Compositions and methods for treating polymyalgia rheumatica by administering an IL-6R antagonist

Abstract

To provide a composition for treating polymyalgia rheumatica (PMR) with reduced harmful side effects.SOLUTION: The present disclosure relates to an antibody or an antigen-binding fragment thereof that specifically binds to an IL-6 receptor, wherein the antibody or the antigen-binding fragment thereof is used in a method for treating polymyalgia rheumatica (PMR) in a subject in need of treatment for PMR.SELECTED DRAWING: None

Claims

1. A pharmaceutical composition for treating polymyalgia rheumatica (PMR) in subjects requiring treatment for PMR, wherein the pharmaceutical composition comprises an antibody or antigen-binding fragment that specifically binds to the interleukin-6 receptor (IL-6R), wherein the antibody or antigen-binding fragment comprises a heavy chain containing the amino acid sequence of SEQ ID NO: 9 and a light chain containing the amino acid sequence of SEQ ID NO:

10.

2. The pharmaceutical composition according to claim 1, wherein the antibody is sarilumab.

3. The subject is the pharmaceutical composition according to claim 1, which has had an insufficient response to a previous PMR treatment.

4. The pharmaceutical composition according to claim 1, wherein the subject has at least one episode of apparent PMR flare while attempting to gradually reduce corticosteroids.

5. The pharmaceutical composition according to claim 1, wherein the subject has previously been administered a prednisone equivalent dose of corticosteroid at a dose of at least 7.5 mg / day, and not exceeding 25 mg / day, and in some cases not exceeding 20 mg / day.

6. The pharmaceutical composition according to claim 1, wherein the antibody or its antigen-binding fragment is administered in combination with a further therapeutic agent.

7. The pharmaceutical composition according to claim 6, wherein the further therapeutic agent comprises a corticosteroid.

8. The pharmaceutical composition according to claim 6, wherein the further therapeutic agent includes a corticosteroid tapering.

9. The pharmaceutical composition according to claim 8, wherein the corticosteroid is gradually reduced over a period of at least 14 weeks, and / or the corticosteroid is gradually reduced to a prednisone equivalent dose of 2.5 mg or less per day or 2 mg or less per day.

10. The pharmaceutical composition according to claim 9, wherein the dose of corticosteroid administered at the start of treatment with the antibody or its antigen-binding fragment is approximately 15 mg / day of prednisone equivalent dose.

11. The pharmaceutical composition according to claim 9, wherein the dose of corticosteroids is reduced or eliminated for at least 52 weeks.

12. The pharmaceutical composition according to claim 9, wherein the antibody or its antigen-binding fragment is continued for the target PMR treatment even after the dose of corticosteroids has been reduced or discontinued.

13. The pharmaceutical composition according to any one of claims 4, 5, and 7 to 12, wherein the corticosteroid comprises prednisone.

14. The pharmaceutical composition according to claim 1, wherein the subject has previously been administered a conventional disease-modifying antirheumatic drug (cDMAD) different from the antibody or its antigen-binding fragment.

15. The subject is the pharmaceutical composition according to claim 1, wherein a cDMAD different from the antibody or its antigen-binding fragment is administered simultaneously.

16. The pharmaceutical composition according to claim 14 or 15, wherein the cDMARD is selected from methotrexate, azathioprine, and leflunomide.

17. The pharmaceutical composition according to claim 14 or 15, wherein cDMARD is methotrexate.

18. The pharmaceutical composition according to any one of claims 1 to 12, 14, and 15, wherein the subject has at least one symptom selected from the following: shoulder pain with inflammatory stiffness; hip pain with inflammatory stiffness; elevated C-reactive protein (CRP) levels; and elevated erythrocyte sedimentation rate (ESR), and combinations thereof, prior to administration of the antibody or its antigen-binding fragment.

19. (i) At least one symptom of PMR in the subject improves after treatment with an antibody or an antigen-binding fragment thereof, the at least one symptom being selected from shoulder pain with inflammatory stiffness, hip pain with inflammatory stiffness, elevated C-reactive protein (CRP) levels, elevated erythrocyte sedimentation rate (ESR) and / or a combination thereof, and / or (ii) A pharmaceutical composition according to any one of claims 1 to 12, 14 and 15, wherein at least one patient-reported outcome measure or clinician-reported outcome measure improves after treatment with an antibody or its antigen-binding fragment, and the at least one patient-reported outcome measure or clinician-reported outcome measure is selected from the Functional Assessment of Chronic Disease Therapy and Fatigue Scale (FACIT-Fatigue), the EuroQol 5-Item 3-Level Questionnaire (EQ-5D-3L), the Short Form-36v2 (SF-36v2) Questionnaire, the Health Assessment Questionnaire Disability Index (HAQ-DI), and the Physician's Global Assessment of Disease Activity-Visual Analog Scale (MD-VAS), and combinations thereof.

20. The pharmaceutical composition according to any one of claims 1 to 12, 14, and 15, wherein the antibody or its antigen-binding fragment is administered in a dose of about 150 mg to about 200 mg.

21. The antibody or its antigen-binding fragment is administered once every two weeks at a dose of approximately 150 mg. A pharmaceutical composition according to any one of items 1 to 12, 14, and 15.

22. The pharmaceutical composition according to any one of claims 1 to 12, 14, and 15, wherein the antibody or its antigen-binding fragment is administered once every two weeks in a dose of about 200 mg.

23. The pharmaceutical composition according to claim 21, wherein the antibody or its antigen-binding fragment is administered subcutaneously.

24. The pharmaceutical composition according to claim 22, wherein the antibody or its antigen-binding fragment is administered subcutaneously.

25. The pharmaceutical composition according to any one of claims 1 to 12, 14, and 15, wherein the pharmaceutical composition is administered subcutaneously using a needle and syringe, a pen-type delivery device, or an autoinjector.

26. The pharmaceutical composition according to any one of claims 1 to 12, 14, and 15, wherein treatment with an antibody or its antigen-binding fragment results in sustained remission of PMR for at least 52 weeks after the start of treatment.

27. ​​Treatment with an antibody or its antigen-binding fragment is as follows: (i) A decrease in the glucocorticoid toxicity index (GTI) score of the target group. (ii) A decrease in the target PMR activity score (PMR-AS), (iii) Increase in the time to the first PMR flare in the target, (iv) Remission of PMR in the subject, and, if applicable, the subject has no disease flare during the remission period in the subject, (v) Resolution of at least one sign and symptom of PMR in the subjects, or resolution of at least one sign and symptom of PMR without glucocorticoid (GC) A pharmaceutical composition according to any one of claims 1 to 12, 14, and 15, which provides at least one of the following.

28. (i) A subject having PMR is seronegative for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), (ii) Subjects do not have a disorder or disease selected from giant cell arteritis, rheumatoid arthritis, inflammatory arthritis, connective tissue disease, rhabdomyolysis, neuropathic muscle disease, and active fibromyalgia, and / or (iii) The pharmaceutical composition according to any one of claims 1 to 12, 14 and 15, wherein the subject does not have a connective tissue disease selected from systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease and ankylosing spondylitis.

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