COMBINATION OF BLyS AND/OR APRIL INHIBITION AND IMMUNOSUPPRESSANTS FOR TREATMENT OF AUTOIMMUNE DISEASE

Abstract

The invention relates to novel combination therapies involving BLyS or BLyS/APRIL inhibition and immunosuppressants for the treatment of autoimmune diseases. One preferred method is where the BLyS and/or APRIL antagonist is a Fc-fusion protein which can be a TACI-Fc-fusion protein comprising the extracellular domain of TACI or a functional fragment thereof, a BAFF-R-Fc-fusion protein comprising the extracellular domain of BAFF-R or a functional fragment thereof, or a BCMA-Fc-fusion protein comprising the extracellular domain of BCMA or a functional fragment thereof. In the methods of the present invention some of the immunosuppressive drugs contemplated include cyclophosphamide (CYC), azathioprine (AZA), cyclosporine A (CSA), or mycophenolate mofetil (MMF), although any drug that suppresses the immune system may be suitable. The methods of the present invention reduce the levels of various immunoglobulins in patients in need of such reduction, such as those suffering from autoimmune diseases.

1 - 44 . (canceled) 
     
     
         45 . A composition comprising a therapeutically effective amount of a B Lymphocyte Stimulator (BLyS) antagonist and mycophenolate mofetil (MMF), said BLyS antagonist comprises the TACI-Fc protein set forth in SEQ ID NO: 23, wherein the modified tissue plasminogen activation signal sequence has been removed from the protein set forth in SEQ ID NO: 23. 
     
     
         46 . The composition of  claim 45 , wherein said BLyS antagonist and said MMF are present in an amount such that the combination of the MMF and the BlyS antagonist when administered to a mammal act synergistically to reduce immunoglobulin levels in the mammal. 
     
     
         47 . The composition of  claim 46 , wherein the immunoglobulin level that is reduced comprising IgM, IgG, or IgA. 
     
     
         48 . A kit comprising a first container comprising a therapeutically effective amount of a B Lymphocyte Stimulator (BLyS) antagonist and a second container comprising a therapeutically effective amount of mycophenolate mofetil (MMF), said BLyS antagonist comprises the TACI-Fc protein set forth in SEQ ID NO: 23, wherein the modified tissue plasminogen activation signal sequence has been removed from the protein set forth in SEQ ID NO: 23. 
     
     
         49 . The kit of  claim 48 , wherein said BLyS antagonist and said MMF are present in an amount such that the combination of the MMF and the BlyS antagonist when administered to a mammal act synergistically to reduce immunoglobulin levels in the mammal. 
     
     
         50 . The kit of  claim 49 , wherein the immunoglobulin level that is reduced comprises IgM, IgG, or IgA.