Methods for treating or preventing asthma by administering an il-4r antagonist

A method for treating a subject having severe uncontrolled asthma comprising:

• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein the plurality of maintenance doses are administered during a treatment phase comprising an induction phase, an oral corticosteroid (OCS) reduction phase, and a maintenance phase, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;1 or
• a method for treating a subject having severe uncontrolled asthma comprising:
• administering to the subject 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);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof, wherein each maintenance dose is about 300 mg of the antibody or antigen-binding fragment thereof,
• wherein the plurality of maintenance doses is administered during a treatment phase comprising an induction phase, an oral corticosteroid (OCS) reduction phase, and a maintenance phase, and
• wherein the antibody or antigen-binding fragment thereof comprises heavy and light chain CDR sequences from the HCVR/ LCVR sequence pair comprising SEQ ID NOs:
• 1 and 2;
• or
• a method for improving an FEVi score in a subject having moderate-to-severe uncontrolled asthma, comprising administering to the subject q2w or q4w an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R such that the subject exhibits an improvement in FEV1 score at week 4, week 12 or week 24 following administration of the antibody or antigen binding fragment, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or
• a method for improving a forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75) score in a subject having moderate-to-severe uncontrolled asthma, comprising administering to the subject q2w or q4w an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R, such that the subject exhibits an improvement in FEF25-75 score at week 4 or week 24 following administration of the antibody or antigen binding fragment, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or
• a method for reducing an annualized severe exacerbation rate in a subject having moderate-to-severe uncontrolled asthma, comprising administering to the subject q2w or q4w an antibody or an antigen-binding fragment thereof that specifically binds to IL-4R, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or
• a method of reducing or eliminating oral corticosteroid (OCS) use in a subject suffering from steroid dependent severe asthma, the method comprising
• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein a reduction of at least 50% in OCS use is achieved at week 24 following administration of the loading dose, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or
• a method for treating a subject having oral corticosteroid (OCS)-dependent, moderate-to-severe asthma comprising:
• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein the loading dose and the plurality of maintenance doses are administered as an add-on maintenance asthma therapy, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or
• a method for improving asthma control in a subject having oral corticosteroid-dependent asthma comprising:
• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof, and
• wherein the loading dose and the plurality of maintenance doses are administered as an add-on maintenance asthma therapy, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or
• a method for treating a subject having moderate-to-severe uncontrolled asthma wherein onset of asthma occurred when the subject was greater than 40 years of age comprising:
• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein the loading dose and the plurality of maintenance doses are administered as an add-on maintenance asthma therapy, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or
• a method for treating a subject having moderate-to-severe uncontrolled asthma and one or both of co-morbid chronic rhinosinusitis and nasal polyposis comprising:
• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein the loading dose and the plurality of maintenance doses are administered as an add-on maintenance asthma therapy, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively.

A method for treating a subject having oral corticosteroid-dependent asthma or moderate-to-severe asthma and co-morbid moderate-to-severe atopic dermatitis comprising:

• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein the loading dose and the plurality of maintenance doses are administered as an add-on maintenance asthma therapy, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively.

A method for treating a subject having moderate-to-severe uncontrolled asthma and co-morbid allergic rhinitis comprising:

• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein the loading dose and the plurality of maintenance doses are administered as an add-on maintenance asthma therapy, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or
• a method for improving allergic rhinitis-related quality of life of a subject having moderate-to-severe uncontrolled asthma and co-morbid allergic rhinitis comprising:
• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein the loading dose and the plurality of maintenance doses are administered as an add-on maintenance asthma therapy, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively;
• or p1 a method for improving allergic rhinitis-related quality of life in a subject having oral corticosteroid-dependent asthma comprising:
• administering to the subject a loading dose of an antibody or an antigen-binding fragment thereof that specifically binds to interleukin-4 receptor (IL-,4R);
• and
• administering to the subject a plurality of maintenance doses of the antibody or the antigen-binding fragment thereof,
• wherein the loading dose and the plurality of maintenance doses are administered as an add-on maintenance asthma therapy, and
• wherein the antibody or antigen-binding fragment thereof comprises three heavy chain CDR sequences comprising SEQ ID NOs:
• 3, 4, and 5, respectively, and three light chain CDR sequences comprising SEQ ID NOs:
• 6, 7, and 8, respectively.