Treatment of LFA-1 associated disorders with increasing doses

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 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.    
     
     
         2 . The method of  claim 1 , wherein the therapeutic compound comprises a polypeptide which binds to an extracellular domain of the receptor molecule.  
     
     
         3 . The method of  claim 2 , wherein the polypeptide is an antibody or a receptor binding fragment thereof.  
     
     
         4 . The method of  claim 1 , wherein the target mammalian cell is a lymphocyte.  
     
     
         5 . The method of  claim 4 , wherein the lymphocyte is a T-cell.  
     
     
         6 . The method of  claim 5 , wherein the cell surface receptor on the T cell is CD11a or CD18.  
     
     
         7 . The method of  claim 6 , wherein the cell surface receptor is CD11a and the antibody is antibody hu1124.  
     
     
         8 . The method of  claim 7 , wherein the antibody or a receptor binding fragment thereof is non-lymphocyte depleting.  
     
     
         9 . The method of  claim 7 , wherein the antibody is a humanized antibody.  
     
     
         10 . The method of  claim 1 , further comprising administering a third therapeutic dose, wherein the third dose is higher than the second dose.  
     
     
         11 . The method of  claim 10 , further comprising administering a fourth therapeutic dose, wherein the fourth dose is higher than the third dose.  
     
     
         12 . The method of  claim 1 , wherein administration is intravenous or subcutaneous.  
     
     
         13 . The method of  claim 1 , wherein administration is not more than once per week.  
     
     
         14 . The method of  claim 7 , wherein the antibody is administered for the treatment of psoriasis, asthma, or transplant rejection.  
     
     
         15 . The method of  claim 7 , wherein the antibody is administered for the treatment of rheumatoid arthritis, systemic lupus erythmatosus or multiple sclerosis.