Theory, targets and therapy in systemic lupus erythematosus

The treatment of systemic lupus erythematosus (SLE) has been refined over the years, with the recognition that a fine balance lies between aggressive and prompt therapy and attendant complications brought upon by immunosuppressive therapy itself. However, there has been limited change to the repertoire of drugs available to treat this challenging disease. The current standard therapy for severe manifestations of SLE includes the use of high-dose corticosteroids and cytotoxic agents such as cyclophosphamide (CYC), which have been associated with an increased risk of serious and opportunistic infections. The need for safer, more targeted therapies has been recognized and now, with the exponential increase in the understanding of immunopathogenic mechanisms in SLE, the way has been paved for the development of biologic or targeted therapies in SLE. Although the potential immunosuppression, long-term safety issues and cost-effectiveness remain unclear. These targeted therapies may range from small molecules that specifically inhibit inflammatory processes at an intracellular, cell-cell or cell-matrix level to monoclonal antibodies, soluble receptors or natural antagonists that interfere with cytokine function, cellular activation and inflammatory gene transcription.