Baseline insulin secretion determines the response to abatacept in Stage 1 type 1 diabetes

Résumé fourni par la source

Abatacept, a CTLA-4 immunoglobulin that inhibits T cell costimulation, was evaluated for 12 months in Stage 1 type 1 diabetes to delay disease progression. Despite modest preservation of AUC C-peptide at 12 months, the primary endpoint was not met. Herein, we adopt the oral minimal model (OMM) to assess beta cell function over 48 months and explore how baseline insulin secretion (Phitot) modifies treatment response. Phitot was computed using the OMM from the oral glucose tolerance test at baseline and every 6 months. Participants were stratified into high- or low-secretors depending on baseline Phitot 33rd or <33rd centile, respectively. A sensitivity analysis was performed to validate threshold choice. Among 203 participants (96 abatacept and 107 placebo), 39% on abatacept and 47% on placebo progressed to Stage 2 or 3 within 96 months. High-secretors on abatacept gained 15.8 progression-free months ([95%CI 4.85, 26.68] p=0.005) and had 54% lower hazard of progression vs placebo (HR 0.46 [95%CI 0.25, 0.84] p=0.012). Treatment effect differed significantly by secretor status (interaction HR 2.92[95%CI 1.23, 6.96] p=0.015). Phitot identifies a responder subgroup to 12-months of abatacept, with delayed disease progression, providing the first evidence that an immune intervention in Stage 1 may delay disease progression.

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