Methods for treating il-6 mediated inflammation without immunosuppression

Abstract

The disclosure provides methods of treating inflammation without inducing immune suppression. The method comprises administering a therapeutically effective amount of an IL-6 antagonist at a dose sufficient to reduce inflammation without causing immune suppression.

What is claimed is: 
     
         1 . A method of treating a patient who has KDOQI stage 3-5 chronic kidney disease (CKD) with inflammation to reduce the risk of cardiovascular morbidity and mortality, comprising:
 administering an IL-6 antagonist to a patient with KDOQI stage 3-5 CKD and a CRP level greater than 2 mg/L at a dose that is sufficient to reduce the CRP level to 2 mg/L or less and reduce the risk of cardiovascular morbidity and mortality.   
     
     
         2 . The method of  claim 1 , wherein the IL-6 antagonist is administered at a dose that is sufficient to reduce the risk of heart failure and/or cardiovascular death. 
     
     
         3 . The method of  claim 1 , wherein the IL-6 antagonist is administered at a dose that is sufficient to reduce nonfatal myocardial infarction and/or nonfatal stroke. 
     
     
         4 . The method of  claim 1 , wherein the IL-6 antagonist is administered at a dose that is sufficient to increase cardiac function. 
     
     
         5 . The method of  claim 1 , wherein the IL-6 antagonist is administered at a dose that is sufficient to reduce fibrosis after acute myocardial infarction. 
     
     
         6 . The method of  claim 1 , wherein the IL-6 antagonist is administered at a dose that does not cause immune suppression. 
     
     
         7 . The method of  claim 6 , wherein the immune suppression is measured by absolute neutrophil count (ANC). 
     
     
         8 . The method of  claim 7 , wherein the post-treatment ANC is at least 1500 cells/μL. 
     
     
         9 . The method of  claim 1 , wherein the post-treatment LDL level is increased by no more than 10% as compared to pre-treatment levels. 
     
     
         10 . The method of  claim 1 , wherein the IL-6 antagonist is administered at a monthly equivalent dose that is no more than 30% of the monthly equivalent dose for treating rheumatoid arthritis with the same IL-6 antagonist. 
     
     
         11 . The method of  claim 1 , wherein the IL-6 antagonist is an anti-IL-6 antibody or an anti-IL-6R antibody. 
     
     
         12 . The method of  claim 11 , wherein the anti-IL-6 antibody or the anti-IL-6R antibody is selected from the group consisting of: COR-001, siltuximab, gerilimzumab, sirukumab, clazakizumab, olokizumab, VX30 (VOP-R003; Vaccinex), EB-007 (EBI-029; Eleven Bio), FM101 (Femta Pharmaceuticals, Lonza), tocilizumab, sarilumab, and vobarilizumab. 
     
     
         13 . The method of  claim 12 , wherein the anti-IL-6 antibody is COR-001. 
     
     
         14 . The method of  claim 13 , wherein COR-001 is administered intravenously at a monthly equivalent dose of 2-40 mg. 
     
     
         15 . The method of  claim 13 , wherein COR-001 is administered subcutaneously at a monthly equivalent dose of 3-70 mg. 
     
     
         16 . A method of treating a patient who has atherosclerotic cardiovascular disease with inflammation to reduce the risk of cardiovascular morbidity and mortality, comprising:
 administering an IL-6 antagonist to a patient with atherosclerotic cardiovascular disease and a CRP level greater than 2 mg/L at a dose that is sufficient to reduce the CRP level to 2 mg/L or less and reduce the risk of cardiovascular morbidity and mortality.   
     
     
         17 . The method of  claim 16 , wherein the IL-6 antagonist is administered at a dose that is sufficient to reduce the risk of heart failure and/or cardiovascular death. 
     
     
         18 . The method of  claim 16 , wherein the IL-6 antagonist is administered at a dose that is sufficient to reduce nonfatal myocardial infarction and/or nonfatal stroke. 
     
     
         19 . The method of  claim 16 , wherein the IL-6 antagonist is administered at a dose that is sufficient to increase cardiac function. 
     
     
         20 . The method of  claim 16 , wherein the IL-6 antagonist is administered at a dose that is sufficient to reduce fibrosis after acute myocardial infarction. 
     
     
         21 . The method of  claim 16 , wherein the IL-6 antagonist is administered at a dose that does not cause immune suppression. 
     
     
         22 . The method of  claim 21 , wherein the immune suppression is measured by absolute neutrophil count (ANC). 
     
     
         23 . The method of  claim 22 , wherein the post-treatment ANC is at least 1500 cells/μL. 
     
     
         24 . The method of  claim 16 , wherein the post-treatment LDL level is increased by no more than 10% as compared to pre-treatment levels. 
     
     
         25 . The method of  claim 16 , wherein the IL-6 antagonist is administered at a monthly equivalent dose that is no more than 30% of the monthly equivalent dose for treating rheumatoid arthritis with the same IL-6 antagonist. 
     
     
         26 . The method of  claim 16 , wherein the IL-6 antagonist is an anti-IL-6 antibody or an anti-IL-6R antibody. 
     
     
         27 . The method of  claim 26 , wherein the anti-IL-6 antibody or the anti-IL-6R antibody is selected from the group consisting of: COR-001, siltuximab, gerilimzumab, sirukumab, clazakizumab, olokizumab, VX30 (VOP-R003; Vaccinex), EB-007 (EBI-029; Eleven Bio), FM101 (Femta Pharmaceuticals, Lonza), tocilizumab, sarilumab, and vobarilizumab. 
     
     
         28 . The method of  claim 27 , wherein the anti-IL-6 antibody is COR-001. 
     
     
         29 . The method of  claim 28 , wherein COR-001 is administered intravenously at a monthly equivalent dose of 2-40 mg. 
     
     
         30 . The method of  claim 28 , wherein COR-001 is administered subcutaneously at a monthly equivalent dose of 3-70 mg.