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Russell, W.E.* ; Bundy, B.N.* ; Anderson, M.S.* ; Cooney, L.A.* ; Gitelman, S.E.* ; Goland, R.S.* ; Gottlieb, P.A.* ; Greenbaum, C.J.* ; Haller, M.J.* ; Krischer, J.P.* ; Libman, I.M.* ; Linsley, P.S.* ; Long, S.A.* ; Lord, S.M.* ; Moore, D.J.* ; Moore, W.V.* ; Moran, A.M.* ; Muir, A.B.* ; Raskin, P.* ; Skyler, J.S.* ; Wentworth, J.M.* ; Wherrett, D.K.* ; Wilson, D.M.* ; Ziegler, A.-G. ; Herold, K.C.*

Abatacept for delay of type 1 diabetes progression in stage 1 relatives at risk: A randomized, double-masked, controlled trial.

Diabetes Care 46, 1005-1013 (2023)
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OBJECTIVE: Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses. RESEARCH DESIGN AND METHODS: We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests. RESULTS: A total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline. CONCLUSIONS: Although abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Quellenangaben Volume: 46, Issue: 5, Pages: 1005-1013 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, Va.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)