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Original research: Second IVIg course in Guillain-Barré syndrome with poor prognosis: the non-randomised ISID study
  1. Christine Verboon1,
  2. Bianca van den Berg1,
  3. David R Cornblath2,
  4. Esmee Venema1,3,
  5. Kenneth C Gorson4,
  6. Michael P Lunn5,
  7. Hester Lingsma3,
  8. Peter Van den Bergh6,
  9. Thomas Harbo7,
  10. Kathleen Bateman8,
  11. Yann Pereon9,
  12. Søren H Sindrup10,
  13. Susumu Kusunoki11,
  14. James Miller12,
  15. Zhahirul Islam13,
  16. Hans-Peter Hartung14,
  17. Govindsinh Chavada15,
  18. Bart C Jacobs1,16,
  19. Richard A C Hughes17,
  20. Pieter A van Doorn1
  21. The IGOS Consortium
    1. 1 Department of Neurology, Erasmus MC, Rotterdam, The Netherlands
    2. 2 Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA
    3. 3 Department of Public Health, Erasmus MC, Rotterdam, The Netherlands
    4. 4 Department of Neurology, St. Elizabeth's Medical Center, Boston, Massachusetts, USA
    5. 5 Department of Neurology, National Hospital for Neurology and Neurosurgery, London, UK
    6. 6 Department of Neurology, University Clinic St. Luc, Leuven, Belgium
    7. 7 Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
    8. 8 Department of Neurology, University of Cape Town, Cape Town, South Africa
    9. 9 Department of Clinical Neurophysiology, Reference Centre for NMD, Nantes University Hospital, Nantes, France
    10. 10 Department of Neurology, Odense University Hospital, Odense, Denmark
    11. 11 Department of Neurology, Kindai University Faculty of Medicine, Osaka, Japan
    12. 12 Department of Neurology, Royal Victoria Infirmary, Newcastle, UK
    13. 13 Department of Laboratory Sciences and Services Division, The International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
    14. 14 Department of Neurology, Heinrich Heine University, Düsseldorf, Germany
    15. 15 Department of Neurology, University of Glasgow, Glasgow, UK
    16. 16 Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
    17. 17 MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery, London, UK
    1. Correspondence to Prof Dr Pieter A van Doorn, Neurology, Erasmus MC, 3000 CA, Rotterdam, The Netherlands; p.a.vandoorn{at}erasmusmc.nl

    Abstract

    Objective To compare disease course in patients with Guillain-Barré syndrome (GBS) with a poor prognosis who were treated with one or with two intravenous immunoglobulin (IVIg) courses.

    Methods From the International GBS Outcome Study, we selected patients whose modified Erasmus GBS Outcome Score at week 1 predicted a poor prognosis. We compared those treated with one IVIg course to those treated with two IVIg courses. The primary endpoint, the GBS disability scale at 4 weeks, was assessed with multivariable ordinal regression.

    Results Of 237 eligible patients, 199 patients received a single IVIg course. Twenty patients received an ‘early’ second IVIg course (1–2 weeks after start of the first IVIg course) and 18 patients a ‘late’ second IVIg course (2–4 weeks after start of IVIg). At baseline and 1 week, those receiving two IVIg courses were more disabled than those receiving one course. Compared with the one course group, the adjusted OR for a better GBS disability score at 4 weeks was 0.70 (95%CI 0.16 to 3.04) for the early group and 0.66 (95%CI 0.18 to 2.50) for the late group. The secondary endpoints were not in favour of a second IVIg course.

    Conclusions This observational study did not show better outcomes after a second IVIg course in GBS with poor prognosis. The study was limited by small numbers and baseline imbalances. Lack of improvement was likely an incentive to start a second IVIg course. A prospective randomised trial is needed to evaluate whether a second IVIg course improves outcome in GBS.

    • Guillain-Barré syndrome
    • poor prognosis
    • treatment
    • second IVIg course
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    Footnotes

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    • Correction notice This article has been corrected since it was published Online First. Table data have been aligned correctly and footnotes adjusted.

    • Collaborators For this study, patients were selected from the following collaborators: J.M. Addington, MD (University of Virginia, Charlottesville, USA); S. Ajroud-Driss, MD (Northwestern University Feinberg, Chicago, USA); G. Antonini, MD (Mental Health and Sensory Organs (NESMOS), Sapienza University, Sant’Andrea Hospital, Rome, Italy); S. Attarian, MD, PhD (CHU Timone, Marseille, France); F.A. Barroso, MD (Instituto de Investigaciones Neurológicas Raúl Carrea, FLENI, Buenos Aires, Argentina); L. Benedetti, MD, PhD (Ospedale Sant’ Andrea La Spezia, La Spezia, Italy); T.E. Bertorini, MD (The University of Tennessee Health Science Center (UTHSC), Memphis, USA); T.H. Brannagan, MD (Columbia University, New York City, USA); C. Briani, MD (University of Padova, Padova, Italy); R. Bhavaraju-Sanka, MD (University Hospital/University of Texas Health Science Center, San Antonio Texas, USA); S. Butterworth, MD (Pinderfields Hospital, Wakefield, UK); C. Casasnovas, MD, PhD (Bellvitge University Hospital – IDIBELL Neurometabolic Diseases Group. CIBERER, Barcelona, Spain); G. Cavaletti, MD (University Milano-Bicocca, Monza, Italy); S. Chen, MD, PhD (Rutgers, Robert Wood Johnson University Hospital, New Brunswick, USA); K.G. Claeys, MD, PhD (1. University Hospitals Leuven, Leuven, Belgium, 2. KU Leuven, Leuven, Belgium); J.S. Cosgrove, MD (Leeds General Infirmary, Leeds, UK); A. Davidson, MD (University of Glasgow, Glasgow, UK); E. Dardiotis, MD (University of Thessaly, Hospital of Larissa, Larissa, Greece); C. Dornonville de la Cour, MD (National Hospital Copenhagen, Copenhagen, Denmark); C.G. Faber, MD, PhD (Maastricht University Medical Centre, Maastricht, The Netherlands); T.E. Feasby, MD (University of Calgary, Calgary, Canada); T. Fujioka, MD (Toho University Medical Center, Tokyo, Japan); G. Galassi, MD (University Hospital of Modena, Modena, Italy); J.M. Gilchrist, MD (Soulthern Illinois University School of Medicine, Springfield, USA); N. A. Goyal, MD (University of California, Irvine, USA); V. Granit, MD (Montefiore Medical, Center, New York, USA); G. Gutiérrez-Gutiérrez, MD (Hospital Universitario Infanta Sofia, San Sebastian, Spain); R.D.M. Hadden, MD, PhD (King’s College Hospital, London, UK); J.K.L. Holt, PhD, FRCP (The Walton Centre, Liverpool, UK); M. Htut, MD (St. George’s Hospital, London, UK); I. Jericó Pascual, MD, PhD (Complejo Hospitalario de Navarra, Pamplona, Spain); S. Karafiath, MD (University of Utah School of Medicine, Salt Lake City, USA); H.D. Katzberg, MD (University of Toronto, Toronto, Canada); L. Kiers, MD (University of Melbourne, Royal Melbourne Hospital, Parkville, Australia); B.C. Kieseier, MD (Heinrich Heine University, Düsseldorf, Germany); K. Kimpinski, MD (University Hospital, LHSC, London-Ontario, Canada); S. Kuwabara, MD, PhD (Chiba University, Chiba, Japan); J.Y. Kwan, MD (University of Maryland School of Medicine, Baltimore, USA); S.S. Ladha, MD (Barrow Neurology Clinics, Phoenix, Arizona, USA); V. Lawson, MD (Wexner Medical Center at The Ohio State University, Columbus, USA); H. Lehmann, MD, PhD (University Hospital of Cologne, Universitätsklinikum Köln, Cologne, Germany); H. Manji, MD, FRCP (Ipswich Hospital, Ipswich, UK); G.A. Marfia, MD (Neurological Clinic, Policlinico Tor Vergata, Rome, Italy); C. Márquez Infante, MD (Hospital Universitario Virgen del Rocio, Seville, Spain); M.G. Mattiazzi, MD (Hospital Militar Central, Buenos Aires, Argentina); C.J. McDermott, MD (Royal Hallamshire Hospital, NIHR Clinical, Sheffield, UK); M.S. Monges, MD (Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina); G. Morís de la Tassa, MD (Hospital Universitario Central de Asturias, Asturias, Spain); C. Nascimbene, MD, PhD (Luigi Sacco Hospital, Milan, Italy); E. Nobile Orazio, MD, PhD (Milan University, Humanitas Clinicala and Research Institute Milan, Italy); R.J. Nowak, MD (Yale University School of Medicine, New Haven, USA); M. Osei-Bonsu (James Cook University Hospital, Middlesbrough, UK); J. Pardo Fernandez (Hospital Clínico de Santiago, Santiago de Compostela (A Coruña), Spain); L. Querol Gutierrez, MD, PhD (Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain); R. Reisin (Hospital Britanico, Buenos Aires, Argentina); S. Rinaldi, MBChB, PhD (University of Oxford R.C. Roberts, MD (Addenbrooke’s Hospital Cambridge, Cambridge, UK); I. Rojas-Marcos, MD (Hospital Univesitario Reina Sofia, Cordoba, Spain); S.A. Rudnicki, MD (University of Arkansas, Fayetteville, USA); A. Schenone, MD, PhD (1. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Infantile Sciences (DINOGMI), University of Genova, Genova, Italy 2. IRCCS Policlinico San Martino, Genova, Italy); M.J. Sedano Tous, MD (Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Spain); N. Shahrizaila, MD (Neurology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Malaya); K. Sheikh, MD, PhD (The University of Texas Health Science Center at Houston, Houston, USA); N.J. Silvestri, MD (Buffalo General Medical Center, Buffalo NY, USA); C.L. Sommer, MD (Universitätsklinikum Würzburg, Würzburg, Germany); J.D. Varrato, DO (Lehigh Valley Health Network, Allentown, USA); J. Verschuuren, MD, PhD (Leiden University Medical Centre, Leiden, The Netherlands); M.V. Vytopil, MD, PhD (Tufts University School of Medicine Lahey Hospital W. Waheed, MD (University of Vermont Medical Center, Burlington, USA); L. Zhou, MD, PhD (Icahn School of Medicine at Mount Sinai, New York, USA).Other collaborators were:U.A. Badrising, MD, PhD (Leiden University Medical Centre, Leiden, The Netherlands); I.R. Bella, MD (University of Mass Medical School, Worcester, USA); C. Bunschoten, MD, PhD candidate (Erasmus University Medical Centre, Rotterdam, The Netherlands); J. Bürmann, MD, Universitätsklinikum des Saarlandes, Homburg, Germany); M. Busby, MD (Leeds General Infirmary, Bradford, UK); C.C. Chao, MD, PhD (National Taiwan University Hospital, Taipei, Taiwan); M.E. Conti, MD (University Hospital Clinicas, Buenos Aires, Argentina); M.C. Dalakas, MD (1. Thomas Jefferson University, Philadelphia, USA, 2. National and Kapodistrian University of Athens, Athens, Greece); P. Van Damme, MD, PhD (University Hospital Leuven, Leuven, Belgium); A. Doets, MD, PhD candidate (Erasmus University Medical Centre, Rotterdam, the Netherlands); G.W. van Dijk, MD (Canisius Wilhelmina Hospital, Nijmegen, The Netherlands); M.M. Dimachkie, MD (University of Kansas Medical Center, Kansas City, USA); K. Doppler, MD (Universitätsklinikum Würzburg, Würzburg, Germany); A. Echaniz-Laguna, MD (Hopital de Hautepierre, Strasbourgh, France); F. Eftimov, MD, PhD (Amsterdam University Medical Centre, Amsterdam, The Netherlands); R. Fazio, MD (Scientific Institute San Raffaele, Milan, Italy); C. Fokke, MD (Gelre Hospital, Zutphen and Apeldoorn, The Netherlands); E.A. Fulgenzi, MD (Hospital Cesar Milstein Buenos Aires, Buenos Aires, Argentina); M.P.J. Garssen, MD, PhD (Jeroen Bosch Hospital, ‘s Hertogenbosch, Zaltbommel and Drunen, The Netherlands); C.J. Gijsbers, MD (Vlietland Hospital, Schiedam, The Netherlands); J. Gilhuis, MD, PhD (Reinier de Graaf Gasthuis, Delft, The Netherlands); A. Grapperon, MD (CHU Timone, Marseille, France); S.T. Hsieh, MD, PhD (National Taiwan University Hospital, Taipei, Taiwan); I. Illa, MD, PhD (Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain); B. Islam, MD, PhD (International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh); K. Jellema, MD, PhD (Haaglanden Medisch Centrum, The Hague, The Netherlands); K. Kaida, MD, PhD (National Defense Medical College, Saitama, Japan); N. Kokubun, MD (Dokkyo Medical University, Tochigi, Japan); N. Kolb, MD (University of Vermont, Burlington VT, USA); R. van Koningsveld, MD, PhD (Elkerliek Hospital, Helmond and Deurne, The Netherlands); A.J. van der Kooi, MD, PhD (Amsterdam University Medical Centre, Amsterdam, The Netherlands); K. Kuitwaard, MD, PhD (Albert Schweitzer Hospital, Dordrecht, The Netherlands); L. Landschoff Lassen, MD (Glostrup Hospital, Glostrup, Denmark); S.E. Leonhard, MD, PhD candidate (Erasmus University Medical Centre, Rotterdam, the Netherlands); M. Mandarakas, MD, PhD (Erasmus University Medical Centre, Rotterdam, the Netherlands); E. Martinez Hernandez, MD (Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Barcelona, Spain); Q.D. Mohammad, MD, PhD (National Institute of Neurosciences and Hospital, Dhaka, Bangladesh); M. Pulley, MD (University of Florida, Jacksonville, USA); Y.A. Rajabally, MD, PhD (Queen Elizabeth Hospital, Birmingham, UK); S.W. Reddel, MD, PhD (Concord Repatriation General Hospital, Sydney, Australia); T. van der Ree, MD (Westfriesgasthuis, Hoorn, The Netherlands); J. Roodbol, MD, PhD candidate (Erasmus University Medical Centre, Rotterdam, the Netherlands); G.M. Sachs, MD (University of Rhode Island, Providence, USA); J.P.A. Samijn, MD, PhD (Maasstad Hospital, Rotterdam, The Netherlands); L. Santoro, MD, PhD (University Federico II, Napels, Italy); B. Stein, MD (St. Joseph’s Regional Medical Center, Paterson, USA); F.H. Vermeij, MD (Franciscus Gasthuis, Rotterdam, The Netherlands); L.H. Visser, MD, PhD (Elisabeth-TweeSteden Hospital, Tilburg and Waalwijk, The Netherlands); H.J. Willison, MD, PhD (University of Glasgow, Glasgow, UK); P. Wirtz, MD, PhD (HagaZiekenhuis, The Hague, The Netherlands); S.A. Zivkovich, MD, PhD (University of Pittsburgh Medical Center, Pittsburgh, USA).

    • Contributors CV: Study concept and design, patient inclusion, acquisition of data, analysis and interpretation of the data, drafted and revised the manuscript for intellectual content. Member of IGOS Coordinating Center, IGOS Country Coordinator. BvdB: Study concept and design, patient inclusion, acquisition of data, interpretation of the data, revised the manuscript for intellectual content. Member of IGOS Coordinating Center, IGOS Country Coordinator. DRC: Study concept and design, interpretation of the data, revised the manuscript for intellectual content. Member of the IGOS Steering Committee. EV and HL: Analysis and interpretation of the data, revised the manuscript for intellectual content. KCG: Study concept and design, interpretation of the data, revised the manuscript for intellectual content. Member of the IGOS Steering Committee, IGOS Country Coordinator. MPL: Study concept and design, patient inclusion, acquisition of data, interpretation of the data, revised the manuscript for intellectual content. PVdB, TH, KB, YP, SK, ZI, GC: Patient inclusion, acquisition of data, interpretation of the data, revised the manuscript for intellectual content. IGOS Country Coordinator. SHS, JM: Patient inclusion, acquisition of data, interpretation of the data, revised the manuscript for intellectual content. H-PH: Study concept and design, interpretation of the data, revised the manuscript for intellectual content. Member of the IGOS Steering Committee. BCJ: Study concept and design, patient inclusion, acquisition of data, interpretation of the data, revised the manuscript for intellectual content. Member of the IGOS Steering Committee, Member of the IGOS Coordinating Center, IGOS Country coordinator. RH: Study concept and design, interpretation of the data, revised the manuscript for intellectual content. Member of the IGOS Steering Committee. PvD: Study concept and design, patient inclusion, acquisition of data, analysis and interpretation of the data, drafted and revised the manuscript for intellectual content. Member of the IGOS Steering Committee.

    • Funding This study is mainly funded by Grifols. Other sponsors of IGOS are GBS-CIDP Foundation International, GAIN Charity, Erasmus University Medical Centre, Glasgow University, CSL Behring and Annexon.

    • Competing interests CV, BvdB, EV, HL, KB, SHS, ZI report no disclosures. DRC is a consultant for Acetylon, Alcobra Pharma, Alnylam Pharmaceuticals, Annexon Biosciences, Akros Pharma, Biotest Pharmaceuticals, Boehringer Ingelheim, Cigna HealthManagement, CSL Behring, DP Clinical, Grifols, Hansa Medical, Karos Pharmaceuticals, Neurocrine Biosciences, Novartis, Octapharma, Pharnext, Seattle Genetics, Sun Pharmaceuticals, and Syntimmune. He is on the data and safety monitoring board for Sanofi, Pledpharma, Pfizer, Johnson Roche, Sanofi Genzyme, Teva,TG Therapeutics and UCB. GC has received honoraria from CSL Behring. BCJ has received funding for research projects from Prinses Beatrix Spierfonds, Horizon 2020,GBS-CIDP Foundation International, Grifols, CSL Behring and Annexon. He is on the Medical Advisory Board for the GBS-CIDP Foundation International, and a member of the Inflammatory Neuropathy Consortium. RH has current consultancies with LFB and former consultancies with Novartis. PvD has received honoraria for consulting, lectures and serving on steering committees from Octapharma, Kedrion, CSL Behring, Grifols, and Hansa (all honoraria to departmental research fund), and is currently receiving grants from Prinses Beatrix Spierfonds, Sanquin Blood supply, Shire and Grifols. He is President Elect of the Peripheral Nerve Society, member of the Inflammatory Neuropathy Consortium, Medical Advisory Board for the GBS-CIDP Foundation International, editorial board for the Journal of the Neurological Sciences and Journal of Neuromuscular Diseases. He is PI of the RCT investigating the effect of methylprednisolone in GBS (MP/IVIg RCT in GBS) and the RCT investigating the effect of a second dose IVIg in GBS (SID-GBS study).

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request.

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