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

Japanese Eculizumab Trial for GBS (JET-GBS) Study Group

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)519-529
Number of pages11
JournalThe Lancet Neurology
Volume17
Issue number6
DOIs
Publication statusPublished - 2018 Jun 1

Fingerprint

Safety
Placebos
Anaphylaxis
Abscess
Japan
eculizumab
Complement C5
Outcome Assessment (Health Care)
Meningococcal Infections
Antibodies, Monoclonal, Humanized
Passive Immunization
Plasmapheresis
Intracranial Hemorrhages
Intravenous Immunoglobulins
Random Allocation
Peripheral Nerves
Biomedical Research
Complement System Proteins
Randomized Controlled Trials
Health

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Safety and efficacy of eculizumab in Guillain-Barré syndrome : a multicentre, double-blind, randomised phase 2 trial. / Japanese Eculizumab Trial for GBS (JET-GBS) Study Group.

In: The Lancet Neurology, Vol. 17, No. 6, 01.06.2018, p. 519-529.

Research output: Contribution to journalArticle

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. In: The Lancet Neurology. 2018 ; Vol. 17, No. 6. pp. 519-529.
@article{f841d871ebca4aa08d65db6ad889f838,
title = "Safety and efficacy of eculizumab in Guillain-Barr{\'e} syndrome: a multicentre, double-blind, randomised phase 2 trial",
abstract = "Background: Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barr{\'e} 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-Barr{\'e} 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-Barr{\'e} syndrome were aged 18 years or older and could not walk independently (Guillain-Barr{\'e} 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.",
author = "{Japanese Eculizumab Trial for GBS (JET-GBS) Study Group} and Sonoko Misawa and Satoshi Kuwabara and Yasunori Sato and Nobuko Yamaguchi and Kengo Nagashima and Kanako Katayama and Yukari Sekiguchi and Yuta Iwai and Hiroshi Amino and Tomoki Suichi and Takanori Yokota and Yoichiro Nishida and Tadashi Kanouchi and Nobuo Kohara and Michi Kawamoto and Junko Ishii and Motoi Kuwahara and Hidekazu Suzuki and Koichi Hirata and Norito Kokubun and Ray Masuda and Juntaro Kaneko and Ichiro Yabe and Hidenao Sasaki and Kaida, {Ken ichi} and Hiroshi Takazaki and Norihiro Suzuki and Shigeaki Suzuki and Hiroyuki Nodera and Naoko Matsui and Shoji Tsuji and Haruki Koike and Ryo Yamasaki and Susumu Kusunoki and S. Misawa and S. Kuwabara and Y. Sato and N. Yamaguchi and K. Nagashima and K. Katayama and Y. Sekiguchi and Y. Iwai and H. Amino and T. Suichi and T. Yokota and Y. Nishida and T. Kanouchi and N. Kohara and M. Kawamoto and Jin Nakahara",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/S1474-4422(18)30114-5",
language = "English",
volume = "17",
pages = "519--529",
journal = "The Lancet Neurology",
issn = "1474-4422",
publisher = "Lancet Publishing Group",
number = "6",

}

TY - JOUR

T1 - Safety and efficacy of eculizumab in Guillain-Barré syndrome

T2 - a multicentre, double-blind, randomised phase 2 trial

AU - Japanese Eculizumab Trial for GBS (JET-GBS) Study Group

AU - Misawa, Sonoko

AU - Kuwabara, Satoshi

AU - Sato, Yasunori

AU - Yamaguchi, Nobuko

AU - Nagashima, Kengo

AU - Katayama, Kanako

AU - Sekiguchi, Yukari

AU - Iwai, Yuta

AU - Amino, Hiroshi

AU - Suichi, Tomoki

AU - Yokota, Takanori

AU - Nishida, Yoichiro

AU - Kanouchi, Tadashi

AU - Kohara, Nobuo

AU - Kawamoto, Michi

AU - Ishii, Junko

AU - Kuwahara, Motoi

AU - Suzuki, Hidekazu

AU - Hirata, Koichi

AU - Kokubun, Norito

AU - Masuda, Ray

AU - Kaneko, Juntaro

AU - Yabe, Ichiro

AU - Sasaki, Hidenao

AU - Kaida, Ken ichi

AU - Takazaki, Hiroshi

AU - Suzuki, Norihiro

AU - Suzuki, Shigeaki

AU - Nodera, Hiroyuki

AU - Matsui, Naoko

AU - Tsuji, Shoji

AU - Koike, Haruki

AU - Yamasaki, Ryo

AU - Kusunoki, Susumu

AU - Misawa, S.

AU - Kuwabara, S.

AU - Sato, Y.

AU - Yamaguchi, N.

AU - Nagashima, K.

AU - Katayama, K.

AU - Sekiguchi, Y.

AU - Iwai, Y.

AU - Amino, H.

AU - Suichi, T.

AU - Yokota, T.

AU - Nishida, Y.

AU - Kanouchi, T.

AU - Kohara, N.

AU - Kawamoto, M.

AU - Nakahara, Jin

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85045902073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045902073&partnerID=8YFLogxK

U2 - 10.1016/S1474-4422(18)30114-5

DO - 10.1016/S1474-4422(18)30114-5

M3 - Article

C2 - 29685815

AN - SCOPUS:85045902073

VL - 17

SP - 519

EP - 529

JO - The Lancet Neurology

JF - The Lancet Neurology

SN - 1474-4422

IS - 6

ER -