Submitted by Leigh Maria K. Ramos-Platt, MD, News Science Editorial Board
Edited by Benn E. Smith, MD, News Science Editorial Board
Misawa, S. et al. Safety and efficacy of eculizumab in Guillain-Barré syndrome: A multicentre, double-blind, randomised phase 2 trial
. The Lancet Neurology
. Volume 17, Issue 6, 519-529.
Eculizumab is an anti-C5 humanized monoclonal antibody. Misawa et al report on a 34 patient, 24-week double-blind, randomized phase 2 study comparing IVIG and 4 weeks of eculizumab (900 mg per dose) versus IVIG and 4 weeks of placebo. The study took place in 13 hospitals in Japan between August 10, 2015, and April 21, 2016.
The dose of a single course of IVIG was 400 mg/kg/day x 5 days. The first dose of eculizumab was given before the course of steroids. Patients were randomized in a 2:1 nature (23 patients received eculizumab and 11 patients received placebo).
The reason for the study was the observation that there is a significant proportion of patients with Guillain-Barré syndrome (GBS) who have significant chronic impairment after treatment. There have been studies demonstrating the role of the complement system in GBS. The efficacy endpoint was proportion of patients that could walk 5 meters independently by week 4. Safety was a second measure. In the treatment group, at 4 weeks, 61% were able to ambulate independently (90% CI 42-78) vs 45% in the placebo group (CI 20-73). One patient in the eculizumab group had an anaphylactic reaction and a second had a brain hemorrhage with subsequent development of an abscess in the area of hemorrhage. One patient in the placebo group developed depression. The authors concluded that because of the lower bound of the CI in the treatment group, the primary outcome measure did not reach the predefined response rate and suggested the need for a larger study.
Monoclonal antibodies against the complement system have demonstrated to be helpful in other autoimmune disorders. One of these disorders is a neuromuscular disorder, refractory myasthenia gravis. The authors have a valid point that the above study is relatively small. In comparison, the REGAIN study evaluating the effectiveness of eculizumab for refractory myasthenia gravis had 4 times as many patients.