Method for treating a LFA-1-mediated disorder

Abstract

A method is provided for administering to a mammal suffering from, or at risk for, a LFA-1-mediated disorder an initial dosing of a therapeutically effective amount of LFA-1 antagonist, followed by a subsequent intermittent dosing of a therapeutically effective amount of LFA-1 antagonist that is less than 100%, calculated on a daily basis, of the initial dosing of antagonist.

What is claimed is:  
     
         1 . A method for treating a LFA-1-mediated disorder in a mammal comprising administering to the mammal an initial dosing of a therapeutically effective amount of an LFA-1 antagonist, followed by a subsequent intermittent dosing of a therapeutically effective amount of LFA-1 antagonist that is less than 100%, calculated on a daily basis, of the initial dosing of the antagonist.  
     
     
         2 . The method of  claim 1  wherein the subsequent dosing is less than about 50% of the initial dosing of the antagonist.  
     
     
         3 . The method of  claim 1  wherein the subsequent dosing is less than about 25% of the initial dosing of the antagonist.  
     
     
         4 . The method of  claim 1  wherein the subsequent dosing is less than about 10% of the initial dosing of the antagonist.  
     
     
         5 . The method of  claim 1  wherein the subsequent dosing is less than about 2% of the initial dosing of the antagonist.  
     
     
         6 . The method of  claim 1  wherein the disorder is rejection of or by a transplanted graft.  
     
     
         7 . The method of  claim 6  wherein the initial dosing takes place before, during, and after transplantation has occurred.  
     
     
         8 . The method of  claim 1  further comprising administering an effective amount of an immunosuppressive agent to the mammal.  
     
     
         9 . The method of  claim 6  further comprising administering an effective amount of cyclosporin A to the mammal.  
     
     
         10 . The method of  claim 1  wherein the mammal is a human.  
     
     
         11 . The method of  claim 10  wherein the disorder is rejection of a transplanted graft, and the donor of the graft and the recipient are matched for HLA class II antigens.  
     
     
         12 . The method of  claim 1  wherein the subsequent dosing is carried out for a longer time than the initial dosing.  
     
     
         13 . The method of  claim 6  wherein the initial dosing consists of daily administration and the subsequent dosing is a dose administered no more than about once a week.  
     
     
         14 . The method of  claim 13  wherein the initial dosing comprises daily administration of antagonist for at least one week after the graft implant and the subsequent dosing comprises administration of antagonist no more than once biweekly for at least about 5 weeks after the end of the initial dosing.  
     
     
         15 . The method of  claim 6  wherein the antagonist is an anti-CD11a or anti-CD18 antibody and initial dosing terminates from about 1 day to 4 weeks after transplantation has occurred and commences from about 1 week before transplantation occurs up to about simultaneously with the transplantation.  
     
     
         16 . The method of  claim 6  wherein the dosing is given by intravenous or subcutaneous injections.  
     
     
         17 . The method of  claim 1  wherein the antagonist is an anti-LFA-1 antibody or an anti-ICAM-1 antibody.  
     
     
         18 . The method of  claim 17  wherein the antibody is an anti-CD11a or anti-CD18 antibody.  
     
     
         19 . The method of  claim 17  wherein the antibody is an anti-CD11a antibody.  
     
     
         20 . A method for increasing tolerance of a transplanted graft by a mammalian host or of the host by a transplanted graft comprising administering to the host an initial dosing of a therapeutically effective amount of anti-LFA-1 antibody, followed by a subsequent dosing of a therapeutically effective amount of anti-LFA-1 antibody that is less than 100%, calculated on a daily basis, of the initial dosing of anti-LFA-1 antibody.