Methods for treatment of inflammatory disease or IL-6-mediated condition with gp130 protein
A selective IL-6-trans-signalling inhibitor can be used to treat a variety of IL-6-mediated conditions, including inflammatory diseases and cancer. The inhibitor can safely be administered to humans at a variety of doses. Moreover, the inhibitor lessens deleterious effects associated with other IL-6 inhibitors such as lowering neutrophil counts, platelet counts and levels of C-reactive protein.
1. A method for the treatment of an inflammatory disease or an IL-6- mediated condition in a human, said method comprising administering to a human in need thereof an effective amount of a polypeptide dimer that inhibits IL-6 trans-signaling, wherein the polypeptide dimer comprises two monomers, each monomer comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1, and comprises the gp130 D6 domain corresponding to the amino acids at positions 585-595 of SEQ ID NO: 1, and an Fc domain hinge region comprising the amino acids at positions 609-612 of SEQ ID NO: 1, and each monomer does not comprise a linker between the gp130 D6 domain and the Fc domain hinge region; wherein the effective amount is 60 mg to 750 mg of the polypeptide dimer; and wherein the polypeptide dimer is administered every 7-60 days.
2. The method of claim 1 , wherein each monomer comprises the amino acid sequence of SEQ ID NO: 1.
3. The method of claim 1 , wherein the effective amount is 60 mg to 600 mg.
4. The method of claim 1 , wherein the polypeptide dimer is administered every 7-30 days.
5. The method of claim 4 , wherein the polypeptide dimer is administered every 7-20 days.
6. The method of claim 1 , wherein the polypeptide dimer is administered every 7-14 days.
7. The method of claim 1 , wherein the polypeptide dimer is administered every 7 days.
8. The method of claim 1 , wherein the polypeptide dimer is administered every 14 days.
9. The method of claim 1 , wherein the polypeptide dimer is administered parenterally.
10. The method of claim 1 , wherein the polypeptide dimer is administered intravenously or subcutaneously.
11. The method of claim 1 , wherein the inflammatory disease or IL-6-mediated condition is inflammatory bowel disease.
12. The method of claim 11 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
13. The method of claim 11 , wherein the treatment induces or maintains the remission of inflammatory bowel disease.
14. The method of claim 1 , wherein the inflammatory disease or IL-6-mediated condition is rheumatoid arthritis, psoriasis, uveitis or atherosclerosis.
15. The method of claim 1 , wherein neutrophil counts, platelet counts and/or levels of C-reactive protein are maintained within a physiologically normal range after administration of the polypeptide dimer.
16. The method of claim 1 , wherein the treatment further comprises the administration of a second active agent.
17. The method of claim 16 , wherein the second active agent is 5-aminosalicylic acid, azathioprine, 5-mercaptopurine or a corticosteroid.