title: Inhibition of complement in Guillain-Barré syndrome: the ICA-GBS study.
abstract: The outcome of Guillain-Barré syndrome (GBS) remains unchanged since plasma exchange and intravenous immunoglobulin (IVIg) were introduced over 20 years ago. Pathogenesis studies on GBS have identified the terminal component of complement cascade as a key disease mediator and therapeutic target. We report the first use of terminal complement pathway inhibition with eculizumab in humans with GBS. In a randomised, double-blind, placebo-controlled trial, 28 subjects eligible on the basis of GBS disability grade of at least 3 were screened, of whom 8 (29%) were randomised. Five received eculizumab for 4 weeks, alongside standard IVIg treatment. The safety outcomes, monitored via adverse events capture, showed eculizumab to be well-tolerated and safe when administered in conjunction with IVIg. Primary and secondary efficacy outcomes in the form of GBS disability scores (GBS DS), MRC sum scores, Rasch overall disability scores, and overall neuropathy limitation scores are reported descriptively. For the primary efficacy outcome at 4 weeks after recruitment, two of two placebo- and two of five eculizumab-treated subjects had improved by one or more grades on the GBS DS. Although the small sample size precludes a statistically meaningful analysis, these pilot data indicate further studies on complement inhibition in GBS are warranted.
authors: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.|Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, Scotland.
authors: Amy I
authors: AI
authors: Davidson
authors: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors: Susan K
authors: SK
authors: Halstead
authors: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.|Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, Scotland.
authors: John A
authors: JA
authors: Goodfellow
authors: Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, Scotland.
authors: Govind
authors: G
authors: Chavada
authors: Department of Clinical Neurophysiology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, Scotland.
authors: Arup
authors: A
authors: Mallik
authors: Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, Scotland.
authors: James
authors: J
authors: Overell
authors: Department of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.
authors: Michael P
authors: MP
authors: Lunn
authors: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, Scotland.
authors: Alex
authors: A
authors: McConnachie
authors: Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.
authors: Pieter
authors: P
authors: van Doorn
authors: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.|Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, Scotland.
authors: Hugh J
authors: HJ
authors: Willison
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D020143:Gangliosidoses, GM2 / Q000378:metabolism; D016537:Gangliosidosis, GM1 / Q000378:metabolism; D020275:Guillain-Barre Syndrome / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; C481642:eculizumab
keywords: Guillain-Barré syndrome; clinical trial; complement; eculizumab; intravenous immunoglobulin; membrane attack complex; therapy