Methods for Treating Eosinophilic Esophagitis

Abstract

The present invention relates to methods for identifying an EoE endotype of a patient and treating the patient with one or more therapies targeted to the patient's disease endotype; and related methods for stratifying patients for clinical trials.

What is claimed is: 
     
         1 . A method for treating eosinophilic esophagitis (EoE) in a subject determined to have a severe form of EoE, the method comprising
 subjecting a biological sample from the subject to a method for gene expression analysis,   determining the expression of a panel of genes in the biological sample, the panel comprising ANO1, CRYM, DSG1, PNLIPRP3, TNFAIP6, TSLP, UPK1A, and WDR36,   determining the subject's EoE endotype as mild, intermediate, or severe based on the expression of the panel of genes, and   treating the patient with an EoE therapy comprising one or more of esophageal dilation, anti-cytokine therapy, and glucocorticoid therapy where the EoE endotype is determined to be severe, or   treating the patient with one or more of an anti-cytokine therapy, an anti-TSLP therapy, and an anti-ALOX15 therapy where the EoE endotype is determined to be intermediate, or   treating the patient with one or both of proton pump inhibitor (PPI) therapy and dietary therapy where the EoE endotype is determined to be mild;   
     
     
         2 . The method of  claim 1 , wherein the panel of genes further comprises one or more of the genes set forth in Table 2. 
     
     
         3 . The method of  claim 1 , wherein the panel of genes further comprises one or more of ALOX15, APOBEC3A, CDA, CRISP3, ACTG2, CCR3, FFAR3, IL4, RGS9BP, TSLP, CTNNAL1, EML1, FLG, PNLIPRP3 and TSPAN12. 
     
     
         4 . The method of  claim 1 , wherein the biological sample is an esophageal biopsy sample. 
     
     
         5 . The method of  claim 1 , wherein the determining the expression of a panel of genes in the biological sample is performed using a PCR-based method. 
     
     
         6 . The method of  claim 1 , wherein the determining the subject's EoE endotype based on the expression of the panel of genes is performed by a method comprising linear discriminant analysis. 
     
     
         7 . The method of  claim 6 , wherein the linear discriminant analysis comprises determining a probability distance. 
     
     
         8 . The method of  claim 7 , wherein the distance is the Mahalanobis distance. 
     
     
         9 . The method of  claim 1 , wherein the endotype is further characterized by one or more histologic, endoscopic, or clinical features. 
     
     
         10 . The method of  claim 9 , wherein the one or more histologic features is selected from basal zone hyperplasia (BZH) and surface epithelial alteration (SEA). 
     
     
         11 . The method of  claim 9 , wherein the one or more endoscopic features is selected from the occurrence of edema, exudates, and furrows. 
     
     
         12 . The method of  claim 9 , wherein the one or more clinical features is selected from pediatric onset, adult onset, atopic, non-atopic, steroid sensitivity, steroid refractory, and fibrostenotic.