title: Profile of atacicept and its potential in the treatment of systemic lupus erythematosus.
abstract: The importance of B cell activating factors in the generation of autoantibodies in patients with systemic lupus erythematosus (SLE) is now recognized. The two key factors, known as BAFF and APRIL, produced by a variety of cells including monocytes, dendritic cells and T cells, also help to regulate B cell maturation, function and survival. Biologic agents that block these factors have now been developed and tried out in large scale clinical trials in SLE patients. Benlysta which blocks BAFF has met some of its end points in clinical trials and is approved for use in patients with skin and joint disease who have failed conventional drugs. In contrast, clinical trials using atacicept which blocks both BAFF and APRIL have been more challenging to interpret. An early study in lupus nephritis was, mistakenly, abandoned due to serious infections thought to be linked to the biologic when in fact the dramatic fall in the immunoglobulin levels took place when the patients were given mycophenolate, prior to the introduction of the atacicept. Likewise the higher dose arm (150 mgm) of a flare prevention study was terminated prematurely when 2 deaths occurred. However, the mortality rate in this study was identical to that seen in the Benlysta studies and a post hoc analysis found a highly significant benefit for the 150mgm arm compared to the lower dose (75 mgm) and placebo arms. Other trials with both Benlysta and atacicept are on-going.
authors.forename: Estefania
authors.initials: E
authors.lastname: Cogollo
authors.affiliation: Department of Internal Medicine, Hospital Principe de Asturias, Alcala de Henares, Madrid, Spain.
authors.forename: Estafania
authors.initials: E
authors.lastname: Cogollo
authors.affiliation: Department of Internal Medicine, Hospital Distrital da Figueira da Foz, Coimbra, Portugal.
authors.forename: Marta Amaral
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Centre for Rheumatology, Department of Medicine, University College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Isenberg
mesh_terms: D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000037:antagonists & inhibitors
chemical_list: D053264:B-Cell Activating Factor; D011993:Recombinant Fusion Proteins; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C524618:TACI receptor-IgG Fc fragment fusion protein
keywords: APRIL; BLyS; cytokines; lupus nephritis
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