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

Walgaard, C.; Jacobs, B.C.; Lingsma, H.F.; Steyerberg, E.W.; Berg, B. van den; Doets, A.Y.; ... ; Dutch GBS Study Grp (2021)

Article / Letter to editor

Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre 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-Barre syndrome with a predicted poor outcome.Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre 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-Barre 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-Barre 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.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-Barre 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-Barre 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-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

• All authors: Walgaard, C.; Jacobs, B.C.; Lingsma, H.F.; Steyerberg, E.W.; Berg, B. van den; Doets, A.Y.; Leonhard, S.E.; Verboon, C.; Huizinga, R.; Drenthen, J.; Arends, S.; Budde, I.K.; Kleyweg, R.P.; Kuitwaard, K.; Meulen, M.F.G. van der; Samijn, J.P.A.; Vermeij, F.H.; Kuks, J.B.M.; Dijk, G.W. van; Wirtz, P.W.; Eftimov, F.; Kooi, A.J. van der; Garssen, M.P.J.; Gijsbers, C.J.; Rijk, M.C. de; Visser, L.H.; Blom, R.J.; Linssen, W.H.J.P.; Kooi, E.L. van der; Verschuuren, J.J.G.M.; Koningsveld, R. van; Dieks, R.J.G.; Gilhuis, H.J.; Jellema, K.; Ree, T.C. van der; Bienfait, H.M.E.; Faber, C.G.; Lovenich, H.; Engelen, B.G.M. van; Groen, R.J.; Merkies, I.S.J.; Oosten, B.W. van; Pol, W.L. van der; Meulen, W.D.M. van der; Badrising, U.A.; Stevens, M.; Breukelman, A.J.J.; Zwetsloot, C.P.; Graaff, M.M. van der; Wohlgemuth, M.; Hughes, R.A.C.; Cornblath, D.R.; Doorn, P.A. van; Dutch GBS Study Grp
• Date: 2021-04-01
• Journal: The Lancet Neurology
• Volume: 20
• Issue: 4
• Pages: 275 - 283