Treatment of inflammatory conditions by delivery of interleukin-1 receptor antagonist fusion protein

Abstract

The present invention provides, among other things, methods of treating post-cardiac injury syndrome (PCIS) or pericarditis, comprising a step of administering to a subject in need of treatment an interleukin-1 receptor-Fc fusion protein at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce one or more signs and symptoms of pericarditis relative to a control.

1 . A method of treating post-cardiac injury syndrome (PCIS) comprising a step of administering to a subject in need of treatment an interleukin-1 receptor-Fc fusion protein at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce one or more symptoms of PCIS relative to a control. 
     
     
         2 . A method of treating pericarditis, comprising a step of administering to a subject in need of treatment an interleukin-1 receptor-Fc fusion protein at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce one or more symptoms of pericarditis relative to a control. 
     
     
         3 . The method of  claim 2 , wherein the pericarditis is recurrent pericarditis. 
     
     
         4 - 26 . (canceled) 
     
     
         27 . The method of  claim 2 , wherein the subject is selected from any of the following:
 (i) a symptomatic subject with pericarditis with an elevated level of a marker of systemic inflammation;   (ii) a symptomatic subject with pericarditis with non-elevated levels of an inflammatory marker and with pericardial inflammation present using an imaging technique;   (iii) the subject of (i) or (ii), where the subject is NSAID-, corticosteroid- and/or colchicine-resistant or intolerant;   (iv) a subject with NSAID-, corticosteroid- and/or colchicine-dependent pericarditis not experiencing symptoms that would meet the diagnostic criteria for a flare of pericarditis;   (v) a symptomatic subject with PCIS with or without an elevated marker of systemic inflammation;   (vi) the subject of (v), where the subject is NSAID-, corticosteroid- and/or colchicine-resistant or intolerant; and/or   (vii) a subject with NSAID-, corticosteroid- and/or colchicine-dependent PCIS not experiencing symptoms that would meet the diagnostic criteria for PCIS, such as, for example, criteria for a flare of pericarditis.   
     
     
         28 - 37 . (canceled) 
     
     
         38 . The method of  claim 2 , wherein the therapeutically effective dose is equal to or greater than 320 mg. 
     
     
         39 - 65 . (canceled) 
     
     
         66 . The method of  claim 2 , wherein the one or more symptoms of pericarditis are assessed by a Numerical Rating Scale (NRS) for assessment of pericarditis pain. 
     
     
         67 . The method of  claim 2 , wherein the one or more symptoms of pericarditis are assessed by an echocardiogram. 
     
     
         68 - 71 . (canceled) 
     
     
         72 . The method of  claim 2 , wherein the one or more signs and symptoms of pericarditis are assessed by cardiac magnetic resonance imaging (MRI). 
     
     
         73 . The method of  claim 2 , wherein the one or more signs of pericarditis are assessed by measuring blood levels of C-reactive protein (CRP). 
     
     
         74 . (canceled) 
     
     
         75 . The method of  claim 2 , wherein the one or more symptoms of pericarditis are assessed by a Quality of Life Questionnaire. 
     
     
         76 . (canceled) 
     
     
         77 . The method of  claim 2 , wherein the control is indicative of the one or more symptoms of pericarditis in the subject before the treatment. 
     
     
         78 - 85 . (canceled) 
     
     
         86 . The method of  claim 2 , wherein the interleukin-1 receptor-Fc fusion protein comprises an amino acid sequence of SEQ ID NO: 1. 
     
     
         87 . (canceled) 
     
     
         88 . The method of  claim 2 , wherein the interleukin-1 receptor-Fc fusion protein comprises CH1 and CH2 domains derived from a human IgG1. 
     
     
         89 . The method of  claim 2 , wherein the interleukin-1 receptor-Fc fusion protein is rilonacept. 
     
     
         90 - 106 . (canceled) 
     
     
         107 . The method of  claim 2 , wherein administration of the interleukin-1 receptor-Fc fusion protein results in a reduced CRP level selected from less than about 2 mg/dL, less than about 1.5 mg/dL, less than about 1 mg/dL, less than about 0.8 mg/dL, less than about 0.6 mg/dL, less than about 0.5 mg/dL, less than about 0.4 mg/dL, less than about 0.3 mg/dL, less than about 0.2 mg/dL, or less than about 0.1 mg/dL in the subject. 
     
     
         108 - 137 . (canceled) 
     
     
         138 . The method of  claim 2 , wherein administration of the interleukin-1 receptor-Fc fusion protein results in a period of flare-free survival of the subject in absence of other standard of care (SOC) medicines. 
     
     
         139 . (canceled) 
     
     
         140 . A method of treating post-pericardiotomy syndrome (PPS), comprising a step of administering to a subject in need of treatment an interleukin-1 antagonist at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce one or more symptoms of post-pericardiotomy pericarditis relative to a control. 
     
     
         141 . The method of  claim 140 , wherein the interleukin-1 antagonist is a interleukin-1 binding protein or interleukin-1 receptor binding protein. 
     
     
         142 . The method of  claim 141 , wherein the binding protein is an antibody or a fragment thereof. 
     
     
         143 . The method of  claim 140 , wherein the interleukin-1 antagonist is a soluble receptor for interleukin-1 or interleukin-1 receptor antagonist (IL-1ra).