Combination of BLyS and/or APRIL inhibition and immunosuppressants for treatment of autoimmune disease

摘要

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.

主权项

1. A method of reducing immunoglobulin levels in a mammal comprising administering a BLyS antagonist and mycophenolate mofetil (MMF), wherein said B Lymphocyte Stimulator (BLyS) antagonist and said MMF are administered in an amount such that the combination of the MMF and the BlyS antagonist act at synergistically to reduce immunoglobulin levels 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.