114-OR: A Randomized Clinical Trial of Etanercept and Alpha-1 Antitrypsin in TPIAT

Abstract

Total pancreatectomy with islet auto-transplant (TPIAT) can relieve pain for patients with intractable pancreatitis. However, inflammatory damage to transplanted islets from the instant blood mediated inflammatory response (IBMIR) limits the IAT's success. We hypothesized blockade of IBMIR would improve islet engraftment, resulting in improved islet function. We randomized 43 participants to A1AT (90 mg/kg IV x6 doses) , or etanercept (50 mg then 25 mg SQ x 5 doses) , or standard care in a 1:1:1 ratio. Islet graft function was assessed with mixed meal tolerance test (MMTT) , intravenous glucose tolerance test (IVGTT) , glucose-potentiated arginine-induced insulin secretion (GPAIS) , HbA1c, and insulin use 3 months and 1 year after TPIAT. Acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) 3 months after TPIAT were higher in the etanercept-treated group (p<0.025, Fig 1) , but neither treatment differed significantly from controls at 1 year (Fig 1) . MMTT, GPAIS, HbA1c, and insulin use did not differ between groups. Multivariate modelling suggested a sex-specific response, with females on A1AT showing the most robust insulin secretion from GPAIS at 1 year (p≤0.033) . In conclusion, this randomized pilot study suggests etanercept may improve early islet engraftment. The long-term effect of etanercept or A1AT on islet engraftment is less clear, though speculatively females may have a sex-specific benefit. Disclosure T.R.Abdel-karim: None. J.S.Hodges: None. T.L.Pruett: None. K.Ramanathan: None. G.Beilman: None. M.Bellin: Advisory Panel; Insulet Corporation, Research Support; Dexcom, Inc., Viacyte. Funding National Institute of Health (R01DK109914)