The use of eculizumab in patients with Guillain-Barré syndrome is safe and potentially associated with improvements in motor function, according to a randomized phase 2 trial published in Lancet Neurology.
Adult patients with Guillain-Barré syndrome were randomly assigned 2:1 to receive intravenous immunoglobulin plus either 900 mg eculizumab (n=23) or placebo (n=11) for 4 weeks. Safety in the both groups as well as the proportion of patients in the eculizumab group regaining their independent walking ability (functional grade ≤2) by 4 weeks comprised the primary outcome. Functional grade scores were categorized as healthy (0), minor symptoms or signs and able to run (1), able to walk 5 meters independently (2), able to walk 5 meters with a walker or with support (3), bed bound or chair bound (4), requires assisted respiration (5), or dead (6). A response rate threshold of the lower 90% CI boundary exceeding 50% defined the efficacy portion of the primary outcome. All outcomes were assessed at baseline and up to 24 weeks.
Approximately 61% of patients in the eculizumab group reached the efficacy end point at week 4 (90% CI, 42-78; n=14) compared with 45% of patients in the placebo group reaching the same end point (90% CI, 20-73; n=5). Using the generalized linear mixed model for the sensitivity analysis, the percentage of patients who met the primary efficacy outcome of 4-week functional grade ≤2 was 65% (95% CI, 37-85) and 45% (95% CI, 16-79) (P =.325) in the eculizumab and placebo groups, respectively.
At 24 weeks, approximately 92% of patients in eculizumab group (95% CI, 67-98) and 72% in the placebo group (95% CI, 32-93) achieved the primary efficacy outcome. All patients experienced adverse events during the study period, including insomnia, headache, constipation, rash, nausea, and oral mucositis. Serious adverse events occurred in 2 patients taking eculizumab (anaphylaxis [n=1] and intracranial hemorrhage and abscess [n=1]) and in 1 patient in the placebo group (depression).
High-dose intravenous immunoglobulin therapy was administered to all patients and may have contributed to neutralization of eculizumab. Additionally, the small number of patients in this study may further limit the findings.
The investigators concluded “that terminal complement inhibition with eculizumab might have the potential to suppress complement-mediated nerve damage and safely facilitate clinical recovery in patients with severe Guillain-Barré syndrome.”
Misawa S, Kuwabara S, Sato Y, et al; for the Japanese Eculizumab Trial for GBS (JET-GBS) Study Group. Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial [published online April 20, 2018]. Lancet Neurol. doi: 10.1016/S1474-4422(18)30114-5