Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade

Abstract

Immune responses against endogenous nuclear antigens are characteristic of systemic lupus erythematosus (SLE), a highly pleiomorphic disease predominantly affecting young women of reproductive age. Genome-wide association studies have confirmed the importance of genes associated with the immune response as well as genes involved in endothelial function and tissue response to injury. Immune complexes, autoantibodies, complement, cytokines, endothelial injury and a thrombophilic state associated with antiphospholipid antibodies are important for mediating tissue dysfunction. If not treated promptly, a significant proportion of patients-especially those with more aggressive disease-accumulate irreversible damage. During the past decade, novel combinations of immunosuppressive drugs and biologicals have been added to the therapeutic armamentarium. At the same time, the emphasis in the management of lupus has shifted from individual drugs to a strategy that aims at early, sustained remission tailored to disease manifestations and severity with the lowest possible toxicity. Infections and accelerated atherosclerosis (attributed to both traditional and non-traditional risk factors) and thrombosis-related clinical events (including arterial, venous and pregnancy loss) represent a major challenge in the management of the disease. To avoid fragmentation and optimise medical care, evidence and expert-based recommendations have been developed. For the future the authors predict a new taxonomy on the basis of mechanisms rather than clinical empiricism, leading to targeted therapy.