TY - JOUR
T1 - Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS)
T2 - a double-blind, randomised, placebo-controlled trial
AU - Dutch GBS Study Group
AU - Walgaard, Christa
AU - Jacobs, Bart C.
AU - Lingsma, Hester F.
AU - Steyerberg, Ewout W.
AU - van den Berg, Bianca
AU - Doets, Alexandra Y.
AU - Leonhard, Sonja E.
AU - Verboon, Christine
AU - Huizinga, Ruth
AU - Drenthen, Judith
AU - Arends, Samuel
AU - Budde, Ilona Kleine
AU - Kleyweg, Ruud P.
AU - Kuitwaard, Krista
AU - van der Meulen, Marjon F.G.
AU - Samijn, Johnny P.A.
AU - Vermeij, Frederique H.
AU - Kuks, Jan B.M.
AU - van Dijk, Gert W.
AU - Wirtz, Paul W.
AU - Eftimov, Filip
AU - van der Kooi, Anneke J.
AU - Garssen, Marcel P.J.
AU - Gijsbers, Cees J.
AU - de Rijk, Maarten C.
AU - Visser, Leo H.
AU - Blom, Roderik J.
AU - Linssen, Wim H.J.P.
AU - van der Kooi, Elly L.
AU - Verschuuren, Jan J.G.M.
AU - van Koningsveld, Rinske
AU - Dieks, Rita J.G.
AU - Gilhuis, H. Job
AU - Jellema, Korné
AU - van der Ree, Taco C.
AU - Bienfait, Henriette M.E.
AU - Faber, Catharina G.
AU - Lovenich, Harry
AU - van Engelen, Baziel G.M.
AU - Groen, Rutger J.
AU - Merkies, Ingemar S.J.
AU - van Oosten, Bob W.
AU - van der Pol, W. Ludo
AU - van der Meulen, Willem D.M.
AU - Badrising, Umesh A.
AU - Stevens, Martijn
AU - Breukelman, Albert Jan J.
AU - Zwetsloot, Casper P.
AU - van der Graaff, Maaike M.
AU - Cornblath, David R.
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
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U2 - 10.1016/S1474-4422(20)30494-4
DO - 10.1016/S1474-4422(20)30494-4
M3 - Article
C2 - 33743237
AN - SCOPUS:85102562821
SN - 1474-4422
VL - 20
SP - 275
EP - 283
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 4
ER -