Methods for treating ulcerative colitis

Abstract

The present disclosure provides methods and treatment regimens for treating ulcerative colitis in a subject in need thereof. In particular, the methods described herein comprise treating a subject in need thereof with a treatment regimen comprising the administration of a pharmaceutical composition comprising live non-pathogenic fecal bacteria for at least 8 weeks and at least three times per week. In an aspect, the subject in need thereof exhibits a Mayo endoscopy score of 3 or lower. In some aspects, the subject in need thereof has no concomitant corticosteroid use during said method and has no corticosteroid use immediately prior to commencing said method.

1 . A method for treating ulcerative colitis (UC) in a subject in need thereof comprising treating said subject with a treatment regimen comprising the administration of a pharmaceutical composition comprising live non-pathogenic fecal bacteria for at least 4 weeks and at least twice per week, wherein said treatment regimen is capable of achieving a primary outcome rate of at least two fold higher relative to a primary outcome rate from placebo, wherein said primary outcome is defined as a steroid-free clinical remission and endoscopic remission or response at the end of said treatment regimen, wherein said clinical remission is defined as a total Mayo score of 2 or lower with all sub-scores of 1 or lower, wherein said endoscopic remission or response is defined as a reduction of at least 1 point from baseline in Mayo endoscopy score, wherein said subject has no concomitant corticosteroid use during said method and wherein said subject has no steroid use within at least one week prior to commencing said method. 
     
     
         2 . A method for treating ulcerative colitis (UC) in a subject in need thereof, wherein said subject has no steroid use within at least one week prior to commencing said method, said method comprising treating said subject with a treatment regimen comprising the administration of a pharmaceutical composition comprising live non-pathogenic fecal bacteria for at least 8 weeks and at least three times per week, wherein said treatment regimen is capable of achieving a primary outcome rate of at least two fold higher relative to a primary outcome rate from placebo, wherein said primary outcome is defined as a steroid-free clinical remission and endoscopic remission or response at the end of said treatment regimen, wherein said clinical remission is defined as a total Mayo score of 2 or lower with all sub-scores of 1 or lower, wherein said endoscopic remission or response is defined as a reduction of at least 1 point from baseline in Mayo endoscopy score. 
     
     
         3 . The method of  claim 2 , wherein said treatment regimen is capable of achieving a primary outcome rate of at least 25%. 
     
     
         4 . The method of  claim 2 , wherein said treatment regimen is capable of achieving a clinical remission sustaining rate of at least 40% at 8 weeks after the completion of said treatment regimen. 
     
     
         5 . The method of  claim 1 , wherein said treatment regimen is capable of achieving a steroid-free clinical remission rate of at least two fold higher relative to a steroid-free clinical remission rate from placebo, wherein said clinical remission is defined as a combined Mayo score of 1 or lower for rectal bleeding and stool frequency. 
     
     
         6 . The method of  claim 5 , wherein said treatment regimen is capable of achieving a steroid-free clinical remission rate of at least 40%. 
     
     
         7 . The method of  claim 1 , wherein said treatment regimen is capable of achieving a steroid-free clinical response rate of at least two fold higher relative to a steroid-free clinical response rate from placebo, wherein said clinical response is defined as a total Mayo score decrease of 3 or higher or a 50% or higher reduction from baseline in combined score for rectal bleeding and stool frequency. 
     
     
         8 . The method of  claim 7 , wherein said treatment regimen is capable of achieving a steroid-free clinical response rate of at least 50%. 
     
     
         9 . The method of  claim 1 , wherein said treatment regimen is capable of achieving an endoscopic response rate of at least two fold higher relative to an endoscopic response rate from placebo, wherein said endoscopic response is defined as a total UCEIS score decrease of 3 or higher or a 50% or higher reduction from baseline. 
     
     
         10 . The method of  claim 9 , wherein said treatment regimen is capable of achieving an endoscopic response rate of at least 30%. 
     
     
         11 . The method of  claim 1 , wherein said method further comprises determining said subject's baseline gut bacterial diversity. 
     
     
         12 . The method of  claim 1 , wherein said method further comprises determining the level of one or more bacteria selected from the group consisting of  Fusobacterium, Sutterella, Barnesiella, Parabacteroides, Clostridium  IV,  Ruminococcus, Blautia, Dorea, Ruminococcus 2, and  Clostridium  XVIII in said subject's gut. 
     
     
         13 . The method of  claim 1 , wherein said pharmaceutical composition comprises a fecal microbiota preparation. 
     
     
         14 . The method of  claim 1 , wherein said subject exhibits a Mayo score of at least 4 prior to said treating. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , wherein said treatment regimen comprises administering said pharmaceutical composition for at least 8 weeks and at least five times per week. 
     
     
         22 . The method of  claim 1 , wherein said treatment regimen is capable of achieving a primary outcome rate of at least 25%. 
     
     
         23 . The method of  claim 1 , wherein said treatment regimen is capable of achieving a clinical remission sustaining rate of at least 40% at 8 weeks after the completion of said treatment regimen. 
     
     
         24 . The method of  claim 2 , wherein said treatment regimen is capable of achieving a steroid-free clinical remission rate of at least two fold higher relative to a steroid-free clinical remission rate from placebo, wherein said clinical remission is defined as a combined Mayo score of 1 or lower for rectal bleeding and stool frequency. 
     
     
         25 . The method of  claim 24 , wherein said treatment regimen is capable of achieving a steroid-free clinical remission rate of at least 40%. 
     
     
         26 . The method of  claim 2 , wherein said treatment regimen is capable of achieving a steroid-free clinical response rate of at least two fold higher relative to a steroid-free clinical response rate from placebo, wherein said clinical response is defined as a total Mayo score decrease of 3 or higher or a 50% or higher reduction from baseline in combined score for rectal bleeding and stool frequency. 
     
     
         27 . The method of  claim 26 , wherein said treatment regimen is capable of achieving a steroid-free clinical response rate of at least 50%. 
     
     
         28 . The method of  claim 2 , wherein said treatment regimen is capable of achieving an endoscopic response rate of at least two fold higher relative to an endoscopic response rate from placebo, wherein said endoscopic response is defined as a total UCEIS score decrease of 3 or higher or a 50% or higher reduction from baseline. 
     
     
         29 . The method of  claim 28 , wherein said treatment regimen is capable of achieving an endoscopic response rate of at least 30%. 
     
     
         30 . The method of  claim 2 , wherein said method further comprises determining said subject's baseline gut bacterial diversity. 
     
     
         31 . The method of  claim 2 , wherein said method further comprises determining the level of one or more bacteria selected from the group consisting of  Fusobacterium, Sutterella, Barnesiella, Parabacteroides, Clostridium  IV,  Ruminococcus, Blautia, Dorea, Ruminococcus 2, and  Clostridium  XVIII in said subject's gut. 
     
     
         32 . The method of  claim 2 , wherein said pharmaceutical composition comprises a fecal microbiota preparation. 
     
     
         33 . The method of  claim 2 , wherein said subject exhibits a Mayo score of at least 4 prior to said treating. 
     
     
         34 . The method of  claim 2 , wherein said treatment regimen comprises administering said pharmaceutical composition for at least 8 weeks and at least five times per week. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 1 , wherein said fecal bacteria are derived from multiple donors. 
     
     
         38 . The method of  claim 37 , wherein said fecal bacteria comprise cultured bacteria. 
     
     
         39 . The method of  claim 37 , wherein said fecal bacteria comprise a synthetic bacterial mixture. 
     
     
         40 . The method of  claim 2 , wherein said fecal bacteria are derived from multiple donors. 
     
     
         41 . The method of  claim 40 , wherein said fecal bacteria comprise cultured bacteria. 
     
     
         42 . The method of  claim 40 , wherein said fecal bacteria comprise a synthetic bacterial mixture. 
     
     
         43 . The method of  claim 1 , wherein said fecal bacteria are not from a single donor. 
     
     
         44 . The method of  claim 2 , wherein said fecal bacteria are not from a single donor. 
     
     
         45 . The method of  claim 1 , wherein said pharmaceutical composition comprises higher microbial heterogeneity than a fecal microbe composition derived from a single donor. 
     
     
         46 . The method of  claim 2 , wherein said pharmaceutical composition comprises higher microbial heterogeneity than a fecal microbe composition derived from a single donor. 
     
     
         47 . A method for treating ulcerative colitis (UC) in a subject in need thereof comprising treating said subject with a treatment regimen comprising the administration of a pharmaceutical composition comprising live non-pathogenic fecal bacteria for at least 4 weeks and at least once per week, wherein said pharmaceutical composition comprises fecal bacteria from multiple donors. 
     
     
         48 . The method of  claim 47 , wherein said treatment regimen achieves a primary outcome rate of at least two fold higher relative to a primary outcome rate from placebo, wherein said primary outcome is defined as a steroid-free clinical remission and endoscopic remission or response at the end of said treatment regimen, wherein said clinical remission is defined as a total Mayo score of 2 or lower with all sub-scores of 1 or lower, wherein said endoscopic remission or response is defined as a reduction of at least 1 point from baseline in Mayo endoscopy score. 
     
     
         49 . The method of  claim 47 , wherein said treatment regimen comprises administering said pharmaceutical composition for at least 8 weeks and at least five times per week. 
     
     
         50 . The method of  claim 47 , wherein said fecal bacteria comprise a synthetic bacterial mixture. 
     
     
         51 . A method for treating ulcerative colitis (UC) in a subject in need thereof comprising treating said subject with a treatment regimen comprising the administration of a pharmaceutical composition comprising live non-pathogenic fecal bacteria for at least 4 weeks and at least once per week, wherein said pharmaceutical composition comprises higher microbial heterogeneity than a fecal microbe composition derived from a single donor. 
     
     
         52 . The method of  claim 51 , wherein said treatment regimen achieves a primary outcome rate of at least two fold higher relative to a primary outcome rate from placebo, wherein said primary outcome is defined as a steroid-free clinical remission and endoscopic remission or response at the end of said treatment regimen, wherein said clinical remission is defined as a total Mayo score of 2 or lower with all sub-scores of 1 or lower, wherein said endoscopic remission or response is defined as a reduction of at least 1 point from baseline in Mayo endoscopy score. 
     
     
         53 . The method of  claim 51 , wherein said treatment regimen comprises administering said pharmaceutical composition for at least 8 weeks and at least five times per week. 
     
     
         54 . The method of  claim 51 , wherein said fecal bacteria comprise a synthetic bacterial mixture. 
     
     
         55 . A method for treating ulcerative colitis (UC) in a subject in need thereof comprising treating said subject with a treatment regimen comprising the administration of a pharmaceutical composition comprising live non-pathogenic fecal bacteria for at least 4 weeks and at least twice per week, wherein said subject has no concomitant corticosteroid use during said method and wherein said subject has no steroid use within at least one week prior to commencing said method. 
     
     
         56 . The method of  claim 55 , wherein said treatment regimen achieves a primary outcome rate of at least two fold higher relative to a primary outcome rate from placebo, wherein said primary outcome is defined as a steroid-free clinical remission and endoscopic remission or response at the end of said treatment regimen, wherein said clinical remission is defined as a total Mayo score of 2 or lower with all sub-scores of 1 or lower, wherein said endoscopic remission or response is defined as a reduction of at least 1 point from baseline in Mayo endoscopy score. 
     
     
         57 . The method of  claim 55 , wherein said treatment regimen comprises administering said pharmaceutical composition for at least 8 weeks and at least five times per week. 
     
     
         58 . The method of  claim 55 , wherein said fecal bacteria are not from a single donor. 
     
     
         59 . The method of  claim 55 , wherein said pharmaceutical composition comprises a fecal microbiota preparation.