Biologics in eosinophilic gastrointestinal diseases

Abstract

Eosinophilic gastrointestinal diseases are a constellation of conditions categorized by the location of eosinophilic infiltration in the gastrointestinal tract. Symptoms vary based on location of eosinophils and age of the patient. There are no approved medications at the current time with individuals using off-label steroids or dietary therapy. Translational research has identified potential pathways to target in the treatment of eosinophilic esophagitis (EoE), gastritis (EoG), and enteritis (EoN), including type 2 pathways, mast cells, and eosinophils. Preliminary studies found cendakimab (anti-interleukin [IL]-13) and dupilumab (anti-IL-4 receptor alpha) to have an effect on eosinophil count and symptoms with dupilumab recently approved. In addition, mepolizumab (anti-IL-5), reslizumab (anti-IL-5), and lirentelimab (anti-Siglec 8) were found to have reduction in eosinophils without reduction of symptoms. For EoG and EoN, both benralizumab (anti-IL-5 receptor) and lirentelimab were found to have histologic and symptom improvement. There are no agents studied for eosinophilic colitis. Results of ongoing phase 3 trials in EoE and EoG/EoN are also anticipated.

Figure 1.

Identification of therapeutic targets from the current model for EoE pathogenesis and the T2 inflammatory cascade. Biologics can target circulating cytokines (cendakimab, mepolizumab, reslizumab, tezepelumab, CALY-002), receptors (dupilumab, lirentelimab, benralizumab), or integrins (vedolizumab). EoE, eosinophilic esophagitis.

Figure 2.

Potential points where a biologic agent could be positioned in the EoE treatment algorithm. Use for treatment-refractory patients is a clear place for these agents (red box). As more is known about the safety, efficacy, and costs, these medications could be used earlier in the algorithm as first-line agents (red arrow), or in a targeted or personalized approach, for example, for patients who have fibrostenotic disease (red double arrow). With less frequent administration, a role for maintenance is also possible (red dashed arrow). EoE, eosinophilic esophagitis.