Monoclonal antibodies and other biologic therapies

The treatment of systemic lupus erythematosus (SLE) presents a significant therapeutic challenge: multi-organ involvement and a variable disease cours e characterized by clinical exacerbations and remissions make it difficult to predict outcome. Few products have been specifically developed in this c linical indication and most accepted therapies have not been tested in rand omized controlled trials in SLE. A variety of biologic agents under investi gation as potential treatments for SLE are designed to interfere with speci fic immunologic responses, hopefully avoiding generalized immunosuppression . These include therapies to downregulate IL-10 and/or upregulate TGFb prod uction, Agents which interfere with T cell activation and T cell-B cell col laboration, such as CTLA4-Ig and anti-CD40 ligand monoclonal antibodies, ma y result in long term therapeutic benefit; alone or in combination, even fo llowing brief treatment courses. Products designed to decrease production o f anti-dsDNA antibodies or inhibit complement activation may prevent immune complex deposition and amerliorate organ-specific manifestations such as r enal disease. More aggressive interventions include gene therapy and stem c ell transplantation. As these agents enter clinical trials, efforts to deve lop international consensus regarding trial methodology and outcome measure s will be crucial to their successful development.