Use of Teplizumab to Modulate Stage 2 Type 1 Diabetes in Two Individuals With Autoimmune Polyendocrine Syndrome 1.

OBJECTIVE: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare, monogenic autoimmune disorder that may manifest as type 1 diabetes (T1D). Teplizumab, an anti-CD3 monoclonal antibody, delays progression of stage 2 T1D, but its effects in APS-1-associated diabetes are unknown. RESEARCH DESIGN AND METHODS: We report clinical responses of two adolescents with APS-1 and stage 2 T1D who received 14-day courses of teplizumab. In one patient, pancreatic MRI and spectral immune cell phenotyping were performed before and after treatment. RESULTS: Both patients exhibited improved glycemia. One who briefly required insulin recovered insulin independence 2 weeks after therapy. Pancreatic volume transiently increased, and circulating lymphocytes showed changes in homing receptors and senescence markers in the individual who underwent those studies. Nonpancreatic APS-1 manifestations were unchanged. CONCLUSIONS: Teplizumab may preserve β-cell function in APS-1-associated T1D. Larger studies are needed to define efficacy, durability, and immunologic and tissue mechanisms in this rare context.