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

Autor: R Yamasaki, K Kaida, Nobuo Kohara, T Nagashima, Ryo Yamasaki, S Suzuki, H Suzuki, I Yabe, S Kuwabara, M Kuwahara, T Shimizu, M Hirotani, Hiroshi Takazaki, M Tanaka, Shoji Tsuji, Ray Masuda, Yoichiro Nishida, Norito Kokubun, Hidenao Sasaki, Kengo Nagashima, T Yokota, Tomoki Suichi, J Kaneko, Motoi Kuwahara, Y Sato, Tadashi Kanouchi, N Yamaguchi, Masahisa Katsuno, H Yamaguchi, Junko Ishii, N Matsui, Jin Nakahara, Hiroshi Amino, Nobuko Yamaguchi, Kenichi Kaida, Ichiro Yabe, Naoko Matsui, J Shimizu, Michi Kawamoto, Y Sekiguchi, Norihiro Suzuki, T Kanouchi, K Katayama, Shigeaki Suzuki, R Masuda, N Suzuki, H Ogata, Yuta Iwai, G Sobue, S Tsuji, Y Nishida, H Amino, H Sasaki, S Kusunoki, H Koike, N Kokubun, Y Iwai, Satoshi Kuwabara, Takanori Yokota, M Kawamoto, T Suichi, J Ishii, Kanako Katayama, Yasunori Sato, Koichi Hirata, K Hirata, H Takazaki, S Misawa, N Kohara, Yukari Sekiguchi, Haruki Koike, Sonoko Misawa, K Nagashima, M Kadoya, Hiroyuki Nodera, Juntaro Kaneko, Hidekazu Suzuki, H Nodera, Susumu Kusunoki
Rok vydání: 2017
Předmět:
Zdroj: The Lancet. Neurology. 17(6)
ISSN: 1474-4465
Popis: Summary Background Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barre 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-Barre 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-Barre syndrome were aged 18 years or older and could not walk independently (Guillain-Barre 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.
Databáze: OpenAIRE
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