Methods for treating or preventing asthma by administering an IL-4R antagonist
The invention provides methods for treating or preventing asthma and associated conditions in a patient. The methods featured in the invention comprise administering to a subject in need thereof a therapeutic composition comprising an interleukin-4 receptor (IL-4R) antagonist, such as an anti-IL-4R antibody.
1 . A method for add-on maintenance treatment of moderate to severe asthma in a subject in need thereof comprising administering to the subject an initial dose of 600 mg of an antibody 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
one or more secondary doses of 300 mg of the antibody.
2 . The method of claim 1 , wherein the antibody 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 3 , wherein the one or more secondary doses are administered every other week (q2w).
5 . The method of claim 4 , wherein the one or more secondary doses are administered for at least 24 weeks.
6 . The method of claim 5 , wherein the dupilumab is administered to the subject subcutaneously.
7 . The method of claim 6 , wherein the subject has a blood eosinophil count of greater than or equal to 300 cells/μL.
8 . The method of claim 6 , wherein one or both of inhaled corticosteroid (ICS) and long-acting beta-agonist (LABA) are administered for the duration of administration of the dupilumab, wherein the ICS is selected from the group consisting of mometasone furoate, budesonide, and fluticasone propionate, and wherein the LABA is selected from the group consisting of formoterol and salmeterol.
9 . A method for increasing forced expiratory volume in 1 second (FEV1) in liters to treat moderate to severe 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) an initial dose of 600 mg of an antibody 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 secondary doses of 300 mg of the antibody,
wherein the ICS and LABA are administered for the duration of administration of the antibody.
10 . A method for improving one or more moderate to severe 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) an initial dose of 600 mg of an antibody that specifically binds to IL-4R comprising three 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 secondary doses of 300 mg of the antibody,
wherein the ICS and LABA are administered for the duration of administration of the antibody.
11 . A method for reducing an asthma patient's dependence on one or both of ICS and LABA for the treatment of one or more moderate to severe asthma exacerbations 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) an initial dose of 600 mg of an antibody 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 secondary doses of 300 mg of the antibody, wherein the ICS and LABA are administered for the duration of administration of the antibody.
12 . The method of claim 8 , wherein the subject is 12 years of age and above.
13 . A method for add-on maintenance treatment of moderate to severe asthma in a subject in need thereof comprising administering to the subject
an initial dose of 400 mg of an antibody or 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
one or more secondary doses of 200 mg of the antibody.
14 . The method of claim 13 , wherein the antibody that specifically binds to IL-4R comprises an HCVR comprising the amino acid sequence of SEQ ID NO: 1 and an LCVR comprising the amino acid sequence of SEQ ID NO: 2.
15 . The method of claim 14 , wherein the antibody is dupilumab.
16 . The method of claim 15 , wherein the one or more secondary doses are administered every other week (q2w).
17 . The method of claim 16 , wherein the secondary doses are administered for at least 24 weeks.
18 . The method of claim 3 , wherein the dupilumab is administered to the subject subcutaneously.
19 . The method of claim 18 , wherein the subject has a blood eosinophil count of greater than or equal to 300 cells/μL.
20 . The method of claim 18 , wherein one or both of ICS and LABA are administered for the duration of administration of the dupilumab, wherein the ICS is selected from the group consisting of mometasone furoate, budesonide, and fluticasone propionate, and wherein the LABA is selected from the group consisting of formoterol and salmeterol.
21 . The method of claim 20 , wherein the subject is 12 years of age and above.
22 . A method for increasing FEV1 in liters to treat moderate to severe 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) an initial dose of 400 mg of an antibody 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 secondary doses of 200 mg of the antibody,
wherein the ICS and LABA are administered for the duration of administration of the antibody.
23 . A method for improving one or more moderate to severe 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) an initial dose of 400 mg of an antibody 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 secondary doses of 200 mg of the antibody,
wherein the ICS and LABA are administered for the duration of administration of the antibody.
24 . A method for reducing an asthma patient's dependence on one or both of ICS and LABA for the treatment of one or more exacerbations of moderate to severe 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) an initial dose of 400 mg of an antibody 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 secondary doses of 200 mg of the antibody,
wherein the ICS and LABA are administered for the duration of administration of the antibody.
25 . A method for add-on maintenance treatment of moderate to severe asthma in a subject in need thereof, comprising administering to the subject by subcutaneous injection an initial dose of 600 mg of dupilumab, and one or more secondary doses of 300 mg of dupilumab administered every other week (q2w), wherein the subject is 12 years of age and above, and wherein the subject has an eosinophilic phenotype.
26 . A method for add-on maintenance treatment of moderate to severe asthma in a subject in need thereof, comprising administering to the subject by subcutaneous injection an initial dose of 400 mg of dupilumab, and one or more secondary doses of 200 mg of dupilumab administered every other week (q2w), wherein the subject is 12 years of age and above, and wherein the subject has an eosinophilic phenotype.
27 . The method of claim 6 , where the dupilumab is administered subcutaneously using an autoinjector, a needle and syringe, or a pen delivery device.
28 . The method of claim 18 , where the dupilumab is administered subcutaneously using an autoinjector, a needle and syringe, or a pen delivery device.
29 . The method of claim 6 , wherein the subject has a blood eosinophil count of 200 to 299 cells/μL.
30 . The method of claim 3 , wherein the subject has a blood eosinophil count of less than 200 cells/μL.
31 . The method of claim 18 , wherein the subject has a blood eosinophil count of 200 to 299 cells/μL.
32 . The method of claim 18 , wherein the subject has a blood eosinophil count of less than 200 cells/μL.
33 . The method of claim 25 , wherein the subject has a blood eosinophil count of greater than or equal to 300 cells/μL.
34 . The method of claim 26 , wherein the subject has a blood eosinophil count of greater than or equal to 300 cells/μL.
35 . The method of claim 33 , wherein the subject has moderate persistent asthma.
36 . The method of claim 33 , wherein the subject has severe persistent asthma.
37 . The method of claim 34 , wherein the subject has moderate persistent asthma.
38 . The method of claim 34 , wherein the subject has severe persistent asthma.