title: A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis.
abstract: BACKGROUND
  Complement activation at the neuromuscular junction is a primary cause of acetylcholine receptor loss and failure of neuromuscular transmission in myasthenia gravis (MG). Eculizumab, a humanized monoclonal antibody, blocks the formation of terminal complement complex by specifically preventing the enzymatic cleavage of complement 5 (C5).
  
  
  METHODS
  This study was a randomized, double-blind, placebo-controlled, crossover trial involving 14 patients with severe, refractory generalized MG (gMG).
  
  
  RESULTS
  Six of 7 patients treated with eculizumab for 16 weeks (86%) achieved the primary endpoint of a 3-point reduction in the quantitative myasthenia gravis (QMG) score. Examining both treatment periods, the overall change in mean QMG total score was significantly different between eculizumab and placebo (P = 0.0144). After assessing data obtained from all visits, the overall change in mean QMG total score from baseline was found to be significantly different between eculizumab and placebo (P < 0.0001). Eculizumab was well tolerated.
  
  
  CONCLUSIONS
  The data suggest that eculizumab may have a role in treating severe, refractory MG.
authors.affiliation: Department of Neurology, University of North Carolina, 2200 Physicians Office Building, CB 7025, 170 Manning Drive, Chapel Hill, North Carolina, 27599-7025, USA. howardj@neurology.unc.edu
authors.forename: James F
authors.initials: JF
authors.lastname: Howard
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Barohn
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.forename: Miriam
authors.initials: M
authors.lastname: Freimer
authors.forename: Vern C
authors.initials: VC
authors.lastname: Juel
authors.forename: Tahseen
authors.initials: T
authors.lastname: Mozaffar
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Mellion
authors.forename: Michael G
authors.initials: MG
authors.lastname: Benatar
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Farrugia
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Wang
authors.forename: Suneil S
authors.initials: SS
authors.lastname: Malhotra
authors.forename: John T
authors.initials: JT
authors.lastname: Kissel
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D010865:Pilot Projects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab