ABSTRACT
Dupilumab has been approved to treat a variety of atopic disorders and was the first US FDA-approved medication for the treatment of eosinophilic esophagitis (EoE), initially approved in May 2022, with expansion in use to patients as young as 1 year of age weighing at least 15 kg in January 2024. It is a fully human monoclonal antibody that inhibits both IL-4 and IL-13 signaling, suppressing TH2-mediated proinflammatory cytokines, chemokines and IgE implicated in EoE pathogenesis. Phase II and III trials in EoE have demonstrated histologic, endoscopic and symptomatic improvement in disease activity with an overall favorable safety profile. This article will review the available clinical trial data and real-world efficacy of dupilumab in EoE.
Dupilumab is a biologic medication used for the treatment of eosinophilic esophagitis. Clinical trials have shown that this medication is effective in treating both inflammation in the esophagus and symptoms associated with eosinophilic esophagitis in a high proportion of patients. Dupilumab was well tolerated by the majority of clinical trial patients, though side effects such as injection site redness and swelling have been reported. More serious side effects are overall rare.
Subject(s)
Antibodies, Monoclonal, Humanized , Eosinophilic Esophagitis , Interleukin-13 , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/immunology , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Interleukin-13/antagonists & inhibitors , Interleukin-13/metabolism , Interleukin-13/immunology , Interleukin-4/metabolism , Interleukin-4/antagonists & inhibitors , Clinical Trials as Topic , Treatment Outcome , Th2 Cells/immunologyABSTRACT
Enteroendocrine (EE) cells are the most abundant hormone-producing cells in humans and are critical regulators of energy homeostasis and gastrointestinal function. Challenges in converting human intestinal stem cells (ISCs) into functional EE cells, ex vivo, have limited progress in elucidating their role in disease pathogenesis and in harnessing their therapeutic potential. To address this, we employed small molecule targeting of the endocannabinoid receptor signaling pathway, JNK, and FOXO1, known to mediate endodermal development and/or hormone production, together with directed differentiation of human ISCs from the duodenum and rectum. We observed marked induction of EE cell differentiation and gut-derived expression and secretion of SST, 5HT, GIP, CCK, GLP-1 and PYY upon treatment with various combinations of three small molecules: rimonabant, SP600125 and AS1842856. Robust differentiation strategies capable of driving human EE cell differentiation is a critical step towards understanding these essential cells and the development of cell-based therapeutics.