Methods and compositions for treating subjects having rheumatoid arthritis

Abstract

Disclosed herein are methods for treating subjects having rheumatoid arthritis (RA) with a human anti-interleukin 6 (IL-6) antibody, or antigen-binding portion thereof.

1 . A method for treating a subject selected from the group consisting of
 (a) determining the level of interleukin 6 (IL-6) in a sample(s) obtained from a subject having rheumatoid arthritis (RA)subject, and   administering to the subject a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody or antigen-binding portion thereof if the level of IL-6 in the subject sample(s) is determined to be a high IL-6 level, thereby treating the subject;   (b) selecting a subject having high interleukin 6 rheumatoid arthritis (high IL-6RA), and   administering to the subject a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof, thereby treating the subject;   (c) administering to a subject previously identified as having high interleukin 6 rheumatoid arthritis (high TL-6RA) a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof, thereby treating the subject;   (d) determining whether a subject suspected of having rheumatoid arthritis (RA) has high interleukin 6 rheumatoid arthritis (high IL-6RA), and   administering to the subject a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof, thereby treating the subject;   (e) selecting a subject having rheumatoid arthritis previously treated with adalimumab or a biosimilar of adalimumab, who has or presented with high IL-6 levels, and had an inadequate response to adalimumab or a biosimilar of adalimumab,   discontinuing adalimumab treatment for the patient, and   initiating a therapeutic regimen for the patient comprising one or more doses of sarilumab,   thereby treating the subject;   (f) determining whether a methotrexate-intolerant subject having rheumatoid arthritis (RA) has high interleukin 6 rheumatoid arthritis (high TL-6RA), and   administering to the subject a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof, thereby treating the subject;   (g) determining whether a methotrexate-inadequate responder subject has high interleukin 6 rheumatoid arthritis (high IL-6RA), and   administering to the subject a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof, thereby treating the subject; and   (h) determining the level of interleukin 6 (IL-6) in a sample(s) from a subject having rheumatoid arthritis so that the subject is determined to belong to either a first category of rheumatoid arthritis disease severity or a second category of rheumatoid arthritis disease severity;   assigning a therapy to the subject if the subject is associated with the first category of rheumatoid arthritis disease severity, wherein the therapy is administration of a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof, and   administering the human IL-6R antibody, or antigen-binding portion thereof, to the subject,   thereby treating the subject having rheumatoid arthritis.   
     
     
         2 . A method for treating subjects having rheumatoid arthritis, the method comprising the steps of:
 determining the level of interleukin 6 (IL-6) in serum samples from the subjects so that each subject is determined to belong to either a first category of rheumatoid arthritis disease severity or a second category of rheumatoid arthritis disease severity;   assigning a therapy to the subjects in the first category of rheumatoid arthritis disease severity, wherein the therapy is administration of a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof, and   administering the human IL-6R antibody, or antigen-binding portion thereof, to the subjects in the first category of rheumatoid arthritis disease severity,   thereby treating the subjects having rheumatoid arthritis.   
     
     
         3 . The method of  claim 2 , wherein the first category of rheumatoid arthritis disease severity corresponds to a high level of IL-6. 
     
     
         4 . The method of  claim 2 , wherein the second category of rheumatoid arthritis disease severity corresponds to a moderate level of IL-6 and/or a low level of IL-6. 
     
     
         5 . The method of  claim 1 , wherein the subject is suspected of having RA. 
     
     
         6 . The method of  claim 5 , wherein the subject is suspected of having rheumatoid arthritis and the method further comprises determining whether the subject has high IL-6RA. 
     
     
         7 . The method of  claim 1 , wherein the subject was previously diagnosed as having RA. 
     
     
         8 . The method of  claim 1 , wherein the subject is a treatment naïve RA subject or has previously been administered one or more therapeutic agents for treating RA. 
     
     
         9 . The method of  claim 1 , wherein the subject sample(s) is a fluid sample. 
     
     
         10 . The method  claim 1  or  2 , wherein the anti-IL6R antibody, or antigen-binding portion thereof, is a fully human anti-IL6R antibody, or antigen-binding portion thereof. 
     
     
         11 . The method of  claim 10 , wherein the anti-IL6R antibody, or antigen-binding portion thereof, comprises heavy and light chain CDR sequences from a HCVR/LCVR sequence pair selected from the group consisting of SEQ ID NOs: 3/11; 227/229; 19/27; 231/233; 35/43; 51/59; 67/75; 83/91; 99/107; 115/123; 131/139; 147/155; 239/155; 241/155; 163/171; 179/187; 235/237; 195/203; and 211/219. 
     
     
         12 . The method of  claim 11  wherein the anti-IL6R antibody, or antigen-binding portion thereof, comprises three heavy chain complementarity determining region (HCDR) sequences comprising SEQ ID NOs:21, 23, 25, respectively, and three light chain complementarity determining (LCDR) sequences comprising SEQ ID NOs: 29, 31, 33, respectively. 
     
     
         13 . The method of  claim 1  or  2  and, wherein the anti-IL6R antibody, or antigen-binding portion thereof, is administered to the subject in a pharmaceutical composition. 
     
     
         14 . The method of  claim 13 , wherein the pharmaceutical composition is present in a pre-filled syringe. 
     
     
         15 . A kit for the treatment of rheumatoid arthritis, comprising
 an anti-IL-6 diagnostic antibody;   an anti-IL-6R therapeutic antibody; and   written instructions instructing a medical professional to administer the anti-IL-6R therapeutic antibody to the patient as first-line therapy if the patient exhibits high IL-6 levels as determined with the anti-IL 6 diagnostic antibody.