Off Label Use of Infliximab in Adult Patients With Severe Eosinophilic Esophagitis (IEE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00523354
Recruitment Status : Completed
First Posted : August 31, 2007
Last Update Posted : April 7, 2009
Information provided by:
Swiss EE Study Group

Brief 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.

Condition or disease Intervention/treatment Phase
Esophagitis Drug: Infliximab Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Proof-of-Concept Study to Analyze the Efficacy of in TNF-Alpha Blockade in Adult Patients With Severe, Corticosteroid-Dependent Eosinophilic Esophagitis
Study Start Date : August 2007
Actual Primary Completion Date : September 2007
Actual Study Completion Date : October 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Infliximab
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1 (open-label)
prospective, open label, uncontrolled trial
Drug: Infliximab
Induction therapy with 2 infusions, each 5 mg/kg body weight within 2 wks
Other Name: Remicade

Primary Outcome Measures :
  1. Tissue eosinophilia before and after therapy

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult patients with severe, corticosteroid-dependent eosinophilic esophagitis

Exclusion Criteria:

  • Pregnancy
  • Evidence of latent or active tuberculosis
  • Other contra-indications for TNF-alpha blockers
  • Unstable medical conditions
  • Malignancies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00523354

EE-Clinics, Praxis Roemerhof
Olten, SO, Switzerland, 4600
Sponsors and Collaborators
Swiss EE Study Group
Study Chair: Hans-Uwe Simon, MD and PhD Deaprtment of Pharmacology, University Bern, Bern, Switzerland Identifier: NCT00523354     History of Changes
Other Study ID Numbers: Swiss EE-Study Group
First Posted: August 31, 2007    Key Record Dates
Last Update Posted: April 7, 2009
Last Verified: April 2009

Keywords provided by Swiss EE Study Group:
Eosinophilic Esophagitis
TNF-alpha Blockade

Additional relevant MeSH terms:
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Immune System Diseases
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents