Antibodies neutralizing GM-CSF for use in the treatment of rheumatoid arthritis or as analgesics

1. A method of treating an inflammatory disease, wherein the inflammatory disease is rheumatoid arthritis (RA), in a human subject, comprising administering to the human subject a neutralizing antibody or a functional fragment thereof that specifically binds a primate granulocyte macrophage colony-stimulating factor (GM-CSF),

wherein the neutralizing antibody or functional fragment thereof is administered according to the following dosing scheme:

i) administering a first initial dose to the human subject;

ii) administering a second dose to the human subject about 14 days after the first initial dose;

iii) administering a third dose to the human subject about 28 days after the second dose; and

iv) administering one or more additional doses to the human subject with intervals of about 28 days beginning about 28 days after the third dose;

wherein the neutralizing antibody or functional fragment thereof comprises a light chain variable region and a heavy chain variable region, wherein the light chain variable region comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 16, a CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 18, and wherein the heavy chain variable region comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 14, a CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 2.

2. The method of claim 1 , wherein the light chain variable region comprises the amino acid sequence of SEQ ID NO: 19, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 21.

3. The method of claim 1 , wherein the light chain comprises the amino acid sequence of SEQ ID NO: 34 and heavy chain comprises the amino acid sequence of SEQ ID NO: 35.

4. The method of claim 1 , wherein each dose has a quantity of 10 to 50 mg, 25 to 100 mg, or 50 to 300 mg of the neutralizing antibody or functional fragment thereof.

5. The method of claim 4 , wherein the antibody or functional fragment thereof is formulated for subcutaneous administration.

6. The method of claim 1 , wherein each dose has a quantity of 20 mg, 80 mg, or 150 mg of the neutralizing antibody or functional fragment thereof.

7. The method of claim 1 , wherein the neutralizing antibody or functional fragment thereof is administered subcutaneously.

8. The method of claim 1 , wherein the neutralizing antibody or functional fragment thereof is administered subcutaneously in at least 5 or at least 7 doses over a period of at least 21 weeks.

9. The method of claim 1 , wherein structural joint damage does not advance for at least 1 year subsequent to the start of treatment.

10. The method of claim 1 , wherein the disease activity score (DAS28CRP) is reduced to <3.2 at least 12 weeks after the start of treatment.

11. The method of claim 1 , wherein the human subject receives at least one additional anti-inflammatory drug selected from the group consisting of DMARDs, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDS), opioids, and biologic drugs.

12. The method of claim 11 , wherein the at least one additional anti-inflammatory drug is an anti-folate compound.

13. The method of claim 12 , wherein the anti-folate compound is methotrexate.

14. The method of claim 13 , wherein the methotrexate is administered once weekly.

15. The method of claim 14 , wherein the methotrexate is administered at a dose of 7.5 to 25 mg per administration.

16. The method of claim 11 , wherein the antibody or functional fragment thereof is formulated for subcutaneous administration.

17. The method of claim 1 , wherein the human subject suffers from moderate, moderate to severe or severe rheumatoid arthritis.

18. The method of claim 1 , wherein the human subject has moderate, moderate to severe, or severe rheumatoid arthritis that is insufficiently controlled by:

i) treatment with methotrexate for at least 3 months;

ii) treatment with a DMARD selected from the group consisting of sulfasalazine, leflunomide and hydroxychloroquine for at least 3 months;

iii) treatment with methotrexate in combination with another non-biologic DMARD for at least 3 months; or

iv) treatment with methotrexate in combination a biologic DMARD for at least 3 months.

19. The method of claim 1 , wherein the human subject is selected from the group consisting of:

a) patients who have not previously been treated for RA; and

b) patients who have been treated for RA, wherein:

i) the patients have received a DMARD, a glucocorticoid, or a combination thereof;

ii) the patients have received a non-biologic DMARD treatment, but have not received a biologic DMARD treatment (biologic treatment naive);

iii) the patients have received a biologic treatment in combination with methotrexate or other non-biologic DMARD;

iv) the patients have received methotrexate for at least 3 months and have further received folinic acid or folic acid on the days after methotrexate administration;

v) the patients have been treated with methotrexate, but have not been co-treated with an adenosine receptor antagonist selected from the group consisting of theophylline and caffeine;

vi) the patients have been treated with methotrexate and have a genetic polymorphism in at least one of the thymidylate synthase gene, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase gene, and reduced folate carrier (RFCI) gene; or

vii) the patients have been treated with weekly doses of methotrexate at 7.5-25 mg per week and do not have signs of neutropenia for at least 12 weeks after initial administration of methotrexate.