The last significant breakthrough in the treatment of systemic lupus erythematosus (SLE) was the use of cyclophosphamide and methylprednisolone in the treatment of lupus nephritis. Recent advances in immunology, oncology, and endocrinology have resulted in many potential therapies for SLE. These therapies include new immunosuppressants, biologic medications, tolerizing agents, immunoablation techniques, and hormonal medications. Each of these approaches will be discussed in this review. Some therapies are currently in use in clinical rheumatology practice (mycophenolate mofetil) and others are entering phase I trials (anti-BLyS monoclonal antibody). While some of these new therapies target specific inflammatory mechanisms in SLE (anti-CD40L monoclonal antibody), others work by nonspecific inhibition of the immune system (immunoablation).
Abbreviations:APCs antigen-presenting cells, BLyS B lymphocyte stimulator, dsDNA double-stranded deoxyribonucleic acid, HSCT hematopoetic stem cell transplantation, MMF mycophenolate mofetil, SLE systemic lupus erythematosus
Since clinical trials for SLE were initiated at the National Institutes of Health over 30 years ago, cyclophosphamide has remained the gold standard for the treatment of major organ involvement in SLE. Cyclophosphamide, along with the multiple other medications used to treat SLE, nonspecifically inhibits the inflammatory immune response and therefore is associated with many side effects. Improved understanding of the molecular basis involved in the pathogenesis of SLE and recent accomplishments in organ transplantation and oncology have sparked a new generation of potential SLE treatments with improved side effect profiles and/or more specific targeting of the immune system. This review will summarize the most recent promising treatments for SLE.