PREDICTING OUTCOME OF TREATMENT WITH AN ANTI-alpha4beta7 INTEGRIN ANTIBODY

Abstract

The invention provides methods for treating patients with anti-α4β7 antibody comprising predicting outcome of the antibody therapy. The invention relates to the identification of patients who can respond to therapy comprising an anti-a4β7 antibody.

1 . A method of treating a patient suffering from Inflammatory Bowel Disease (IBD), the method comprising the steps of:
 a) measuring the concentration of vedolizumab in a patient wherein the patient was administered an induction phase dosing regimen of vedolizumab at least two weeks prior,   b) selecting the patient whose measurement of vedolizumab in step a) indicates low clearance; and   c) administering vedolizumab to the selected patient, thereby treating IBD.   
     
     
         2 . The method of  claim 1 , wherein the concentration of vedolizumab is a serum concentration. 
     
     
         3 . The method of  claim 2 , wherein the serum concentration is a trough serum concentration. 
     
     
         4 . The method of  claim 3 , wherein the patient is selected if the serum concentration is at least 8 μg per ml. 
     
     
         5 . The method of  claim 1 , wherein the concentration measurement is used to calculate the rate of clearance. 
     
     
         6 . The method of  claim 5 , wherein the patient is selected if the rate of clearance is less than 0.25 L/day. 
     
     
         7 . A method of treating a patient suffering from Inflammatory Bowel Disease (IBD), the method comprising the steps of:
 a) administering two doses of vedolizumab to the patient suffering from IBD, wherein the second dose is administered about two weeks after the first dose is administered to the patient;   b) selecting the patient wherein the patient has a serum concentration of at least 8 μg per ml as measured at least two weeks after the second dose; and   c) administering vedolizumab to the selected patient, thereby treating the patient having IBD.   
     
     
         8 . The method of  claim 7 , wherein the serum concentration is measured
 about four weeks after the second dose.   
     
     
         9 . The method of  claim 3 , wherein the patient's serum concentration is selected from the group consisting of 12-25 μg per ml, 15-17 μg per ml, 17-25 μg per ml, 12-40 μg per ml, and 17-40 μg per ml. 
     
     
         10 . The method of  claim 2 , wherein the vedolizumab serum concentration is measured by a sandwich ELISA assay. 
     
     
         11 . The method of  claim 1 , wherein the patient has mucosal healing. 
     
     
         12 . The method of  claim 1 , further comprising measuring an endoscopic subscore, wherein vedolizumab is continued with an endoscopic subscore of less than 3. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 12 , wherein vedolizumab is continued with an endoscopic subscore of less than 2. 
     
     
         15 . The method of  claim 1 , further comprising measuring SES-CO, wherein vedolizumab is continued with a SES-CD score ≦6. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , further comprising measuring MaRIA, wherein vedolizumab is continued with a MaRIA score <12. 
     
     
         18 . (canceled) 
     
     
         19 . The method of  claim 1 , further comprising measuring the fecal calprotectin concentration. 
     
     
         20 . The method of  claim 19 , wherein vedolizumab is continued with a fecal calprotectin concentration of <1500 μgig. 
     
     
         21 . The method of  claim 19 , wherein vedolizumab is continued if the fecal calprotectin is reduced to <50% of the concentration before treatment. 
     
     
         22 - 35 . (canceled) 
     
     
         36 . A method for maintaining remission of inflammatory bowel disease in a patient, wherein the patient has received at least one dose of vedolizumab in the previous two months, the method comprising:
 a) obtaining a serum sample from the patient;   b) measuring the concentration of vedolizumab in the sample;   c) administering vedolizumab thereafter every eight weeks if the concentration is at least 8 μg per ml.   
     
     
         37 - 45 . (canceled) 
     
     
         46 . The method of  claim 6 , further comprising measuring anti-vedolizumab antibodies. 
     
     
         47 . The method of  claim 46 , wherein an anti-vedolizumab antibody titer of ≦125 further identifies the patient for continued treatment with vedolizumab. 
     
     
         48 . The method of  claim 1 , further comprising measuring albumin concentration. 
     
     
         49 . The method of  claim 48 , wherein an albumin concentration >3.2 g/dL further identifies the patient for continued treatment with vedolizumab. 
     
     
         50 - 59 . (canceled) 
     
     
         60 . A method for achieving corticosteroid-free remission of a patient having inflammatory bowel disease (IBD), wherein the patient was dependent on corticosteroids, the method comprising the steps of:
 a) selecting a human patient having IBD and having a low clearance of vedolizumab at a time point that is four weeks after a second dose of vedolizumab, wherein a first dose of vedolizumab was administered to the subject two weeks prior to the second dose of vedolizumab,   b) administering vedolizumab to the human patient having IBD, and   c) decreasing the amount of corticosteroid by a tapering regimen, until no corticosteroid is being administered; thereby achieving corticosteroid-free remission in the patient having IBD.