Methods for Treating Atopic Dermatitis by Administering an IL-4R Antagonist
The present invention provides methods for treating atopic dermatitis (AD). Also provided are methods for improving one or more AD-associated parameter(s), and methods for decreasing the level of at least one AD-associated biomarker in a subject in need thereof. The methods of the present invention comprise administering to a subject in need thereof a pharmaceutical composition comprising an interleukin-4 receptor (IL-4R) antagonist such as an anti-IL-4R antibody.
1 . A method for reducing pruritus associated with atopic dermatitis (AD) in a patient, the method comprising:
(a) selecting a patient with moderate-to-severe atopic dermatitis, wherein the patient exhibits a Pruritus Numeric Rating Scale (NRS) score ≧5 and/or a 5-D Pruritus score ≧18; and
(b) administering to the patient one or more doses of a pharmaceutical composition comprising a therapeutically effective amount of an anti-interleukin-4-receptor (IL-4R) antibody or antigen-binding fragment thereof;
wherein the antibody or antigen-binding fragment thereof comprises heavy and light chain complementarity determining regions (CDRs) in a heavy chain variable region/light chain variable region (HCVR/LCVR) amino acid sequence pair comprising SEQ ID NOs: 162/164.
2 . The method of claim 1 , wherein the patient is resistant, inadequately responsive or intolerant to topical corticosteroids or topical calcineurin inhibitors.
3 . The method of claim 1 , wherein the patient has a history of side effects or safety risks associated with topical corticosteroids or topical calcineurin inhibitors.
4 . The method of claim 1 , wherein the patient, following administration of the pharmaceutical composition, exhibits reduced pruritus as measured by a decrease from baseline in NRS score of at least 30%; and/or a decrease from baseline in 5-D Pruritus score of at least 30%.
5 . The method of claim 4 , wherein the patient, following administration of the pharmaceutical composition exhibits an improvement in at least one AD-associated parameter selected from the group consisting of:
(i) a decrease from baseline in Investigator's Global Assessment (IGA) score of at least 25%;
(ii) a decrease from baseline in Eczema Area and Severity Index (EASI) score of at least 50%;
(iii) a decrease from baseline in SCORing Atopic Dermatitis (SCORAD) score of at least 30%; and
(iv) a decrease from baseline in Body Surface Area Involvement of Atopic Dermatitis (BSA) score of at least 25%.
6 . The method of claim 5 , wherein the improvement comprises a decrease from baseline in IGA score to achieve an IGA score of 0 or 1 by week 16 after administration of the first dose of the pharmaceutical composition.
7 . The method of claim 5 , wherein the improvement comprises an IGA score reduction of ≧2 by week 16 after administration of the first dose of the pharmaceutical composition.
8 . The method of claim 5 , wherein the improvement comprises a decrease from baseline in IGA of at least 30% on day 29 after administration of the first dose of the pharmaceutical composition.
9 . The method of claim 5 wherein the improvement comprises a decrease from baseline in NRS of at least 40% on day 29 after administration of the first dose of the pharmaceutical composition.
10 . The method of claim 5 , wherein the improvement comprises a decrease from baseline in EASI of at least 60% on day 29 after administration of the first dose of the pharmaceutical composition.
11 . The method of claim 5 , wherein the improvement comprises a decrease from baseline in SCORAD of at least 40% on day 29 after administration of the first dose of the pharmaceutical composition.
12 . The method of claim 5 , wherein the improvement comprises a decrease from baseline in 5-D Pruritus score of at least 35% on day 29 after administration of the first dose of the pharmaceutical composition.
13 . The method of claim 5 , wherein the improvement comprises a decrease from baseline in BSA score of at least 35% on day 29 after administration of the first dose of the pharmaceutical composition.
14 . The method of claim 5 , wherein the improvement comprises a decrease from baseline in EASI score of 75% by week 16 after administration of the first dose of the pharmaceutical composition.
15 . The method of claim 1 , wherein each dose of the pharmaceutical composition comprises about 50 to about 600 mg of the anti-IL-4R antibody or antigen-binding fragment thereof.
16 . The method of claim 1 , wherein each dose of the pharmaceutical composition comprises about 300 mg of the anti-IL-4R antibody or antigen-binding fragment thereof.
17 . The method of claim 1 , wherein step (b) comprises: administering an initial dose of the pharmaceutical composition to the patient; followed by administering one or more subsequent doses of the pharmaceutical composition to the patient.
18 . The method of claim 17 , wherein the initial dose comprises about 600 mg of the anti-IL-4R antibody or antigen-binding fragment thereof; and wherein each subsequent dose comprises about 300 mg of the anti-IL-4R antibody or antigen-binding fragment thereof.
19 . The method of claim 18 , wherein each subsequent dose is administered to the patient one week after the immediately preceding dose.
20 . The method of claim 18 , wherein each subsequent dose is administered to the patient two weeks after the immediately preceding dose.
21 . The method of claim 1 , wherein step (b) further comprises concomitantly administering topical corticosteroids daily for up to 28 days.
22 . The method of claim 21 , wherein the daily amount of topical corticosteroids used by the patient is gradually reduced following administration of the first dose of the pharmaceutical composition.
23 . The method of claim 22 , wherein the daily amount of topical corticosteroids used by the patient is reduced by about 20% to about 50% over 4 weeks following administration of the first dose of the pharmaceutical composition.
24 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDRs (HCDRs) comprising SEQ ID NOs: 148, 150 and 152, respectively, and three light chain CDRs (LCDRs) comprising SEQ ID NOs: 156, 158 and 160, respectively.