TABLE 2:
BOLOGICS FOR TREATMENT OF EOE.
| Target | Mechanism | Medications | Study Design & Outcome | References |
|---|---|---|---|---|
| IgE | IgE bound to mast cells & basophils cause degranulation on antigen recognition. Role of IgE in EoE is unclear. | Omalizumab | ◦ Open label, 24 pts (age 14–71 yr). 33% with improved histology but no improvement in symptoms ◦ RDBCT, 27 adult & 3 children. No improvement in histology |
[80, 130, 131] |
| IL-5 | Elevated IL-5 has been described in numerous EoE studies | Mepolizumab | ◦ RDBCT, 11 adults. No patients with patients with <5 eos/hpf but some with significant improvement in histology ◦ RDBCT, 59 children (age 2–17 yr). 8.8% of patients with <5 eos/hpf; significant improvement in histology but symptoms not improved |
[110, 111, 132] |
| Reslizumab | RDBCT, 226 children (age 5–18 yr). Significant improvement in pathology with reslizumab (59%–67%) compared with placebo (24%); No significant improvement in Children’s Health Questionnaire or physician assessment of symptoms | [113] | ||
| IL-13 | IL-13 is increased in EoE, induces eotaxin-1, eotaxin-2, and eotaxin-3 expression via STAT6, and causes epithelial barrier dysfunction | QAX576 | RDBCT, 25 adults. After 12 weeks, 40% of QAX576 group had 75% reduction in peak esophageal count on biopsy (13% in placebo group). No difference in Mayo dysphagia symptom questionnaires. | [115] |
| IL-4rα | IL-4 is increased in EoE. IL-4 and IL-13 receptor for heterodimer with IL-4rα subunit: therapy blocking IL-4 signaling through IL4Ralpha will block both IL-4 and IL-13 pathways. | Dupilumab | RDBCT with 47 adult patients. With Dupilumab, histologic score, distensibility, and Straumann dysphagia score were improved at week 12 | [116] |
| TNF-α | TNF-α is increased in epithelium of EoE patients [4–6] | Infliximab | Open label, nonrandomized study. No significant difference in histology, however, two of three adult patients had improved symptoms[133]. | [133] |
| CRTH2 | Chemoattractant receptor-homologous molecule on TH2 cells (CRTH2) is the receptor for prostaglandin D2. ↑ prostaglandin D2 has been seen in plasma from EoE patients | OC000459 | RDBPCT of 26 adults with active EoE randomized to OC000459 or placebo. Esophageal eosinophil load decreased significantly, from 114.83 to 73.26 eos/hpf in OC000459 group with significant improvement in physician assessed disease activity[114][115][115][115][114][114](114). | [114][7] |
RDBPCT= Randomized Double Blind Placebo Controlled Trial; IL= interleukin; Ig+ Immunoglobulin; TNF= Tumor Mecrosis Factor; CRTH2= Chemoattractant receptor-homologous molecule on TH2 cells