Treatment of LFA-1 Associated Disorders with Increasing Doses of LFA-1 Antagonist

Abstract

A method is provided for reducing the occurrence of fever, headache, nausea and/or vomiting associated with administration of a therapeutic compound to a mammal in need thereof, comprising administering to the mammal a first conditioning dose of a non-target cell depleting compound which binds to a cell surface receptor on a target mammalian cell; and administering a second therapeutic dose of the compound, wherein the second dose is higher than the first dose.

1 . A method for treating dermatitis, comprising 
 administering to a mammal in need thereof a first conditioning dose of an antibody or a receptor binding fragment thereof which binds CD11a; and    administering a second therapeutic dose of the antibody, wherein the second dose is higher than the first dose.    
   
   
       2 . The method of  claim 1  wherein the antibody is a humanized antibody.  
   
   
       3 . The method of  claim 1 , further comprising administering a third therapeutic dose, wherein the third dose is higher than or equal to the second dose.  
   
   
       4 . The method of  claim 1 , further comprising administering a fourth therapeutic dose, wherein the fourth dose is higher than or equal to the third dose.  
   
   
       5 . The method of  claim 1  or  claim 2 , wherein administration is intravenous or subcutaneous.  
   
   
       6 . The method of  claim 1  or  claim 2 , wherein administration is not more than once per week.  
   
   
       7 . The method of  claim 1  or  claim 2 , wherein the antibody or receptor binding fragment thereof is non-lymphocyte depleting.  
   
   
       8 . The method of  claim 7 , wherein the antibody or receptor binding fragment thereof is non-T-cell depleting.  
   
   
       9 . The method of  claim 1  or  claim 2 , wherein the first conditioning dose is 0.7 mg/kg and the second therapeutic dose is 1.0 mg/kg.  
   
   
       10 . The method of  claim 1  or  claim 2 , wherein the first conditioning dose is 0.7 mg/kg and the second therapeutic dose is 2.0 mg/kg.  
   
   
       11 . A method for treating graft versus host or host versus graft transplant rejection, comprising 
 administering to a mammal in need thereof a first conditioning dose of an antibody or a receptor binding fragment thereof which binds CD11a; and    administering a second therapeutic dose of the antibody, wherein the second dose is higher than the first dose.    
   
   
       12 . The method of  claim 11  wherein the antibody is a humanized antibody.  
   
   
       13 . The method of  claim 11 , further comprising administering a third therapeutic dose, wherein the third dose is higher than or equal to the second dose.  
   
   
       14 . The method of  claim 11 , further comprising administering a fourth therapeutic dose, wherein the fourth dose is higher than or equal to the third dose.  
   
   
       15 . The method of  claim 11  or  claim 12 , wherein administration is intravenous or subcutaneous.  
   
   
       16 . The method of  claim 11  or  claim 12 , wherein administration is not more than once per week.  
   
   
       17 . The method of  claim 11  or  claim 12 , wherein the antibody or receptor binding fragment thereof is non-lymphocyte depleting.  
   
   
       18 . The method of  claim 17 , wherein the antibody or receptor binding fragment thereof is non-T-cell depleting.  
   
   
       19 . The method of  claim 11  or  claim 12 , wherein the first conditioning dose is 0.7 mg/kg and the second therapeutic dose is 1.0 mg/kg.  
   
   
       20 . The method of  claim 11  or  claim 12 , wherein the first conditioning dose is 0.7 mg/kg and the second therapeutic dose is 2.0 mg/kg.