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 - 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 - van der Graaff, Maaike M.
AU - van der Kooi, Anneke J.
AU - van der Graaff, Maaike M.
AU - Zwetsloot, Casper P.
N1 - Funding Information: BCJ reports grants from Baxalta, Grifols, CSL-Behring, Annexon, Prinses-Beatrix Spierfonds, Guillain-Barré syndrome/chronic inflammatory demyelinating polyneuropathy (GBS/CIDP) Foundation International, Hansa Biopharma, and EU's Horizon 2020, outside the submitted work. AYD declares that her host institution, the Erasmus MC, pays her salary with a fund from Annexon Biosciences (January, 2017), a pharmaceutical company that develops complement inhibitors for Guillain-Barré syndrome. Neither her PhD research nor her employment is contingent on this funding, and AYD has no control over the use of the funds. AYD has also received an honorarium for a lecture from CSL Behring (November, 2018). The money was paid directly to the Erasmus MC and AYD did not financially benefit from this honorarium. KK reports grants from Baxalta now part of Shire/Takeda, outside the submitted work. RH reports grants from Grifols, and GBS/CIDP Foundation International, outside the submitted work. AJvdK reports a grant from CSL Behring, outside the submitted work. FE reports grants from CSL Behring, Kedrion, Terumo BCT, and Takeda Pharmaceutical Company, outside the submitted work. Grants were paid to their institution and were used for investigator-initiated studies within INCbase, an international CIDP registry. He also received consultancy fees from UCB pharma, paid to his institution, outside the submitted work. CGF reports grants from EU's Horizon 2020 research and innovation programme, Marie Sklodowska-Curie grant for PAIN-Net, Molecule-to-man pain network (grant number 721841), Prinses Beatrix Spierfonds, Grifols, and Lamepro for a trial on intravenous immunoglobulin in small fibre neuropathy, was a member on steering committees and an advisory board for studies in small fibre neuropathy of Biogen/Convergence and Vertex, outside the submitted work. ISJM reports grants from Talecris Talents program, GBS/CIDP Foundation International and FP7 EU program, outside the submitted work; Furthermore, a research foundation at the University of Maastricht received honoraria on behalf of him for participation in steering committees of the Talecris Immune Globulin Intravenous For Chronic Inflammatory Demyelinating Polyneuropathy Study, Commonwealth Serum Laboratories, Behring, Octapharma, LFB, Novartis, Union Chimique Belge, outside the submitted work. UAB reports financial compensation for costs made to include patients in a trial from Novartis, outside the submitted work. RACH reports personal fees from LFB, Hansa Biopharma, and Sanofi, outside the submitted work and is a medical patron of GAIN. DRC reports consulting for Amgen, Annexon Biosciences, argenx SE, Biotest Pharmaceuticals, Cigna Health Management, CSL Behring, CytomX Therapeutics, Grifols, New Enterprise Associates, Octapharma, Pfizer, Pharnext, Polyneuron Pharmaceuticals, Seattle Genetics, Syntimmune, and UCB. DRC was on the Data Safety Monitoring Board for the following: Alnylam Pharmaceuticals, PledPharma, Momenta Pharma, Hansa Medical, and Mitsubishi Tanabe Pharma Corporation. DRC was involved with technology licensing for AstraZeneca Pharmaceuticals, LP Pharmaceuticals (Xiamen), Genentech, Levicept, Seattle Genetics, Merrimack Pharmaceuticals, and Disarm Therapeutics, outside the submitted work. PAvD reports grants from Sanquin Blood Supply and Prinses Beatrix Spierfonds, during the conduct of the study; and grants from Grifols, Takeda, Annexion, Argenx, Commonwealth Serum Laboratories, Octapharma, and Hansa, outside the submitted work. All grants were paid to the institution and used for investigator-initiated studies. All other authors declare no competing interests. Publisher Copyright: © 2021 Elsevier Ltd
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-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.
UR - http://www.scopus.com/inward/record.url?scp=85102562821&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S1474-4422(20)30494-4
DO - https://doi.org/10.1016/S1474-4422(20)30494-4
M3 - Article
C2 - 33743237
SN - 1474-4422
VL - 20
SP - 275
EP - 283
JO - Lancet neurology
JF - Lancet neurology
IS - 4
ER -