Methods for treating active eosinophilic esophagitis

Abstract

The present invention provides methods for treating, preventing or reducing the severity of active eosinophilic esophagitis. In certain embodiments, the present invention provides methods of increasing esophageal distensibility. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4/interleukin-13 (IL-4/IL-13) pathway inhibitor such as an anti-IL-4R antibody.

What is claimed is: 
     
         1 . A method of reducing dysphagia comprising:
 administering a therapeutically effective amount of a pharmaceutical composition comprising an interleukin-4/interleukin-13 (IL-4/IL-13) pathway inhibitor to a patient in need thereof,   wherein the patient has eosinophilic esophagitis (EoE), and wherein the patient exhibits at least two episodes of dysphagia per week for at least four weeks and/or has a Straumann Dysphagia Instrument (SDI) score ≥5;   wherein the IL-4/IL-13 pathway inhibitor is an antibody or antigen-binding fragment thereof that binds IL-4 receptor alpha (IL-4Rα), wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3), wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 7, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 8, thereby reducing dysphagia.   
     
     
         2 . The method of  claim 1 , wherein the patient has had EoE for at least three years. 
     
     
         3 . The method of  claim 1 , wherein the patient is ≥18 years of age. 
     
     
         4 . The method of  claim 1 , wherein the patient has been treated previously with proton pump inhibitors (PPIs). 
     
     
         5 . The method of  claim 1 , wherein the patient has had at least one prior esophageal dilation. 
     
     
         6 . The method of  claim 1 , wherein the patient to be treated:
 (1) has a history of at least one other disease or condition selected from the group consisting of food allergy, allergic rhinitis, non-food allergy, asthma, chronic sinusitis, hives, atopic dermatitis, and allergic conjunctivitis;   (2) has a baseline SDI score >7; and/or   (3) has a baseline Eosinophilic Esophagitis Severity and Activity Index (EEsAI) score ≥50.   
     
     
         7 . The method of  claim 1 , wherein administration of the IL-4/IL-13 pathway inhibitor results in improvement of at least one parameter selected from the group consisting of:
 (a) reduction of at least 40% from baseline in the SDI score;   (b) reduction of ≥3 points from baseline in the SDI score; and   (c) reduction of more than 30% from baseline in Eosinophilic Esophagitis Severity and Activity Index (EEsAI) score.   
     
     
         8 . The method of  claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered at a dose of about 50 to about 600 mg. 
     
     
         9 . The method of  claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered at a dose of about 300 mg. 
     
     
         10 . The method of  claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered at an initial dose followed by one or more secondary doses, wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose. 
     
     
         11 . The method of  claim 10 , wherein the initial dose comprises 50 mg-600 mg of the IL-4/IL-13 pathway inhibitor. 
     
     
         12 . The method of  claim 10 , wherein each secondary dose comprises 25 mg-400 mg of the IL-4/IL-13 pathway inhibitor. 
     
     
         13 . The method of  claim 10 , wherein the initial dose comprises 600 mg of the IL-4/IL-13 pathway inhibitor, and each secondary dose comprises 300 mg of the IL-4/IL-13 pathway inhibitor. 
     
     
         14 . The method of  claim 13 , wherein each secondary dose is administered one week or two weeks after the immediately preceding dose. 
     
     
         15 . The method of  claim 9 , wherein the IL-4/IL-13 pathway inhibitor is administered once every week or once every two weeks. 
     
     
         16 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered in combination with a second therapeutic agent or therapy, wherein the second therapeutic agent or therapy is selected from the group consisting of an IL-1beta inhibitor, an IL-5 inhibitor, an IL-9 inhibitor, an IL-13 inhibitor, an IL-17 inhibitor, an IL-25 inhibitor, a TNFalpha inhibitor, an eotaxin-3 inhibitor, an IgE inhibitor, a prostaglandin D2 inhibitor, an immunosuppressant, a topical corticosteroid, an oral corticosteroid, a systemic corticosteroid, an inhaled corticosteroid, a glucocorticoid, a proton pump inhibitor, a NSAID, esophagus dilation, allergen removal, and/or diet management. 
     
     
         22 . The method of  claim 1 , wherein the IL-4/IL-13 pathway inhibitor is administered subcutaneously. 
     
     
         23 - 30 . (canceled) 
     
     
         31 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) that comprises the amino acid sequence of SEQ ID NO: 1, and a light chain variable region (LCVR) that comprises the amino acid sequence of SEQ ID NO: 2. 
     
     
         32 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10. 
     
     
         33 . The method of  claim 1 , wherein the IL-4/IL-13 pathway inhibitor is dupilumab or a bioequivalent thereof. 
     
     
         34 . (canceled)