Endocrine Abstracts

JOINT250

Background and Aims: Type 1 diabetes mellitus (TIDM) in children is an autoimmune disease characterized by progressive destruction of the β cells of the pancreas and lifelong dependency on exogenous insulin. This presentation sheds light on the unique immune mechanisms of newly approved immunotherapy teplizumab and unveiling its breakthrough benefit for children with established T1DM and its impressing role in delaying the onset of the disease among high-risk relatives.

Methods: Retrieved recently published data and documented studies and trials from PubMed, Google Scholar, and the Web of Science using "TIDM and Teplizumab."

Results: Teplizumab is a newly approved humanized IgG1 kappa CD3-directed monoclonal antibody. Its exceptional design as an Fc-non-binding antibody helps to ameliorate and reduce the cytokine release syndrome associated with the adverse autoimmune destruction of pancreatic β cells in children with TIDM. It effectively stops the autoimmune destruction of insulin-producing pancreatic cells by turning off pancreatic-cell autoreactive effector CD8+ T-lymphocytes and making the cells inactive. Therefore, its mechanism seems to enhance regulatory T-cell activity and promote immune tolerance. Compared with controls, the teplizumab clinical trial was found to be an effective strategy to maintain β-cell function, reduce C-peptide decline, preserve insulin production, and reduce exogenous insulin need in children age 8 and older with new-onset T1DM for up to 2 years. More recent clinical trials concluded that the 14-day full dose of teplizumab delays the progression to clinical T1DM in high-risk individuals, resulting in reduced insulin usage and hospital visits.

Discussion: Teplizumab’s unique design and its peculiar immune mechanism to enhance regulatory T-cell activity and promote immune tolerance with its recent trials for children with TIDM are intriguing and herald the start of a new and exciting era of hope in diabetes research and clinical management. Interestingly, trials in different phases revealed that teplizumab stopped β cell destruction in established TIDM and reduced exogenous insulin, delayed the disease onset among high-risk relatives, and significantly slowed progression to clinical TIDM.

Conclusion: Teplizumab is the first FDA-approved breakthrough disease-modifying immunotherapy therapy for children with TID with impressing role in delaying the onset of the disease among high-risk relatives. Despite the approval of teplizumab, the main challenges remain the need for widespread screening programs for early-stage T1DM diagnosis in children and the identification of individuals at high risk within the general population.

Keywords: TIDM, children, Teplizumab immunotherapy