Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial. Issue 4 (April 2021)

• Record Type: Journal Article
• Authors: Walgaard, Christa; Jacobs, Bart C; Lingsma, Hester F; Steyerberg, Ewout W; van den Berg, Bianca; Doets, Alexandra Y; Leonhard, Sonja E; Verboon, Christine; Huizinga, Ruth; Drenthen, Judith; Arends, Samuel; Budde, Ilona Kleine; Kleyweg, Ruud P; Kuitwaard, Krista; van der Meulen, Marjon F G; Samijn, Johnny P A; Vermeij, Frederique H; Kuks, Jan B M; van Dijk, Gert W; Wirtz, Paul W; Eftimov, Filip; van der Kooi, Anneke J; Garssen, Marcel P J; Gijsbers, Cees J; de Rijk, Maarten C; Visser, Leo H; Blom, Roderik J; Linssen, Wim H J P; van der Kooi, Elly L; Verschuuren, Jan J G M; van Koningsveld, Rinske; Dieks, Rita J G; Gilhuis, H Job; Jellema, Korné; van der Ree, Taco C; Bienfait, Henriette M E; Faber, Catharina G; Lovenich, Harry; van Engelen, Baziel G M; Groen, Rutger J; Merkies, Ingemar S J; van Oosten, Bob W; van der Pol, W Ludo; van der Meulen, Willem D M; Badrising, Umesh A; Stevens, Martijn; Breukelman, Albert-Jan J; Zwetsloot, Casper P; van der Graaff, Maaike M; Wohlgemuth, Marielle; Hughes, Richard A C; Cornblath, David R; van Doorn, Pieter A; Walgaard, Christa; Jacobs, Bart C.; Lingsma, Hester F.; Steyerberg, Ewout W.; Van den Berg, Bianca; Doets, Alexandra Y.; Leonhard, Sonja E.; Verboon, Christine; Huizinga, Ruth; Drenthen, Judith; Arends, Samuel; Kleine Budde, Ilona; Kleyweg, Ruud P.; Kuitwaard, Krista; Van der Meulen, Marjon F.G.; Samijn, Johnny P.A.; Vermeij, Frederique H.; Kuks, Jan B.M.; Van Dijk, Gert W.; Wirtz, Paul W.; Eftimov, Filip; Van der Kooi, Anneke J.; Garssen, Marcel P.J.; Gijsbers, Cees J.; De Rijk, Maarten C.; Visser, Leo H.; Blom, Roderik J.; Linssen, Wim H.J.P.; Van der Kooi, Elly L.; Verschuuren, Jan J.G.M.; Van Koningsveld, Rinske; Dieks, Rita J.G.; Gilhuis, H. Job; Jellema, Korné; Van der Ree, Taco C.; Bienfait, Henriette M.E.; Faber, Karin G.; Lovenich, Harry; Van Engelen, Baziel G.M.; Groen, Rutger J.; Merkies, Ingemar S.J.; Van Oosten, Bob W.; Van der Pol, W. Ludo; Van der Meulen, Willem D.M.; Badrising, Umesh A.; Stevens, Martijn; Breukelman, Albert-Jan J.; Zwetsloot, Casper P.; Van der Graaff, Maaike M.; Wohlgemuth, Marielle; Hughes, Richard A.C.; Cornblath, David R.; Van Doorn, Pieter A.; Althingh van Geusau, R.B.; Van Boheemen, C.J.M.; Bronner, I.M.; Feenstra, B.; Fokke, C.; Hoogendoorn, T.A.; Van Houten, R.; Hovestad, A.; Jansen, P.J.H.W.; Keuter, E.; Krudde, J.; Linn, F.H.H.; Lion, J.; Manschot, S.M.; Mellema, S.J.; Molenaar, D.S.M.; Nieuwkamp, D.J.; Oenema, D.G.; Van Oostrom, J.C.H.; Van Orshoven, N.P.; Van der Ploeg, R.J.O.; Polman, S.; Ruitenberg, A.; Ruts, L.; Schyns-Soeterboek, A.J.G.M.; Trip, R.;
• Is Part Of: Lancet neurology. Volume 20:Issue 4(2021)
• Page Start: 275
• Page End: 283
• Publication Date: 2021-04
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Nervous System Diseases -- Periodicals; Neurologie -- Périodiques; Neurology; Electronic journals; Periodicals; 616.805
• DOI: 10.1016/S1474-4422(20)30494-4
• Languages: English
• ISSNs: 1474-4422

Abstract

Summary: 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.