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

Amino, Hiroshi; Suichi, Tomoki; Kanouchi, Tadashi; Hirata, Koichi; Kokubun, Norito; Yabe, Ichiro; Takazaki, Hiroshi; Suzuki, Norihiro; Nodera, Hiroyuki; Tsuji, Shoji; Koike, Haruki; Yamasaki, Ryo; Kusunoki, Susumu; Misawa, Sonoko; Kuwabara, Satoshi; Sato, Yasunori; Yamaguchi, Noriyuki; Nagashima, Kengo; Katayama, K.; Sekiguchi, Yukari; Iwai, Yuta; Yokota, Takanori; Nishida, Yoichiro; Kohara, Nobuo; Kawamoto, Manabu; Ishii, Junko; Kuwahara, Motoi; Suzuki, Hidekazu; Masuda, Ray; Kaneko, Juntaro; Sasaki, Hidenao; Kaida, Kenichi; Suzuki, Shigeaki; Matsui, Naoko; Nagashima, Takahide; Shimizu, Toshio; Hirotani, Makoto; Kadoya, Michiyo; Nakahara, Jin; Shimizu, Junya; Tanaka, Masahiko; Sobue, Gen; Katsuno, Masahisa; Yamaguchi, Hideaki; Ogata, Hideyuki

doi:10.1016/s1474-4422(18)30114-5

Cited by 116 publications

(78 citation statements)

References 26 publications

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“…The highest efficacy is achieved when treatment started within 2 weeks from disease onset [6][7][8][9]. Although recent research has put the complement system under the microscope, no significant alterations to prognosis were accomplished in the past 30 years [10,11].…”

Section: Introductionmentioning

confidence: 99%

Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome

Altmann

Simoni

Kaider

et al. 2020

J Neuroinflammation

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Background: Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome. Methods: Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary. Results: The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (r s = 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability. Conclusions: sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.

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Section: Introductionmentioning

confidence: 99%

Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome

Altmann

Simoni

Kaider

et al. 2020

J Neuroinflammation

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“…The proportion of patients who can walk independently at week 4 was 61% in the eculizumab group and 45% in the placebo group. However, the result cannot be interpreted as statistically significant, because the primary efficacy endpoint could not exceed the predefined response rate 27 . On the other hand, the proportion of patients who could run at week 24 was significantly higher in the eculizumab (74%) than the placebo group (18%).…”

Section: Complement Inhibition In Gbs Patientsmentioning

confidence: 86%

“…Based on these, a phase II clinical trial was conducted to investigate the safety and efficacy of eculizumab, humanized monoclonal antibody to complement C5, for the acute phase of GBS in Japan (Table 1). It enrolled 34 patients with GBS who cannot walk independently within 14 days from the onset 26,27 . Patients were randomly assigned (2:1) to IVIG plus eculizumab (900 mg) or placebo, which were administrated for 4 weeks 26 .…”

Section: Complement Inhibition In Gbs Patientsmentioning

confidence: 99%

Guillain‐Barré syndrome: Novel treatment by complement inhibition

Misawa

Suichi

2020

Clinical & Exp Neuroim

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“…deficiencies in complement components C5-C9) and medical conditions or treatment that may lead to acquired or secondary complement deficiency, such as treatment with eculizumab, a terminal complement pathway inhibitor. [122][123][124][125] For instance, individuals with terminal complement pathway deficiencies are thought to have a 70 0 0-to 10,0 0 0-fold higher risk of IMD versus the general population. 122 Other populations at increased risk of IMD include laboratory workers and Human Immunodeficiency Virus-positive individuals, who have an estimated 184-fold 126 , 127 and 5-fold greater risk of IMD compared with the general population, 128 respectively, as well as migrants and refugees, who live in overcrowded conditions with poor sanitation.…”

Section: Risk Factors For Meningococcal Carriage and Diseasementioning

confidence: 99%

Prevention and control of meningococcal disease: Updates from the Global Meningococcal Initiative in Eastern Europe

Bai

Borrow

Bukovski

et al. 2019

Journal of Infection

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The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a GMI meeting was held with a multidisciplinary group of experts and representatives from countries within Eastern Europe. Across the countries represented, IMD surveillance is largely in place, with incidence declining in recent decades and now generally at < 1 case per 10 0,0 0 0 persons per year. Predominating serogroups are B and C, followed by A, and cases attributable to serogroups W, X and Y are emerging. Available vaccines differ between countries, are generally not included in immunization programs and provided to high-risk groups only. Available vaccines include both conjugate and polysaccharide vaccines; however, current data and GMI recommendations advocate the use of conjugate vaccines, where possible, due to the ability to interrupt the acquisition of carriage. Ongoing carriage studies are expected to inform vaccine effectiveness and immunization schedules. Additionally, IMD prevention and control should be guided by monitoring outbreak progression and the emergence and international spread of strains and antibiotic resistance through use of genomic analyses and implementation of World Health Organization initiatives. Protection of high-risk * Corresponding author.

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

Cited by 116 publications

References 26 publications

Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome

Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome

Guillain‐Barré syndrome: Novel treatment by complement inhibition

Prevention and control of meningococcal disease: Updates from the Global Meningococcal Initiative in Eastern Europe

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