Emerging therapies for eosinophilic esophagitis

Abstract

Despite advances in the pathologic understanding of eosinophilic esophagitis (EoE), as of yet, no single agent has been approved by the US Food and Drug Administration to treat EoE. Off-label, EoE is currently treated by using the 3 Ds: drugs (particularly swallowed topical corticosteroids), dietary restriction, and endoscopic dilation. In the recent past, considerable progress in terms of EoE treatment has been made: (1) new EoE-specific steroid formulations optimizing mucosal deposition have been developed, which has culminated in recent approval of a budesonide effervescent tablet in Europe; (2) biologics used for other T H 2-mediated diseases, such as allergic asthma and atopic eczema, as well as purposedeveloped biologics, have been studied in phase II trials in patients with EoE; and (3) novel dietary restriction strategies have evolved. Finally, further insights into the pathogenesis of EoE have revealed several novel disease mediators that might be targeted in the future. In the following article we will discuss recent advances in EoE treatment with regard to swallowed topical steroids, biological agents, dietary approaches, and novel molecular targets.

In Esophageal Squamous Cells From Eosinophilic Esophagitis Patients, Th2 Cytokines Increase Eotaxin-3 Secretion Through Effects on Intracellular Calcium and a Non-Gastric Proton Pump

“…Clinical trials of biologic agents that target IL-5 and IL-13 have demonstrated significant histologic improvement but only limited symptomatic benefit for patients with EoE, [11][12][13] and agents targeting tumor necrosis factor-a and IgE do not appear to be effective EoE treatments. 13 Among the most promising biologic agents for EoE is dupilumab, a fully humanized monoclonal antibody directed against the IL-4 receptor-a (IL4Ra) through which both IL-4 and IL-13 signal to increase eotaxin-3 production by esophageal squamous cells. 14,15 In a multicenter, randomized, placebo-controlled phase 2 study, dupilumab demonstrated significant efficacy in improving both clinical and histopathologic features of EoE.…”

Tight junctions in the development of asthma, chronic rhinosinusitis, atopic dermatitis, eosinophilic esophagitis, and inflammatory bowel diseases

“…The major outcome is the presence of Th2 lymphocytes with barrier dysregulation 132 . Major cytokines involved in the pathogenesis of eosinophilic esophagitis such as IL‐4, IL‐5, IL‐13, and TNF have been tested for the treatment of eosinophilic esophagitits 133 . Along with Th2 cytokines, TGF‐β is the major cytokine that mediates lamina propria remodeling in eosinophilic esophagitis 134 .…”

Dilation-predominant approach versus routine care in patients with difficult-to-treat eosinophilic esophagitis: a retrospective comparison

“…The dilate and wait strategy was also safe and provided a bridge to clinical trials with novel treatments in almost half of patients. Given the rapidity with which new treatments for EoE are being developed [30], as well as the sizable proportion of EoE patients who are nonresponsive to first-line treatment options [31], this approach is reasonable in these patients who might ultimately benefit from new therapies [25].…”