title: The role of biological agents in the management of large vessel vasculitis (LVV): a systematic review and meta-analysis.
abstract: BACKGROUND
  Giant cell arteritis (GCA) and Takayasu's arteritis (TAA) are large vessel vasculitides (LVV) for which corticosteroids (CS) are the mainstay for treatment. In patients with LVV unable to tolerate CS, biological agents have been used with variable effectiveness.
  
  
  OBJECTIVE
  To systematically review the effectiveness and safety of biological agents in patients with LVV.
  
  
  METHODS
  We searched 5 electronic databases (inception to October 2012) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. Our protocol was registered in PROSPERO.
  
  
  RESULTS
  We included 25 studies (3 RCTs and 22 case series with ≥2 cases). 95 GCA and 98 TAA patients received biological agents. The RCTs using anti-TNF agents (infliximab, etanercept and adalimumab) did not suggest a benefit in GCA. GCA patients receiving tocilizumab, in case series, achieved remission (19 patients) and reduction of corticosteroid dose (mean difference, -16.55 mg/day (95% CI: -26.24, -6.86)). In case series, 75 patients with refractory TAA treated with infliximab discontinued CS 32% of the time. Remission was variably defined and the studies were clinically heterogeneous which precluded further analysis.
  
  
  CONCLUSIONS
  This systematic review demonstrated a weak evidence base on which to assess the effectiveness of biological treatment in LVV. Evidence from RCTs suggests that anti-TNF agents are not effective for remission or reduction of CS use. Tocilizumab and infliximab may be effective in the management of LVV and refractory TAA, respectively, although the evidence comes from case series. Future analytical studies are needed to confirm these findings.
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Osman
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Pagnoux
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Dryden
authors.affiliation: University of Alberta Health Sciences Library, Edmonton, Alberta, Canada.
authors.forename: Dale
authors.initials: D
authors.lastname: Storie
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: Yacyshyn
mesh_terms: D001685:Biological Factors / Q000009:adverse effects / Q000627:therapeutic use*; D013700:Giant Cell Arteritis / Q000188:drug therapy*; D006801:Humans; D013625:Takayasu Arteritis / Q000188:drug therapy*
chemical_list: D001685:Biological Factors