BACKGROUND: 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.
METHODS: 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 ClinicalTrials.gov, 
number, NCT02493725.
FINDINGS: 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.
INTERPRETATION: 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.
FUNDING: The Japan Agency for Medical Research and Development, Ministry of 
Health, Labor and Welfare, and Alexion Pharmaceuticals.