Methods for predicting response to treatment

Abstract

The present invention provides stratification methods and kits to identify whether an individual having an inflammation-related disorder has genotype-specific differential expression of IL-1, i.e., is a “high” or “low” producer of IL-1, such that s/he can be provided an appropriate anti-inflammatory drug and at an appropriate dose. The stratification of high or low IL-1 producers is used to guide assignment of different drug doses and therefore reduce drug toxicity and adverse events in an individual who, without stratification, may be prescribed a higher dose than needed to manage the primary indication. The use of IL-1 stratification of drug dosing would allow a better clinical benefit-risk appraisal in an individual patient.

1 - 110 . (canceled) 
     
     
         111 . A method of reducing the risk of an inflammation-related disorder associated with infection in a human subject, comprising steps of:
 (a) selecting a human subject with a diagnosis of, or suspected of having the infection;   (b) obtaining an isolated nucleic acid from a biological sample from the human subject;   (c) detecting the single nucleotide polymorphism (SNP) alleles in the isolated nucleic acid for each of the IL1B (−511) rs16944 C>T polymorphic locus, the IL1B (−1464) rs1143623 G>C polymorphic locus, the IL1B (−3737) rs4848306 C>T polymorphic locus, the ILIA (+4845) rs17561G>T polymorphic locus and the IL1B (+3954) rs1143634 C>T polymorphic locus;   (d) determining that the human subject has a positive IL-1 genotype pattern when the IL-1 genotype pattern obtained in (c) matches an IL-1 genotype pattern that is selected from the group consisting of:   (i) CC at rs16944, GG at rs1143623 and CT at rs4848306 and any allele at the rs17561 and rs1143634 loci,   (ii) CT at rs16944, GC at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,   (iii) CC at rs16944, GG at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,   (iv) CT at rs16944, GG at rs1143623 and CC at rs4848306 and any allele at the rs17561 and rs1143634 loci,   (v) CC at rs16944, GG at rs1143623 and TT at rs4848306 and any allele at the rs17561 and rs1143634 loci,   (vi) CT at rs16944, GC at rs1143623, CT at rs4848306, TT or TG at rs17561 and TT or TC at rs1143634,   (vii) CT at rs16944, GG at rs1143623, CT at rs4848306, TT or TG at rs17561 and TT or TC at rs1143634,   (viii) TT at rs16944, CC at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634,   (ix) TT at rs16944, CG at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634, and   (x) TT at rs16944, GG at rs1143623, CC at rs4848306, TT or TG at rs17561, and TT or TC at rs1143634;   (e) diagnosing the human subject as at risk of developing the inflammation-related disorder when the human subject has a positive IL-1 genotype pattern determined in step (d); and   (f) administering an anti-inflammatory drug to the human subject diagnosed in step (e).   
     
     
         112 . The method of  claim 111 , wherein the anti-inflammatory drug comprises an IL-1 inhibitor. 
     
     
         113 . The method of  112 , wherein the IL-1 inhibitor comprises a drug that binds directly to IL-1α or IL-1β to block binding to the IL-1 Receptor, an IL-1 Receptor Antagonist or an inflammasome modulator. 
     
     
         114 . The method of  claim 113 , wherein the inflammasome modulator is selected from the group consisting of Opsona, RON-2315, Diacerein, AC-701, Sairei-To, binimetinib, Can-04, Rilonacept, Tadekinig-alpha, XL-130, Givinostat and Ammonium trichlorotellurate. 
     
     
         115 . The method of  claim 113 , wherein the inflammasome modulator is a small molecule. 
     
     
         116 . The method of  claim 115 , wherein the small molecule is selected from the group consisting of Givinostat, Diacerein, Ammonium trichlorotellurate and binimetinib. 
     
     
         117 . The method of  claim 111 , wherein the IL-1 inhibitor is an IL-1β inhibitor. 
     
     
         118 . The method of  claim 111 , wherein the IL-1β inhibitor is Gevokizumab, Canakinumab, ABT-981, DLX-2681, APX-002, or Isunakinra.