept and placebo groups, respectively (P = 0.046). The C-peptide decline from baseline remained parallel with an estimated 9.5 months' delay with abatacept. Moreover, HbA1c levels remained lower in the abatacept group than in the placebo group. The slightly lower (nonsignificant) mean total insulin dose among the abatacept group reported at 2 years was the same as the placebo group by 3 years. CONCLUSIONS Costimulation modulation with abatacept slowed decline of β-cell function and improved HbA1c in recent-onset T1D. The beneficial effect was sustained for at least 1 year after cessation of abatacept infusions or 3 years from T1D diagnosis.
authors.affiliation: Corresponding author: Jay S. Skyler, jskyler@miami.edu.
authors.forename: Tihamer
authors.initials: T
authors.lastname: Orban
authors.forename: Brian
authors.initials: B
authors.lastname: Bundy
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Becker
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dimeglio
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Gitelman
authors.forename: Robin
authors.initials: R
authors.lastname: Goland
authors.forename: Peter A
authors.initials: PA
authors.lastname: Gottlieb
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Marks
authors.forename: Roshanak
authors.initials: R
authors.lastname: Monzavi
authors.forename: Antoinette
authors.initials: A
authors.lastname: Moran
authors.forename: Mark
authors.initials: M
authors.lastname: Peakman
authors.forename: Philip
authors.initials: P
authors.lastname: Raskin
authors.forename: William E
authors.initials: WE
authors.lastname: Russell
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
authors.forename: Diane K
authors.initials: DK
authors.lastname: Wherrett
authors.forename: Darrell M
authors.initials: DM
authors.lastname: Wilson
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D010919:Placebos; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D000069594:Abatacept; D002096:C-Peptide; D006442:Glycated Hemoglobin; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D010919:Placebos; C517652:hemoglobin A1c protein, human