METHODS FOR TREATING SEVERE ATOPIC DERMATITIS BY ADMINISTERING AN IL-4R INHIBITOR
The present invention provides methods for treating moderate-to-severe or severe atopic dermatitis (AD). The methods of the present invention comprise administering to a subject in need thereof one or more doses of an interleukin-4 receptor (IL-4R) inhibitor such as an anti-IL-4R antibody. In certain embodiments, the methods of the present invention are used to treat severe AD in a patient whose disease is not controlled with systemic therapy (e.g., cyclosporine A) or when such therapy is inadvisable.
1 . A method of reducing or preventing flares in a patient with atopic dentist (AD), the method comprising
administering a therapeutically effective amount of a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) inhibitor to the patient in need thereof, wherein the patient has moderate to severe AD that is refectory to treatment with a medium-potency topical corticosteroid (TCS), a high-potency TCS, or a systemic immunosuppressant, wherein the IL-4R inhibitor is an antibody or antigen-binding fragment thereof that specifically binds IL-4R, 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.
2 . The method of claim 1 , wherein the patient has severe AD.
3 . The method of claim 1 , wherein the systemic immunosuppressant is selected from the group consisting of cyclosporine A (CSA), methotrexate, mycophenolate mofetil, azathioprine, systemic corticosteroids, and interferon-gamma.
4 . The method of claim 3 , wherein the systemic immunosuppressant is CSA.
5 . The method of claim 1 , wherein the patient to be treated has experienced a prior AD flare.
6 . (canceled)
7 . (canceled)
8 . The method of claim 1 , wherein the IL-4R inhibitor is administered at a dose of about 50-about 600 mg.
9 . The method of claim 8 , wherein the IL-4R inhibitor is administered at a dose of about 300 mg.
10 . The method of claim 1 , wherein the IL-4R 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 about 50-about 600 mg of the IL-4R inhibitor.
12 . The method of claim 11 , wherein each secondary dose comprises about 25-about 400 mg of the IL-4R inhibitor.
13 . The method of claim 10 , wherein the initial dose comprises about 600 mg of the IL-4R inhibitor, and each secondary dose comprises about 300 mg of the IL-4R inhibitor.
14 . The method of claim 13 , wherein each secondary dose is administered one week after the immediately preceding dose.
15 . The method of claim 13 , wherein each secondary dose is administered 2 weeks after the immediately preceding dose.
16 - 18 . (canceled)
19 . The method of claim 1 , wherein the IL-4R inhibitor is administered subcutaneously.
20 . The method of claim 1 , wherein the IL-4R 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 topical corticosteroids, calcineurin inhibitors, and emollients.
21 . The method of claim 20 , wherein the IL-4R inhibitor is administered in combination with a topical corticosteroid (TCS).
22 . The method of claim 21 , wherein the TCS is a low-potency TCS or a medium-potency TCS.
23 - 28 . (canceled)
29 . 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.
30 . 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.
31 . The method of claim 1 , wherein the IL-4R inhibitor is dupilumab or a bioequivalent thereof.
32 - 47 . (canceled)