ICPis -induced autoimmune polyendocrine syndrome type 2: a review of the literature and a protocol for optimal management.

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Immune checkpoint inhibitors (ICPis) targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) and its ligand (PD-L1) are now approved to treat a variety of cancers. However, ICPis therapy is associated with a risk of immune-related adverse events (irAEs). Autoimmune polyendocrine syndrome type 2 (APS-2) is a rare endocrine irAE.Several databases (PubMed, Web of Science, Cochrane Central Registry of Controlled Trails, ClinicalTrails.gov, and Scopus) were searched up to February 18 th 2020 for case reports on endocrine irAEs and ICPis. The reported side effects and adverse events of the ICPis therapy in the FDA and EMA adverse events pharmacovigilance registries are also included.Here, we provide an overview of all published and reported cases (n=30) of ICPis-induced APS-2. We summarize the clinical characteristics, autoantibodies, HLA genotypes, and therapies and propose an APS-2 screening strategy.Given the life-threatening risks of endocrine dysfunction if it is not promptly recognized (such as diabetic ketoacidosis and acute adrenal crisis), physicians (especially endocrinologists and oncologists) should be familiar with APS-2. After diagnosis of an autoimmune disease induced by ICPis (especially PD-1 inhibitors), patients with a high-risk human leukocyte antigen allele (HLA-DR4) require close monitoring for the development of APS-2.


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