Methods of treating ankylosing spondylitis using IL-17 antagonists
The disclosure relates to novel regimens for treating an inflammatory arthritis, e.g., rheumatoid arthritis (RA) patients, e.g., high risk RA patients, which employ a therapeutically effective amount of an IL-17 antagonist, e.g., 1L-1 7 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof).
1. A method of treating ankylosing spondylitis (AS), comprising:
a) subcutaneously administering to a patient having AS five doses of about 150 mg of an IL-17 antibody, each of the five doses being delivered weekly; and
b) thereafter, subcutaneously administering a dose of about 150 mg of the IL-17 antibody to the patient every month, beginning one month from the fifth subcutaneous dose according to step a),
wherein the IL-17 antibody binds to an epitope of the human IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ile127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL-17 antibody has a K D of about 100-200 pM, and wherein the IL-17 antibody has an in vivo half-life of about 4 weeks.
2. A method of treating AS, comprising:
a) subcutaneously administering to a patient in need thereof five doses of about 150 mg of an IL-17 antibody, each of the five doses being delivered weekly; and
b) thereafter, subcutaneously administering to the patient a dose of about 150 mg of the IL-17 antibody every month;
wherein the IL-17 antibody comprises:
i) an immunoglobulin V H domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin V L domain comprising the amino acid sequence set forth as SEQ ID NO: 10;
ii) an immunoglobulin V H domain comprising the hypervariable regions comprising the amino acid sequences set forth as SEQ ID NO:1-3, respectively; and an immunoglobulin V L domain comprising the hypervariable regions comprising the amino acid sequences set forth as SEQ ID NO:4-6, respectively; or
iii) an immunoglobulin V H domain comprising the hypervariable regions comprising the amino acid sequences set forth as SEQ ID NO:11-13, respectively; and an immunoglobulin V L domain comprising the hypervariable regions comprising the amino acid sequences set forth as SEQ ID NO:4-6, respectively.
3. The method according to any one of claim 1 or 2 , wherein the IL-17 antibody is secukinumab.
4. The method according to claim 3 , wherein, prior to treatment with the IL-17 antibody, the patient had an inadequate response to, had failure to, or was intolerant to treatment with a TNF alpha antagonist.
5. A method of treating active AS, comprising administering about 150 mg secukinumab by subcutaneous injection to a patient in need thereof at weeks 0, 1, 2, 3 and 4, and then monthly thereafter.
6. The method according to claim 5 , wherein the patient has moderate to severe active AS.
7. The method according to claim 5 , further comprising administering an NSAID, methotrexate, sulphasalazine, or prednisolone to the patient.
8. The method according to claim 5 , wherein the patient previously had an inadequate response to at least one NSAID.
9. The method according to claim 5 , wherein the patient is a DMARD failure.
10. A method of treating active AS, comprising administering about 150 mg secukinumab by subcutaneous injection to a patient in need thereof at weeks 0, 1, 2, 3 and 4, followed by 150 mg every 4 weeks.
11. A method of treating active AS in a patient who has responded inadequately to previous treatment with at least one NSAID, comprising administering about 150 mg of secukinumab by subcutaneous injection to the patient at weeks 0, 1, 2, 3 and 4, followed by 150 mg every 4 weeks.
12. The method according to any one of claims 1 , 2 , 5 , 6 , 8 , 9 , 7 , 10 and 11 , wherein, prior to treatment with the IL-17 antibody, the patient had an inadequate response to, had failure to, or was intolerant to treatment with a TNF alpha antagonist.