Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes

Follow-up 1 year aftercessation of treatment

Tihamer Orban, Brian Bundy, Dorothy J. Becker, Linda A. DiMeglio, Stephen E. Gitelman, Robin Goland, Peter A. Gottlieb, Carla J. Greenbaum, Jennifer B. Marks, Roshanak Monzavi, Antoinette Moran, Mark Peakman, Philip Raskin, William E. Russell, Desmond Schatz, Diane K. Wherrett, Darrell M. Wilson, Jeffrey P. Krischer, Jay S. Skyler

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1069-1075
Number of pages7
JournalDiabetes Care
Volume37
Issue number4
DOIs
StatePublished - 2014

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Type 1 Diabetes Mellitus
C-Peptide
Placebos
Therapeutics
Area Under Curve
Abatacept
Meals
Research Design
Insulin
Serum

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Orban, T., Bundy, B., Becker, D. J., DiMeglio, L. A., Gitelman, S. E., Goland, R., ... Skyler, J. S. (2014). Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: Follow-up 1 year aftercessation of treatment. Diabetes Care, 37(4), 1069-1075. https://doi.org/10.2337/dc13-0604

Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes : Follow-up 1 year aftercessation of treatment. / Orban, Tihamer; Bundy, Brian; Becker, Dorothy J.; DiMeglio, Linda A.; Gitelman, Stephen E.; Goland, Robin; Gottlieb, Peter A.; Greenbaum, Carla J.; Marks, Jennifer B.; Monzavi, Roshanak; Moran, Antoinette; Peakman, Mark; Raskin, Philip; Russell, William E.; Schatz, Desmond; Wherrett, Diane K.; Wilson, Darrell M.; Krischer, Jeffrey P.; Skyler, Jay S.

In: Diabetes Care, Vol. 37, No. 4, 2014, p. 1069-1075.

Research output: Contribution to journalArticle

Orban, T, Bundy, B, Becker, DJ, DiMeglio, LA, Gitelman, SE, Goland, R, Gottlieb, PA, Greenbaum, CJ, Marks, JB, Monzavi, R, Moran, A, Peakman, M, Raskin, P, Russell, WE, Schatz, D, Wherrett, DK, Wilson, DM, Krischer, JP & Skyler, JS 2014, 'Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: Follow-up 1 year aftercessation of treatment', Diabetes Care, vol. 37, no. 4, pp. 1069-1075. https://doi.org/10.2337/dc13-0604
Orban, Tihamer ; Bundy, Brian ; Becker, Dorothy J. ; DiMeglio, Linda A. ; Gitelman, Stephen E. ; Goland, Robin ; Gottlieb, Peter A. ; Greenbaum, Carla J. ; Marks, Jennifer B. ; Monzavi, Roshanak ; Moran, Antoinette ; Peakman, Mark ; Raskin, Philip ; Russell, William E. ; Schatz, Desmond ; Wherrett, Diane K. ; Wilson, Darrell M. ; Krischer, Jeffrey P. ; Skyler, Jay S. / Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes : Follow-up 1 year aftercessation of treatment. In: Diabetes Care. 2014 ; Vol. 37, No. 4. pp. 1069-1075.
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T1 - Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes

T2 - Follow-up 1 year aftercessation of treatment

AU - Orban, Tihamer

AU - Bundy, Brian

AU - Becker, Dorothy J.

AU - DiMeglio, Linda A.

AU - Gitelman, Stephen E.

AU - Goland, Robin

AU - Gottlieb, Peter A.

AU - Greenbaum, Carla J.

AU - Marks, Jennifer B.

AU - Monzavi, Roshanak

AU - Moran, Antoinette

AU - Peakman, Mark

AU - Raskin, Philip

AU - Russell, William E.

AU - Schatz, Desmond

AU - Wherrett, Diane K.

AU - Wilson, Darrell M.

AU - Krischer, Jeffrey P.

AU - Skyler, Jay S.

PY - 2014

Y1 - 2014

N2 - 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.

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