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

C. Walgaard; B.C. Jacobs; H.F. Lingsma; E.W. Steyerberg; B. van den Berg; A.Y. Doets; S.E. Leonhard; C. Verboon; R. Huizinga; J. Drenthen; S. Arends; I.K. Budde; R.P. Kleyweg; K. Kuitwaard; M.F.G. van der Meulen; J.P.A. Samijn; F.H. Vermeij; J.B.M. Kuks; G.W. van Dijk; P.W. Wirtz; F. Eftimov; A.J. van der Kooi; M.P.J. Garssen; C.J. Gijsbers; M.C. de Rijk; L.H. Visser; R.J. Blom; W.H.J.P. Linssen; E.L. van der Kooi; J.J.G.M. Verschuuren; R. van Koningsveld; R.J.G. Dieks; H.J. Gilhuis; K. Jellema; T.C. van der Ree; H.M.E. Bienfait; C.G. Faber; H. Lovenich; B.G.M. van Engelen; R.J. Groen; I.S.J. Merkies; B.W. van Oosten; W.L. van der Pol; W.D.M. van der Meulen; U.A. Badrising; M. Stevens; A.J.J. Breukelman; C.P. Zwetsloot; M.M. van der Graaff; M. Wohlgemuth; Dutch GBS Study Grp; Pieter Antoon van Doorn

doi:10.1016/S1474-4422(20)30494-4

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

C. Walgaard, B.C. Jacobs, H.F. Lingsma, E.W. Steyerberg, B. van den Berg, A.Y. Doets, S.E. Leonhard, C. Verboon, R. Huizinga, J. Drenthen, S. Arends, I.K. Budde, R.P. Kleyweg, K. Kuitwaard, M.F.G. van der Meulen, J.P.A. Samijn, F.H. Vermeij, J.B.M. Kuks, G.W. van Dijk, P.W. WirtzF. Eftimov, A.J. van der Kooi, M.P.J. Garssen, C.J. Gijsbers, M.C. de Rijk, L.H. Visser, R.J. Blom, W.H.J.P. Linssen, E.L. van der Kooi, J.J.G.M. Verschuuren, R. van Koningsveld, R.J.G. Dieks, H.J. Gilhuis, K. Jellema, T.C. van der Ree, H.M.E. Bienfait, C.G. Faber, H. Lovenich, B.G.M. van Engelen, R.J. Groen, I.S.J. Merkies, B.W. van Oosten, W.L. van der Pol, W.D.M. van der Meulen, U.A. Badrising, M. Stevens, A.J.J. Breukelman, C.P. Zwetsloot, M.M. van der Graaff, M. Wohlgemuth, Dutch GBS Study Grp, Pieter Antoon van Doorn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	275-283
Number of pages	9
Journal	Lancet Neurology
Volume	20
Issue number	4
DOIs	https://doi.org/10.1016/S1474-4422(20)30494-4
Publication status	Published - 1 Apr 2021

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10.1016/S1474-4422(20)30494-4

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Walgaard, C., Jacobs, B. C., Lingsma, H. F., Steyerberg, E. W., van den Berg, B., Doets, A. Y., Leonhard, S. E., Verboon, C., Huizinga, R., Drenthen, J., Arends, S., Budde, I. K., Kleyweg, R. P., Kuitwaard, K., van der Meulen, M. F. G., Samijn, J. P. A., Vermeij, F. H., Kuks, J. B. M., van Dijk, G. W., ... van Doorn, P. A. (2021). Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial. Lancet Neurology, 20(4), 275-283. https://doi.org/10.1016/S1474-4422(20)30494-4

@article{7e8b45d8d9f64d008dcbf68135f7c6a2,

title = "Second intravenous immunoglobulin dose in patients with Guillain-Barr{\'e} 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-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.",

author = "C. Walgaard and B.C. Jacobs and H.F. Lingsma and E.W. Steyerberg and {van den Berg}, B. and A.Y. Doets and S.E. Leonhard and C. Verboon and R. Huizinga and J. Drenthen and S. Arends and I.K. Budde and R.P. Kleyweg and K. Kuitwaard and {van der Meulen}, M.F.G. and J.P.A. Samijn and F.H. Vermeij and J.B.M. Kuks and {van Dijk}, G.W. and P.W. Wirtz and F. Eftimov and {van der Kooi}, A.J. and M.P.J. Garssen and C.J. Gijsbers and {de Rijk}, M.C. and L.H. Visser and R.J. Blom and W.H.J.P. Linssen and {van der Kooi}, E.L. and J.J.G.M. Verschuuren and {van Koningsveld}, R. and R.J.G. Dieks and H.J. Gilhuis and K. Jellema and {van der Ree}, T.C. and H.M.E. Bienfait and C.G. Faber and H. Lovenich and {van Engelen}, B.G.M. and R.J. Groen and I.S.J. Merkies and {van Oosten}, B.W. and {van der Pol}, W.L. and {van der Meulen}, W.D.M. and U.A. Badrising and M. Stevens and A.J.J. Breukelman and C.P. Zwetsloot and {van der Graaff}, M.M. and M. Wohlgemuth and {Dutch GBS Study Grp} and {van Doorn}, {Pieter Antoon}",

year = "2021",

month = apr,

day = "1",

doi = "10.1016/S1474-4422(20)30494-4",

language = "English",

volume = "20",

pages = "275--283",

journal = "Lancet Neurology",

issn = "1474-4422",

publisher = "Elsevier Science",

number = "4",

}

Walgaard, C, Jacobs, BC, Lingsma, HF, Steyerberg, EW, van den Berg, B, Doets, AY, Leonhard, SE, Verboon, C, Huizinga, R, Drenthen, J, Arends, S, Budde, IK, Kleyweg, RP, Kuitwaard, K, van der Meulen, MFG, Samijn, JPA, Vermeij, FH, Kuks, JBM, van Dijk, GW, Wirtz, PW, Eftimov, F, van der Kooi, AJ, Garssen, MPJ, Gijsbers, CJ, de Rijk, MC, Visser, LH, Blom, RJ, Linssen, WHJP, van der Kooi, EL, Verschuuren, JJGM, van Koningsveld, R, Dieks, RJG, Gilhuis, HJ, Jellema, K, van der Ree, TC, Bienfait, HME, Faber, CG, Lovenich, H, van Engelen, BGM, Groen, RJ, Merkies, ISJ, van Oosten, BW, van der Pol, WL, van der Meulen, WDM, Badrising, UA, Stevens, M, Breukelman, AJJ, Zwetsloot, CP, van der Graaff, MM, Wohlgemuth, M, Dutch GBS Study Grp & van Doorn, PA 2021, 'Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial', Lancet Neurology, vol. 20, no. 4, pp. 275-283. https://doi.org/10.1016/S1474-4422(20)30494-4

TY - JOUR

T1 - Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial

AU - Walgaard, C.

AU - Jacobs, B.C.

AU - Lingsma, H.F.

AU - Steyerberg, E.W.

AU - van den Berg, B.

AU - Doets, A.Y.

AU - Leonhard, S.E.

AU - Verboon, C.

AU - Huizinga, R.

AU - Drenthen, J.

AU - Arends, S.

AU - Budde, I.K.

AU - Kleyweg, R.P.

AU - Kuitwaard, K.

AU - van der Meulen, M.F.G.

AU - Samijn, J.P.A.

AU - Vermeij, F.H.

AU - Kuks, J.B.M.

AU - van Dijk, G.W.

AU - Wirtz, P.W.

AU - Eftimov, F.

AU - van der Kooi, A.J.

AU - Garssen, M.P.J.

AU - Gijsbers, C.J.

AU - de Rijk, M.C.

AU - Visser, L.H.

AU - Blom, R.J.

AU - Linssen, W.H.J.P.

AU - van der Kooi, E.L.

AU - Verschuuren, J.J.G.M.

AU - van Koningsveld, R.

AU - Dieks, R.J.G.

AU - Gilhuis, H.J.

AU - Jellema, K.

AU - van der Ree, T.C.

AU - Bienfait, H.M.E.

AU - Faber, C.G.

AU - Lovenich, H.

AU - van Engelen, B.G.M.

AU - Groen, R.J.

AU - Merkies, I.S.J.

AU - van Oosten, B.W.

AU - van der Pol, W.L.

AU - van der Meulen, W.D.M.

AU - Badrising, U.A.

AU - Stevens, M.

AU - Breukelman, A.J.J.

AU - Zwetsloot, C.P.

AU - van der Graaff, M.M.

AU - Wohlgemuth, M.

AU - Dutch GBS Study Grp

AU - van Doorn, Pieter Antoon

PY - 2021/4/1

Y1 - 2021/4/1

N2 - 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.

AB - 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.

U2 - 10.1016/S1474-4422(20)30494-4

DO - 10.1016/S1474-4422(20)30494-4

M3 - Article

SN - 1474-4422

VL - 20

SP - 275

EP - 283

JO - Lancet Neurology

JF - Lancet Neurology

IS - 4

ER -