**5.4 EoE**

Overall, EoE is treated with three main categories: drugs, diet, and dilation [163–165]. The diet therapy has been discussed in a previous section. Pharmacological treatment includes topical corticosteroids, such as fluticasone or budesonide, swallowed rather than inhaled, for an initial duration of 8 weeks. It has been shown that the patients' symptoms have improved as decreased esophageal eosinophilia was apparent, and were generally well-tolerated by patients [166–172]. Proton pump inhibitors (PPI) are usually given to the patients of EoE since the patients usually suffer from regurgitation and acid reflux. The response to PPI is hugely variable between 30 to 70% [173]. PPI-responsive and PPI-resistant EoE have yet to be identified. In patients with PPI-responsive EoE, expression of the potassium channel gene, KCNJ2, is lower. CYP2C19 rapid metabolizers and allergy patients are more likely to lose EoE control despite continued PPI treatment [174]. Since the long-term use of corticosteroids can result in harmful effects, immunomodulators, such as 6-mercaptopurine and azathioprine, are often used for the treatment of the patients. They might have a role in inducing and maintaining long-term clinical and histologic remission in EoE in limited cases but their side effects can be discouraging [175, 176]. Monoclonal antibodies have been investigated in the last few years against EoE including some famous drugs including mepolizumab (anti-IL-5), reslizumab (anti-IL-5), QAX576

### *Autoimmune Diseases of the GI Tract Part II: Emergence of Diagnostic Tools and Treatments DOI: http://dx.doi.org/10.5772/intechopen.106185*

(anti-IL-13), omalizumab (anti-immunoglobulin-E), and infliximab (anti-TNF-α) [177]. IL-5 produced by Th2 lymphocytes has a critical role in eosinophil activation. Animal studies have shown that overexpression of IL-5 can induce EoE [178, 179]. IL-5 receptors, which are mainly expressed on the surface of eosinophils, are blocked by mepolizumab, a monoclonal antibody against IL-5 [180]. The use of mepolizumab seems promising in decreasing the number of eosinophils and reducing the dependency on corticosteroids but more clinical studies need to be conducted [181–183]. Another humanized anti-IL-5 mAb called reslizumab prevents IL-5 from binding to its receptor. The available trials show an improvement in eosinophil count but not in the symptoms and the drug was generally safe [184–186]. In the pathogenesis of EoE, IL3 plays a multifunctional role. An anti-IL3 therapy could be efficient in EoE one of the most famous anti-IL13 drugs is QAX576. Patients tolerated QAX576 well. Patients decreased by 60.0% and sustained for 6 months on the QAX576, which is an anti-IL3 drug. Unfortunately, the primary endpoint was not reached. A trend for improved symptoms was observed particularly dysphagia. Six months after treatment, QAX576 helped to improve expression of esophageal transcripts related to EoE, such as eotaxin-3, periostin, and markers of mast cells and barrier function [187]. Since mast cells are involved in the pathogenesis of EoE, targeting them directly could be an efficient treatment for EoE. Malizumab is a monoclonal anti-IgE antibody that prevents mast cell activation by binding to IgE [188]. However, in most of the trials, the response was poor in patients or reoccurrence of symptoms presented after a short time [189–191]. TNF-α and IFN-γ are found in esophageal mucosal biopsy of the EoE patients. A potent inhibitor of TNF-α is infliximab that is a chimeric IgG1mAb. Infliximab was not shown to be of no benefit for EoE patients [192].

Dilation is also sometimes used in the treatment of EoE. The most common use of esophageal dilation is in adults with EoE and strictures. Conservatively applied, this approach is safe and has a low complication rate. Dilation treats structural alterations in EoE. Although esophageal dilation is well tolerated by patients and can provide long-term symptomatic relief, it does not improve histologic changes [193–195].

## **5.5 IBD**

IBD can have a wide range of treatments. In Crohn's disease, treatments include immunomodulators, corticosteroids, and monoclonal antibodies. 5-aminosalicylates is the most commonly prescribed for symptoms management in mild and moderate disease [196]. Corticosteroids are efficient, prednisone can be efficient in the course of treatment [197]. Budesonide (Entocort EC) may be preferred for diseases affecting the ileum and/or proximal colon since it is delivered specifically to those areas [196]. Immunomodulators, such as thiopurines and methotrexate are the most effective immunomodulators used in Crohn's disease [198]. Anti-TNF agents, anti-integrin agents, and anti-interleukin-12/23p40 antibody therapy are considered the most efficient in treating Crohn's disease. The continuation of any of them in the treatment plan depends on the remission success [199]. In moderate- to high-risk patients, anti-TNF agents, such as certolizumab pegol (Cimzia) and adalimumab (Humira) induce and maintain remission, or patients with inadequate responses to corticosteroids or immunomodulators [200]. In anti-integrin agents, vedolizumab is the most favorable drug because of its specificity to leukocyte trafficking in the gut and has demonstrated effectiveness in achieving clinical response, remission, and corticosteroid-free remission [201]. In, anti-interleukin-12/23p40, ustekinumab is promising for Crohn's disease as it was recently approved by FDA [202]. In Crohn's disease, 57% of the


### **Table 2.**

*Common treatments for GI autoimmune.*

patients might need surgical intervention to treat fistulas, abscesses, perforation, obstruction, strictures, uncontrolled bleeding, dysplasia, malignancy, and perianal disease [196, 203].

In UC, the treatment options do not differ much from Crohn's Disease. The mainstay of therapy for mild-to-moderate UC is sulfasalazine and other 5-ASA agents [204]. Corticosteroids are also efficient in UC patients and it's usually given to the cases of severe symptoms. Prednisone is the most used corticosteroid. Immunomodulators are also used such as their usage in Crohn's Disease. Azathioprine and 6-mercaptopurine (6-MP) are purine analogs that are the commonly most used in the treatment [205]. Also, monoclonal antibodies used in UC such as infliximab has proven their efficiency [206]. In addition, vedolizumab has proven to be efficient as well in UC [207]. Surgical treatment is an option as well in UC. This is generally considered a last resort when all other options have failed. The most common type of surgery is a subtotal or total colectomy with a temporary stoma [208]. Also, laparoscopic surgeries are a safe option in UC (**Table 2**) [209].
