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Lancet Neurol. 2018 Jun;17(6):519-529. doi: 10.1016/S1474-4422(18)30114-5. Epub 2018 Apr 21.

Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial.

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Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan. Electronic address:
Department of Global Clinical Research, Graduate School of Medicine, Chiba University, Chiba, Japan.
Clinical Research Center, Chiba University Hospital, Chiba, Japan.
Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Neurology, Kobe City Medical Center General Hospital, Kobe, Japan.
Department of Neurology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Department of Neurology, Dokkyo Medical University, Tochigi, Japan.
Department of Neurology, Kitasato University, Sagamihara, Japan.
Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Department of Neurology, National Defense Medical College, Tokorozawa, Japan.
Department of Neurology, Keio University, Tokyo, Japan.
Department of Neurology, Tokushima University, Tokushima, Japan.
Department of Neurology, University of Tokyo Hospital, Tokyo, Japan.
Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.



Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome.


This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with, number, NCT02493725.


Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred.


The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials.


The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals.

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