title: Safety of off-label biologicals in systemic lupus erythematosus.
abstract: BACKGROUND
  The approval of belimumab and other advances in the field have narrowed the window for off-label use of biologicals in systemic lupus erythematosus (SLE). For consideration in severe and refractory disease, safety will play a major role.
  
  
  METHODS
  We reviewed the literature on safety aspects of off-label biological use in SLE. Significant evidence is available for rituximab, whereas data on the off-label SLE therapy with other biologicals are much more limited. Published trials and open-label experience in SLE allow for some conclusions on abatacept, and on approaches targeting TNF, IL-1 and IL-6 receptors.
  
  
  CONCLUSIONS
  Anti-TNF antibodies apparently are the only ones inducing SLE-specific autoantibodies, but even these were not associated with flares. Risks for severe infections certainly remain a major serious concern, particularly in combinations with glucocorticoids and/or immunosuppressants. These findings reiterate that experience with both the disease and the drugs will be essential for keeping patients safe. The available data suggest a manageable adverse event profile for rituximab and do not prove unacceptable risks for other biologicals. Reports frequently only include very few patients, with the inherent danger of bias due to lacking reports on failed treatment attempts.
authors.affiliation: University Medical Center and Faculty of Medicine at the TU Dresden, Division of Rheumatology, Department of Medicine III , Dresden , Germany Martin.Aringer@uniklinikum-dresden.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Aringer
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects; D001688:Biological Products / Q000009:adverse effects*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D056687:Off-Label Use; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D001688:Biological Products; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: abatacept; adverse events; etanercept; infections; infliximab; malignancy; progressive multifocal leukoencephalopathy; rituximab; sle; tocilizumab