Methods of Using IL-1 Antagonists to Treat Autoinflammatory Disease

Abstract

Methods of treating, inhibiting, or ameliorating an autoinflammatory disorder, disease, or condition in a subject in need thereof, comprising administering to a subject in need a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the autoinflammatory disorder, disease, or condition is treated, inhibited, or ameliorated. The IL-1 antagonist is an IL-1 trap, preferably comprising a sequence selected from the group consisting of SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, or a substantially identical having at least 95% identity to the sequence shown in SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and capable of binding and inhibiting IL-1. The therapeutic methods are useful for treating a human adult or child suffering from Neonatal Onset Multisystem Inflammatory Disorder (NOMID/CINCA), Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory Syndrome (FCAS), familial mediterranean fever (FMF), or systemic onset juvenile rheumatoid arthritis (Still's Disease).

1 . A method of treating, inhibiting, or ameliorating an autoinflammatory disorder, disease, or condition in a subject in need thereof, comprising administering to the subject a therapeutic amount of an interleukin 1 (IL-1) fusion protein antagonist once a week, wherein the autoinflammatory disorder, disease, or condition is treated, inhibited, or ameliorated, wherein the IL-1 fusion protein antagonist comprises two IL-1 receptor components and a multimerizing component, wherein the fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:10, wherein the subject is a human adult or child diagnosed with Neonatal Onset Multisystem Inflammatory Disorder (NOMID/CINCA), Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory Syndrome (FCAS), familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), or systemic onset juvenile idiopathic arthritis (Still's Disease). 
     
     
         2 . The method of  claim 1 , wherein the fusion protein comprises a sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:10. 
     
     
         3 . The method of  claim 1 , wherein administration is subcutaneous, intramuscular, or intravenous. 
     
     
         4 . The method of  claim 1 , wherein the therapeutically effective amount is between 1-20 mg/kg. 
     
     
         5 . A method of treating, inhibiting, or ameliorating an autoinflammatory disorder associated with mutations in CIAS-1 in a subject in need thereof, comprising administering once a week to the subject a therapeutic amount of an interleukin 1 (IL-1) antagonist, wherein the IL-1 antagonist comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:10, wherein the autoinflammatory disorder is treated, inhibited, or ameliorated, and wherein the autoinflammatory disorder associated with mutations in CIAS-1 is one of Neonatal Onset Multisystem Inflammatory Disorder (NOMID/CINCA), Muckle-Wells Syndrome (MWS), and Familial Cold Autoinflammatory Syndrome (FCAS). 
     
     
         6 . The method according to  claim 5 , wherein the IL-1 antagonist comprises an amino acid sequence that is at least 97% identical to the amino acid sequence of SEQ ID NO:10. 
     
     
         7 . The method of  claim 5 , wherein administration is subcutaneous, intramuscular, or intravenous. 
     
     
         8 . The method of  claim 5 , wherein the therapeutically effective amount is between 1-20 mg/kg.