Off Label Use of Infliximab in Adult Patients With Severe Eosinophilic Esophagitis
Condition: Esophagitis
MeSH terms: Esophagitis; Eosinophilic Esophagitis
Study type: Interventional
Phase: Phase 2

Summary: 
      Eosinophilic Esophagitis (EE) is a chronic inflammatory disorder of the esophagus with a
      constantly increasing prevalence. It has been demonstrated that the expression of the
      cytokine TNF-α is up regulated in EE and that this pro-inflammatory cytokine is highly
      expressed by the keratinocytes of the esophageal epithelium in patients with active EE.
      Furthermore, it has been shown that TNF-α is capable to induce eotaxin-3 production in
      keratinocytes. These results suggest that TNF-α plays a crucial role in the pathogenesis of
      EE. Based on these findings, the investigators plan a prospective T1 translational study with
      the purpose to evaluate the efficacy of an Infliximab monotherapy in adult patients with
      severe, corticosteroid-dependent EE.
    

Detailed description: 
      Study Principle: An open-conducted, un-controlled, off label use of Infliximab will be
      performed in at least 3 individuals with Eosinophilic Esophagitis (EE) to evaluate the
      efficacy of an TNF-α blockade in the treatment of adult patients with severe, isolated EE.

      Rationale for this Trial: Eosinophilic Esophagitis is a chronic, TH2-type dominant
      inflammatory disorder of the esophagus with a constantly increasing prevalence. It has been
      demonstrated that the cytokines TNF-α and IL-5 as well as the chemokine eotaxin-3 play a
      crucial role in the immuno-pathogenesis of this disease. These mediators are potential
      targets for therapeutic interventions. The established diagnostic criteria of EE are
      PPI-resistent esophageal related symptoms in combination with an infiltration of the
      esophageal mucosa with more than 20 eosinophils/hpf, a tissue where eosinophils are not
      normally encountered.

      Treatment strategies in chronic inflammations have basically two goals: 1) Relief of
      symptoms; and 2) Prevention of long-term damage of the affected organ, due to a persistence
      of an uncontrolled inflammation. Standard recommendations for medical therapy of EE include
      systemic or topical corticosteroids and leukotriene antagonists. The treatment with
      corticosteroids is limited by the occurence of steroid-dependence and steroid-resistance, as
      well as the corticosteroid adherent side effects.

      Infliximab, a chimeric monoclonal IgG antibody, is a potent inhibitor of the soluble and the
      membrane-bound form of TNF-α. Its efficacy in inducing and maintaining a remission in several
      TH1- and TH2-type inflammations is well documented. Infliximab is since more than 5 years
      approved for the therapy of these immune-mediated inflammations. Today, it is used as
      standard therapy in a subset of severe forms in these disorders. Meanwhile an overwhelming
      mass of data has confirmed the efficacy and the safety of this compound.

      Purpose of this Study:The purpose of this pilot-trial is to evaluate the efficacy of a TNF-α
      blockade with Infliximab monotherapy as induction-treatment in adult patients with severe EE.
    

Intervention name(s): Infliximab
Intervention type(s): Drug
Intervention description(s): Induction therapy with 2 infusions, each 5 mg/kg body weight within 2 wks
Other intervention name(s): Remicade
Intervention MeSH terms: Infliximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Eosinophilic Esophagitis; TNF-alpha; TNF-alpha Blockade; Infliximab