PMID- 24296850 OWN - NLM STAT- MEDLINE DCOM- 20150122 LR - 20221207 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 37 IP - 4 DP - 2014 Apr TI - Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment. PG - 1069-75 LID - 10.2337/dc13-0604 [doi] AB - OBJECTIVE We previously reported that 2 years of costimulation modulation with abatacept slowed decline of beta-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 beta-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. FAU - Orban, Tihamer AU - Orban T AD - Corresponding author: Jay S. Skyler, jskyler@miami.edu. FAU - Bundy, Brian AU - Bundy B FAU - Becker, Dorothy J AU - Becker DJ FAU - Dimeglio, Linda A AU - Dimeglio LA FAU - Gitelman, Stephen E AU - Gitelman SE FAU - Goland, Robin AU - Goland R FAU - Gottlieb, Peter A AU - Gottlieb PA FAU - Greenbaum, Carla J AU - Greenbaum CJ FAU - Marks, Jennifer B AU - Marks JB FAU - Monzavi, Roshanak AU - Monzavi R FAU - Moran, Antoinette AU - Moran A FAU - Peakman, Mark AU - Peakman M FAU - Raskin, Philip AU - Raskin P FAU - Russell, William E AU - Russell WE FAU - Schatz, Desmond AU - Schatz D FAU - Wherrett, Diane K AU - Wherrett DK FAU - Wilson, Darrell M AU - Wilson DM FAU - Krischer, Jeffrey P AU - Krischer JP FAU - Skyler, Jay S AU - Skyler JS CN - Type 1 Diabetes TrialNet Abatacept Study Group LA - eng GR - UL1 RR024139/RR/NCRR NIH HHS/United States GR - U01-DK-084565/DK/NIDDK NIH HHS/United States GR - UL1-RR-024139/RR/NCRR NIH HHS/United States GR - UL1-RR-024153/RR/NCRR NIH HHS/United States GR - U01-DK-061042/DK/NIDDK NIH HHS/United States GR - U01 DK061036/DK/NIDDK NIH HHS/United States GR - UL1 RR024982/RR/NCRR NIH HHS/United States GR - U01 DK061042/DK/NIDDK NIH HHS/United States GR - U01 DK061041/DK/NIDDK NIH HHS/United States GR - U01 DK085476/DK/NIDDK NIH HHS/United States GR - UL1-RR-024975/RR/NCRR NIH HHS/United States GR - M01 RR000400/RR/NCRR NIH HHS/United States GR - UL1 TR000005/TR/NCATS NIH HHS/United States GR - U01 DK061010/DK/NIDDK NIH HHS/United States GR - UL1 RR025761/RR/NCRR NIH HHS/United States GR - P30 DK063720/DK/NIDDK NIH HHS/United States GR - U01 DK061040/DK/NIDDK NIH HHS/United States GR - UL1 RR024153/RR/NCRR NIH HHS/United States GR - UL1 RR029890/RR/NCRR NIH HHS/United States GR - UL1 TR001105/TR/NCATS NIH HHS/United States GR - UL1 RR031986/RR/NCRR NIH HHS/United States GR - U01 DK085466/DK/NIDDK NIH HHS/United States GR - MR/J006742/1/MRC_/Medical Research Council/United Kingdom GR - U01-DK-085509/DK/NIDDK NIH HHS/United States GR - U01 DK061058/DK/NIDDK NIH HHS/United States GR - U01 DK085505/DK/NIDDK NIH HHS/United States GR - U01 DK085453/DK/NIDDK NIH HHS/United States GR - UL1 RR025780/RR/NCRR NIH HHS/United States GR - U01-DK-061036/DK/NIDDK NIH HHS/United States GR - U01-DK-061041/DK/NIDDK NIH HHS/United States GR - U01-DK-085463/DK/NIDDK NIH HHS/United States GR - U01-DK-085466/DK/NIDDK NIH HHS/United States GR - UL1-RR-031986/RR/NCRR NIH HHS/United States GR - UL1 RR024131/RR/NCRR NIH HHS/United States GR - DP3 DK097681/DK/NIDDK NIH HHS/United States GR - U01 DK085499/DK/NIDDK NIH HHS/United States GR - UL1 TR000093/TR/NCATS NIH HHS/United States GR - U01 DK085463/DK/NIDDK NIH HHS/United States GR - UL1 TR001108/TR/NCATS NIH HHS/United States GR - U01-DK-085505/DK/NIDDK NIH HHS/United States GR - U01 DK061055/DK/NIDDK NIH HHS/United States GR - UL1 RR025744/RR/NCRR NIH HHS/United States GR - HHSN267200800019C/DK/NIDDK NIH HHS/United States GR - U01-DK-061055/DK/NIDDK NIH HHS/United States GR - UL1 TR001085/TR/NCATS NIH HHS/United States GR - UL1-RR-025744/RR/NCRR NIH HHS/United States GR - U01 DK061034/DK/NIDDK NIH HHS/United States GR - UL1-RR-025780/RR/NCRR NIH HHS/United States GR - UL1-RR-024982/RR/NCRR NIH HHS/United States GR - UL1 TR001082/TR/NCATS NIH HHS/United States GR - U01 DK085461/DK/NIDDK NIH HHS/United States GR - U01-DK-061058/DK/NIDDK NIH HHS/United States GR - U01 DK085509/DK/NIDDK NIH HHS/United States GR - UL1 RR024975/RR/NCRR NIH HHS/United States GR - UL1-RR-025761/RR/NCRR NIH HHS/United States GR - UL1-RR-029890/RR/NCRR NIH HHS/United States GR - UC4 DK117009/DK/NIDDK NIH HHS/United States GR - U01-DK-085461/DK/NIDDK NIH HHS/United States GR - UL1 TR000004/TR/NCATS NIH HHS/United States GR - U01-DK-061034/DK/NIDDK NIH HHS/United States GR - U01-DK-061040/DK/NIDDK NIH HHS/United States GR - UL1-RR-024131/RR/NCRR NIH HHS/United States GR - U01-DK-061010/DK/NIDDK NIH HHS/United States GR - UC4 DK097835/DK/NIDDK NIH HHS/United States GR - M01-RR-00400/RR/NCRR NIH HHS/United States GR - U01-DK-085453/DK/NIDDK NIH HHS/United States GR - U01-DK-061016/DK/NIDDK NIH HHS/United States GR - U01-DK-085499/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131202 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (C-Peptide) RN - 0 (Glycated Hemoglobin A) RN - 0 (Immunoconjugates) RN - 0 (Immunosuppressive Agents) RN - 0 (Placebos) RN - 0 (hemoglobin A1c protein, human) RN - 7D0YB67S97 (Abatacept) SB - IM MH - Abatacept MH - Adolescent MH - Adult MH - C-Peptide/blood MH - Child MH - Diabetes Mellitus, Type 1/*drug therapy MH - Female MH - Follow-Up Studies MH - Glycated Hemoglobin/metabolism MH - Humans MH - Immunoconjugates/*therapeutic use MH - Immunosuppressive Agents/*therapeutic use MH - Male MH - Placebos MH - *Withholding Treatment MH - Young Adult PMC - PMC3964491 EDAT- 2013/12/04 06:00 MHDA- 2015/01/23 06:00 PMCR- 2015/04/01 CRDT- 2013/12/04 06:00 PHST- 2013/12/04 06:00 [entrez] PHST- 2013/12/04 06:00 [pubmed] PHST- 2015/01/23 06:00 [medline] PHST- 2015/04/01 00:00 [pmc-release] AID - dc13-0604 [pii] AID - 0604 [pii] AID - 10.2337/dc13-0604 [doi] PST - ppublish SO - Diabetes Care. 2014 Apr;37(4):1069-75. doi: 10.2337/dc13-0604. Epub 2013 Dec 2.