Methods for treating or preventing asthma by administering an IL-4R antagonist

1. A method for treating persistent asthma in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an inhaled corticosteroid (ICS),

ii) one or more maintenance doses of a long-acting beta 2 -adrenergic agonist (LABA),

iii) a loading dose of about 600 mg of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R) comprising three Heavy chain Complementarity Determining Region (HCDR) sequences comprising SEQ ID NOs: 3, 4, and 5, and three Light chain Complementarity Determining Region (LCDR) sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more maintenance doses of about 300 mg of the antibody or the antigen-binding fragment thereof,

wherein the ICS and LABA are administered for the duration of administration of the antibody or the antigen-binding fragment thereof.

2. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof that specifically binds to IL-4R comprises a Heavy Chain Variable Region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a Light Chain Variable Region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

3. The method of claim 2 , wherein the antibody is dupilumab.

4. The method of claim 1 , wherein the one or more maintenance doses are administered every other week (q2w).

5. The method of claim 4 , wherein the maintenance doses of the antibody or antigen-binding fragment thereof are administered for at least 24 weeks.

6. The method of claim 1 , wherein the one or more maintenance doses are administered every fourth week (q4w).

7. The method of claim 6 , wherein the maintenance doses of the antibody or antigen-binding fragment thereof are administered for at least 24 weeks.

8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is administered to the subject systemically, subcutaneously, intravenously, or intranasally.

9. The method of claim 1 , wherein the subject has a blood eosinophil count selected from the group consisting of: greater than or equal to 300 cells/μL, 200 to 299 cells/μL; and less than 200 cells/μL.

10. The method of claim 1 , wherein the ICS is selected from the group consisting of: mometasone furoate, budesonide, and fluticasone propionate.

11. The method of claim 1 , wherein the LABA is selected from the group consisting of: formoterol and salmeterol.

12. The method of claim 1 , wherein the subject is 12 years of age and above.

13. A method for increasing Forced Expiratory Volume in 1 second (FEV1) in liters to treat persistent asthma in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) a loading dose of about 600 mg of an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more maintenance doses of about 300 mg of the antibody or the antigen-binding fragment thereof,

wherein the ICS and LABA are administered for the duration of administration of the antibody or the antigen-binding fragment thereof.

14. A method for improving one or more persistent asthma-associated parameter(s) in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) a loading dose of about 600 mg of an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more maintenance doses of about 300 mg of the antibody or the antigen-binding fragment thereof,

wherein the ICS and LABA are administered for the duration of administration of the antibody or the antigen-binding fragment thereof.

15. A method for reducing an asthma patient's dependence on ICS and/or LABA for the treatment of one or more exacerbations of persistent asthma comprising:

(a) selecting a patient who has moderate-to-severe asthma that is uncontrolled with a background asthma therapy comprising an ICS, a LABA, or a combination thereof; and

(b) administering to the patient a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) a loading dose of about 600 mg of an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more maintenance doses of about 300 mg of the antibody or the antigen-binding fragment thereof,

wherein the ICS and LABA are administered for the duration of administration of the antibody or the antigen-binding fragment thereof.

16. A method for treating persistent asthma in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an inhaled corticosteroid (ICS),

ii) one or more maintenance doses of a long-acting beta 2 -adrenergic agonist (LABA),

iii) a loading dose of about 400 mg of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R) comprising three Heavy chain Complementarity Determining Region (HCDR) sequences comprising SEQ ID NOs: 3, 4, and 5, and three Light chain Complementarity Determining Region (LCDR) sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more maintenance doses of about 200 mg of the antibody or the antigen-binding fragment thereof,

wherein the ICS and LABA are administered for the duration of administration of the antibody or the antigen-binding fragment thereof.

17. The method of claim 16 , wherein the antibody or antigen-binding fragment thereof that specifically binds to IL-4R comprises a Heavy Chain Variable Region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a Light Chain Variable Region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2.

18. The method of claim 17 , wherein the antibody is dupilumab.

19. The method of claim 16 , wherein the one or more maintenance doses are administered every other week (q2w).

20. The method of claim 19 , wherein the maintenance doses of the antibody or antigen-binding fragment thereof are administered for at least 24 weeks.

21. The method of claim 16 , wherein the one or more maintenance doses are administered every fourth week (q4w).

22. The method of claim 21 , wherein the maintenance doses of the antibody or antigen-binding fragment thereof are administered for at least 24 weeks.

23. The method of claim 16 , wherein the antibody or antigen-binding fragment thereof is administered to the subject systemically, subcutaneously, intravenously, or intranasally.

24. The method of claim 16 , wherein the subject has a blood eosinophil count selected from the group consisting of: greater than or equal to 300 cells/μL, 200 to 299 cells/μL; and less than 200 cells/μL.

25. The method of claim 16 , wherein the ICS is selected from the group consisting of: mometasone furoate, budesonide, and fluticasone propionate.

26. The method of claim 16 , wherein the LABA is selected from the group consisting of: formoterol and salmeterol.

27. The method of claim 16 , wherein the subject is 12 years of age and above.

28. A method for increasing Forced Expiratory Volume in 1 second (FEV1) in liters to treat persistent asthma in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) a loading dose of about 400 mg of an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more maintenance doses of about 200 mg of the antibody or the antigen-binding fragment thereof,

wherein the ICS and LABA are administered for the duration of administration of the antibody or the antigen-binding fragment thereof.

29. A method for improving one or more persistent asthma-associated parameter(s) in a subject in need thereof comprising administering to the subject a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) a loading dose of about 400 mg of an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more maintenance doses of about 200 mg of the antibody or the antigen-binding fragment thereof,

wherein the ICS and LABA are administered for the duration of administration of the antibody or the antigen-binding fragment thereof.

30. A method for reducing an asthma patient's dependence on ICS and/or LABA for the treatment of one or more exacerbations of persistent asthma comprising:

(a) selecting a patient who has moderate-to-severe asthma that is uncontrolled with a background asthma therapy comprising an ICS, a LABA, or a combination thereof; and

(b) administering to the patient a combination therapy comprising:

i) one or more maintenance doses of an ICS,

ii) one or more maintenance doses of a LABA,

iii) a loading dose of about 400 mg of an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R comprising three HCDR sequences comprising SEQ ID NOs: 3, 4, and 5, and three LCDR sequences comprising SEQ ID NOs: 6, 7, and 8, and

iv) one or more maintenance doses of about 200 mg of the antibody or the antigen-binding fragment thereof,

wherein the ICS and LABA are administered for the duration of administration of the antibody or the antigen-binding fragment thereof.