title: Why targeted therapies are necessary for systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side effects. Current management strategies rely heavily on nonspecific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic preclinical data and promising early phase studies have ultimately been disappointing in phase III, randomized, controlled studies. Recent efforts have focused on B-cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated, including interferon-alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective.
authors: Division of Rheumatology, University of Washington, Seattle, WA, USA.
authors: L
authors: L
authors: Durcan
authors: Division of Rheumatology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA mpetri@jhmi.edu.
authors: M
authors: M
authors: Petri
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016898:Interferon-alpha / Q000037:antagonists & inhibitors; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods; D057285:Precision Medicine; D016032:Randomized Controlled Trials as Topic
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; C511911:belimumab
keywords: SLE; current treatments; mechanisms of disease; targeted therapy; treatment