Vedolizumab for the Treatment of Fistulizing Crohn's Disease

Abstract

A method for treating a human patient suffering from fistulizing Crohn's disease, comprising administering to a patient suffering from fistulizing Crohn's disease, a humanized antibody having binding specificity for human α4β7 integrin, wherein the human patient has a seton that was surgically placed prior to administration of the antibody, and wherein the dosing regimen induces fistula(e) healing.

1 . A method for treating a human patient suffering from fistulizing Crohn's disease, wherein the method comprises the step of:
 administering to a patient suffering from fistulizing Crohn's disease, a humanized antibody having binding specificity for human α4β7 integrin,   wherein the humanized antibody is administered to the patient according to the following dosing regimen:
 a. an initial dose of 300 mg of the humanized antibody as an intravenous infusion; 
 b. followed by a second subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about two weeks after the initial dose; 
 c. followed by a third subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about six weeks after the initial dose; 
 d. followed by a fourth subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about ten weeks after the initial dose; 
 e. followed by a fifth subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about 14 weeks after the initial dose; 
 f. followed by a sixth and subsequent doses of 300 mg of the humanized antibody as an intravenous infusion every eight weeks after the fifth subsequent dose of the humanized antibody as needed; 
   wherein the human patient has a seton that was surgically placed prior to administration of the antibody   wherein the dosing regimen induces fistula(e) healing; and   further wherein the humanized antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized antibody has binding specificity for the α4β7 complex, wherein the antigen-binding region comprises the CDRs:   Light chain: CDR1 SEQ ID NO:7
 CDR2 SEQ ID NO:8 and 
 CDR3 SEQ ID NO:9; and 
   Heavy chain: CDR1 SEQ ID NO:4
 CDR2 SEQ ID NO:5 and 
 CDR3 SEQ ID NO:6. 
   
     
     
         2 . The method of  claim 1 , wherein said fistula is one or more draining fistula. 
     
     
         3 . The method of  claim 1 , wherein said fistula(e) is one or more perianal fistula(e). 
     
     
         4 . The method of  claim 1 , wherein fistula(e) healing is measured by magnetic resonance imaging (MRI) assessment of fistula(e) healing at week 30. 
     
     
         5 . The method of  claim 2 , wherein at least 50% of draining fistulae are closed. 
     
     
         6 . The method of  claim 5 , wherein the at least 50% of draining fistulae are closed by 14 weeks after the initial dose of the humanized antibody. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the patient had a lack of an adequate response with, loss response to, or was intolerant to treatment with at least one of an immunomodulator, a tumor necrosis factor-alpha antagonist or combinations thereof. 
     
     
         9 . The method of  claim 1 , wherein the Crohn's disease is moderately to severely active Crohn's disease. 
     
     
         10 - 13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the patient had a lack of an adequate response with or loss of response to a corticosteroid. 
     
     
         15 . The method of  claim 8 , wherein the immunomodulator is azathioprine, 6-mercaptopurine, or methotrexate. 
     
     
         16 . The method of  claim 1 , wherein said treatment is measured by a PDAI score or a CDAI score of the patient. 
     
     
         17 . The method according to  claim 16 , wherein said PDAI score of the patient is reduced by at least 3 points from baseline. 
     
     
         18 . The method of  claim 1 , wherein the humanized antibody has a heavy chain variable region sequence of amino acids 20 to 140 of SEQ ID NO:1. 
     
     
         19 . The method of  claim 1 , wherein the humanized antibody has a light chain variable region sequence of amino acids 20 to 131 of SEQ ID NO:2. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . A method for treating a human patient suffering from fistulizing Crohn's disease, wherein the method comprises the step of:
 administering to a patient suffering from fistulizing Crohn's disease, a humanized antibody having binding specificity for human α4β7 integrin,   wherein the humanized antibody is administered to the patient according to the following dosing regimen:
 a. an initial dose of 300 mg of the humanized antibody as an intravenous infusion; 
 b. followed by a second subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about two weeks after the initial dose; 
 c. followed by a third subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about six weeks after the initial dose; 
 d. followed by a fourth subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about 14 weeks after the initial dose; 
 e. followed by a fifth subsequent dose and additional subsequent doses of 300 mg of the humanized antibody as an intravenous infusion every eight weeks after the fourth subsequent dose of the humanized antibody as needed; 
   wherein the human patient has a seton that was surgically placed prior to administration of the antibody   wherein the dosing regimen induces fistula(e) healing; and   further wherein the humanized antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized antibody has binding specificity for the α4β7 complex, wherein the antigen-binding region comprises the CDRs:   Light chain: CDR1 SEQ ID NO:7
 CDR2 SEQ ID NO:8 and 
 CDR3 SEQ ID NO:9; and 
   Heavy chain: CDR1 SEQ ID NO:4
 CDR2 SEQ ID NO:5 and 
 CDR3 SEQ ID NO:6. 
   
     
     
         23 . The method of  claim 22 , wherein said fistula(e) is one or more draining fistula. 
     
     
         24 . The method of  claim 22 , wherein said fistula(e) is one or more perianal fistula. 
     
     
         25 . The method of  claim 22 , wherein fistula(e) healing is measured by magnetic resonance imaging (MRI) assessment of fistula(e) healing at week 30. 
     
     
         26 . The method of  claim 23 , wherein at least 50% of draining fistulae are closed. 
     
     
         27 . The method of  claim 26 , wherein the at least 50% of draining fistulae are closed by 14 weeks after the initial dose of the humanized antibody. 
     
     
         28 - 42 . (canceled)