Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial.

Abstract

BACKGROUND:

Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barré syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barré syndrome with a predicted poor outcome.

METHODS:

In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (≥12 years) with Guillain-Barré syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of ≥6) according to the modified Erasmus Guillain-Barré syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barré syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. This study is registered with the Netherlands Trial Register, NTR 2224/NL2107.

FINDINGS:

Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barré syndrome disability score at 4 weeks was 1·4 (95% CI 0·6-3·3; p=0·45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation).

INTERPRETATION:

Our study does not provide evidence that patients with Guillain-Barré syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barré syndrome.

FUNDING:

Prinses Beatrix Spierfonds and Sanquin Plasma Products.

• Authors: Christa Walgaard, Bart C Jacobs, Hester F Lingsma, Ewout W Steyerberg, Bianca van den Berg, Alexandra Y Doets, Sonja E Leonhard, Christine Verboon, Ruth Huizinga, Judith Drenthen, Samuel Arends, Ilona Kleine Budde, Ruud P Kleyweg, Krista Kuitwaard, Marjon F G van der Meulen, Johnny P A Samijn, Frederique H Vermeij, Jan B M Kuks, Gert W van Dijk, Paul W Wirtz, Filip Eftimov, Anneke J van der Kooi, Marcel P J Garssen, Cees J Gijsbers, Maarten C de Rijk, Leo H Visser, Roderik J Blom, Wim H J P Linssen, Elly L van der Kooi, Jan J G M Verschuuren, Rinske van Koningsveld, Rita J G Dieks, H Job Gilhuis, Korné Jellema, Taco C van der Ree, Henriette M E Bienfait, Catharina G Faber, Harry Lovenich, Baziel G M van Engelen, Rutger J Groen, Ingemar S J Merkies, Bob W van Oosten, W Ludo van der Pol, Willem D M van der Meulen, Umesh A Badrising, Martijn Stevens, Albert-Jan J Breukelman, Casper P Zwetsloot, Maaike M van der Graaff, Marielle Wohlgemuth, Richard A C Hughes, David R Cornblath, Pieter A van Doorn, Dutch GBS Study Group
• Journal: The Lancet. Neurology (Lancet Neurol) Vol. 20 Issue 4 Pg. 275-283 (04 2021) ISSN: 1474-4465 [Electronic] England
• PMID: 33743237 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Immunoglobulins, Intravenous

Topics

• Adult
• Aged
• Double-Blind Method
• Female
• Guillain-Barre Syndrome (drug therapy)
• Humans
• Immunoglobulins, Intravenous (administration & dosage)
• Male
• Middle Aged
• Netherlands
• Prognosis
• Treatment Outcome