Tu119 - DREAMT: A Study of Abatacept in Recent Onset T1D to Determine Early Biomarkers of Response

Christine Bender – Benaroya Research Institute; Thomas Edwards – Benaroya Research Institute; Shuang Jia – The Medical College of Wisconsin; Mark Roethle – The Medical College of Wisconsin; Martin Hessner – The Medical College of Wisconsin; Hannah DeBerg – Benaroya Research Institute; Cate Speake – Benaroya Research Institute; Alice Long – Benaroya Research Institute

Abstract Text: Abatacept, a CTLA4Ig costimulation blockade drug, has shown promise in delaying decline in newly diagnosed Type 1 diabetes (T1D). However, there is a range of responsiveness among patients necessitating a biomarker to better select patients who may benefit. This DREAMT study includes 31 subjects treated for 3 months with intense sampling for biomarker discovery including two baseline timepoints, multiple timepoints during treatment, and 12 months following treatment. Initial results showed 21/31 positive response rate, with an average greater preservation of c-peptide than published historical data, as measured by quantitative response. However, a third of subjects displayed more rapid decline in 6 months which allows for a comparison to find biomarkers of response. Analyses showed that response did not correlate with age, duration of early disease or serum drug concentrations, leading us to explore other biological factors. We did observe modest transcriptional changes from whole blood RNA-sequencing at 12 weeks, including a decrease in follicular helper T cell and CD8 T cell exhaustion gene modules, as well as CD4 regulatory T cell modules as early as 4 weeks. We will follow up on these findings using high parameter flow cytometry to look at the immune cell changes and inflammatory profiling at earlier time points. Taken together, our data suggests that immune measures as early as 4 weeks could be used to predict response to abatacept in early onset T1D allowing for better selection of patients who could benefit from abatacept therapy.