Methods for treating skin infection by administering an il-4r antagonist

Abstract

The present invention provides methods for treating, preventing or ameliorating skin infections, including bacterial and viral infections. In certain embodiments, the invention provides methods to reduce skin infection in a patient with atopic dermatitis (AD). Also provided are methods for improving skin barrier function, and methods for reducing the risk of inflammation due to microbial infection in a patient in need thereof. The methods of the present invention comprise administering to a patient in need thereof a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody.

What is claimed is: 
     
         1 - 54 . (canceled) 
     
     
         55 . A method of improving skin barrier function in a subject with atopic dermatitis, the method comprising administering to the subject a pharmaceutical composition comprising an IL-4R antagonist, wherein the subject exhibits reduced stratum corneum hydration (SCH), elevated level of transepidermal water loss (TEWL), elevated skin surface pH, or an elevated skin roughness profilometry;
 wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) of a heavy chain variable region (HCVR) comprising SEQ ID NO: 1, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) of a light chain variable region (LCVR) comprising SEQ ID NO: 2;   wherein the IL-4R antagonist is administered at an initial dose followed by one or more secondary doses, wherein the initial dose and each secondary dose comprises about 50 mg to about 600 mg of the IL-4R antagonist, wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose.   
     
     
         56 . The method of  claim 55 , wherein the skin is lesional. 
     
     
         57 . The method of  claim 56 , wherein the lesional skin is positive for  S. aureus.    
     
     
         58 . The method of  claim 55 , wherein the skin is non-lesional. 
     
     
         59 . The method of  claim 58 , wherein the non-lesional skin is positive for  S. aureus.    
     
     
         60 . The method of  claim 55 , wherein the subject has moderate-to-severe atopic dermatitis. 
     
     
         61 . The method of  claim 55 , wherein the pharmaceutical composition is administered subcutaneously. 
     
     
         62 . The method of  claim 55 , wherein HCDR1 comprises SEQ ID NO: 3, HCDR2 comprises SEQ ID NO: 4, HCDR3 comprises SEQ ID NO: 5, LCDR1 comprises SEQ ID NO: 6, LCDR2 comprises SEQ ID NO: 7, and LCDR3 comprises SEQ ID NO: 8. 
     
     
         63 . The method of  claim 55 , wherein the antibody or antigen-binding fragment thereof comprises a HCVR comprising the amino acid sequence of SEQ ID NO:1 and a LCVR comprising the amino acid sequence of SEQ ID NO:2. 
     
     
         64 . The method of  claim 55 , wherein the IL-4R antagonist is dupilumab or a bioequivalent thereof. 
     
     
         65 . The method of  claim 55 , wherein the initial dose of the IL-4R antagonist is 600 mg and each secondary dose of the IL-4R antagonist is 300 mg. 
     
     
         66 . The method of  claim 65 , wherein each secondary dose is administered one week or two weeks after the immediately preceding dose. 
     
     
         67 . A method of decreasing transepidermal water loss (TEWL) in a subject, the method comprising administering to a subject with atopic dermatitis a pharmaceutical composition comprising an IL-4R antagonist at an initial dose followed by one or more secondary doses;
 wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) of a HCVR comprising SEQ ID NO: 1, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) of a LCVR comprising SEQ ID NO: 2;   wherein the initial dose and the one or more secondary doses of IL-4R antagonist are about 50 mg to about 600 mg, and wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose.   
     
     
         68 . The method of  claim 67 , wherein the subject has an elevated level of skin TEWL relative to a person without atopic dermatitis. 
     
     
         69 . The method of  claim 67 , wherein administration of the IL-4R antagonist results in a decrease in a TEWL score of at least 20% from baseline. 
     
     
         70 . The method of  claim 67 , wherein the pharmaceutical composition is administered subcutaneously. 
     
     
         71 . The method of  claim 67 , wherein HCDR1 comprises SEQ ID NO: 3, HCDR2 comprises SEQ ID NO: 4, HCDR3 comprises SEQ ID NO: 5, LCDR1 comprises SEQ ID NO: 6, LCDR2 comprises SEQ ID NO: 7, and LCDR3 comprises SEQ ID NO: 8. 
     
     
         72 . The method of  claim 67 , wherein the antibody or antigen-binding fragment thereof comprises a HCVR comprising the amino acid sequence of SEQ ID NO:1 and a LCVR comprising the amino acid sequence of SEQ ID NO:2. 
     
     
         73 . The method of  claim 67 , wherein the IL-4R antagonist is dupilumab or a bioequivalent thereof. 
     
     
         74 . The method of  claim 67 , wherein the initial dose of the IL-4R antagonist is 600 mg and each secondary dose of the IL-4R antagonist is 300 mg. 
     
     
         75 . The method of  claim 74 , wherein each secondary dose is administered one week or two weeks after the immediately preceding dose. 
     
     
         76 . A method of increasing stratum corneum hydration (SCH) in a subject, the method comprising administering to a subject with atopic dermatitis a pharmaceutical composition comprising an IL-4R antagonist at an initial dose followed by one or more secondary doses;
 wherein the IL-4R antagonist is an antibody or antigen-binding fragment thereof that specifically binds IL-4Rα, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDRs (HCDR1, HCDR2 and HCDR3) of a HCVR comprising SEQ ID NO: 1, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) of a LCVR comprising SEQ ID NO: 2;   wherein the initial dose and the one or more secondary doses of IL-4R antagonist are about 50 mg to about 600 mg, and wherein each secondary dose is administered 1 to 4 weeks after the immediately preceding dose.   
     
     
         77 . The method of  claim 76 , wherein the subject has a decreased level of skin SCH relative to a person without atopic dermatitis. 
     
     
         78 . The method of  claim 76 , wherein administration of the IL-4R antagonist results in an increase in a SCH score of at least 10% from baseline. 
     
     
         79 . The method of  claim 76 , wherein the pharmaceutical composition is administered subcutaneously. 
     
     
         80 . The method of  claim 76 , wherein HCDR1 comprises SEQ ID NO: 3, HCDR2 comprises SEQ ID NO: 4, HCDR3 comprises SEQ ID NO: 5, LCDR1 comprises SEQ ID NO: 6, LCDR2 comprises SEQ ID NO: 7, and LCDR3 comprises SEQ ID NO: 8. 
     
     
         81 . The method of  claim 76 , wherein the antibody or antigen-binding fragment thereof comprises a HCVR comprising the amino acid sequence of SEQ ID NO:1 and a LCVR comprising the amino acid sequence of SEQ ID NO:2. 
     
     
         82 . The method of  claim 76 , wherein the IL-4R antagonist is dupilumab or a bioequivalent thereof. 
     
     
         83 . The method of  claim 76 , wherein the initial dose of the IL-4R antagonist is 600 mg and each secondary dose of the IL-4R antagonist is 300 mg. 
     
     
         84 . The method of  claim 83 , wherein each secondary dose is administered one week or two weeks after the immediately preceding dose.