Observational Data as External Control Arm to Study the Effectiveness of New Therapies for Guillain-Barré Syndrome
Year: 2026
Type: article
Abstract: Background and ObjectivesDespite treatment with IV immunoglobulins (IVIg) and plasma exchange, many patients with Guillain-Barré syndrome (GBS) have poor outcome or considerable residual complaints. Randomized controlled trials (RCTs) are challenging for many reasons while increasingly available real-world data (RWD) might provide new opportunities to study treatment effectiveness and accelerate research progress. This study assessed the potential to construct a control group from observational data to compare effectiveness of new treatments for GBS with the current standard treatment. MethodsAs a proof of concept, we emulated the Second IVIg Dose (SID)-GBS RCT by using data from the prospective observational International GBS Outcome Study (IGOS). Patients treated with SID in the RCT (intervention) were compared with IGOS patients treated with a single course of IVIg (controls), selected based on the SID-GBS eligibility criteria. Included were patients aged 12 years and older from Europe/America with a poor prognosis and treated with IVIg 2 g/kg in 2–5 days started <2 weeks from onset of weakness. A propensity score was calculated based on known prognostic baseline factors, including age, preceding diarrhea, limb weakness, and the GBS Disability Scale (GBS-DS). Each patient treated with SID was matched with up to 3 IGOS controls using nearest neighbor matching on their propensity score. The primary outcome was the GBS-DS at week 4, analyzed with ordinal logistic regression. ResultsAfter applying the eligibility criteria, 187 of 1907 IGOS patients (10%) were available for matching. Before matching, substantial baseline imbalances existed for age, preceding diarrhea, and GBS-DS. Ninety-six percent (47/49) of patients treated with SID were matched to 61% (114/187) IGOS controls, which resulted in an adequate balance in all included baseline variables. The odds ratio for improvement on the GBS-DS at week 4 was 0.8 (95% CI 0.4–1.6) (>1 SID favorable). DiscussionThis study demonstrated the feasibility of a design to emulate a RCT in GBS by selecting external controls from RWD. Almost all patients treated with SID in the RCT could be matched to RWD controls with adequate balance. As in the RCT, SID was not associated with better outcome. This design offers promising opportunities for comparative studies of new treatments in GBS and other rare neurologic diseases.
Source: Neurology Open Access
Authors: Linda W.G. Luijten, Eveline J.A. Wiegers, Laura Christine De Koning, Shahram Attarian, David R. Cornblath, Amy I. Davidson, Kenneth C. Gorson, Thomas Harbo, Hans-Peter Hartung, Satoshi Kuwabara, Eduardo Nobile-Orazio, Christine Verboon, Christa Walgaard, Hester F. Lingsma, Pieter A. Van Doorn, Bart C. Jacobs, Z. Islam, R.A.C. Hughes, S. Kusunoki, L. Querol, H.J. Willison, S. Arends, B. van den Berg, A.Y. Doets, S.E. Leonhard, F. Pelouto, J. Roodbol, R.C.M. Thomma, M. van Woerkom, K. Bateman, P.Y.K van den Bergh, E. Dardiotis, T.E. Feasby, S.T. Hsieh, H.C. Lehmann, L. Martín-Aguilar, Q.D. Mohammad, Y. Péréon, S.W. Reddel, R.C. Reisin, P. Ripellino, N. Shahrizaila, Y. Wang, J.M. Addington, S. Ajroud-Driss, G. Antonini, U.A. Badrising, C. Balducci, E. Baroncelli, F.A. Barroso, I.R. Bella, M. Bellucci, L. Benedetti, T.E. Bertorini, R. Bhavaraju-Sanka, T.H. Brannagan, K.M. Brennan, C. Briani, J. Bürmann, M. Busby, S. Butterworth, C. Casasnovas, C. Castellano, G. Cavaletti, C.C. Chao, S. Chen, K.G. Claeys, M.E. Conti, J.S. Cosgrove, C. Cutelle, M.C. Dalakas, M.M. Dimachkie, A. Echaniz-Laguna, F. Eftimov, R. Fazio, J. Fehmi, C. Fokke, T. Fujioka, E.A. Fulgenzi, G. Galassi, T. García-Sobrino, M.P.J. Garssen, P.N. Gengadharan, C.J. Gijsbers, J.M. Gilchrist, H.J. Gilhuis, J.M. Goldstein, N.A. Goyal, A. Grapperon, V. Granit, Y.A.M. Grimbergen, G. Gutiérrez-Gutiérrez, L. Gutmann, R.D.M. Hadden, J.G.J. Hoeijmakers, J.K.L. Holt, M. Htut, A. Humm, T. Hundsberger, B. Islam, K. Jellema, I. Jericó Pascual, K. Kaida, S. Karafiath, H.D. Katzberg, H. Kerkhoff, M. Khoshnoodi, L. Kiers, N. Kokubun, N.A. Kolb, J.C.H.M. Kramers, K. Kuitwaard, T. Kuntzer, M. Kuwahara, J.Y. Kwan, S.S. Ladha, A.M. Lascano, V. Lawson, M.P.T. Lunn, A. Magot, H. Manji, C. Marchesoni, G.A. Marfia, C. Marogianni, C. Márquez Infante, E. Martinez-Hernandez, G. Mataluni, M.G. Mattiazzi, C.J. McDermott, G.D. Meekins, J.A.L. Miller, M.S. Monges, M. Morales de la Prida, G. Morís de la Tassa, C. Nascimbene, R.J. Nowak, J. Ojeda Ruíz de Luna, M. Osei-Bonsu, J. Pardo, M.T. Pulley, S. Rinaldi, R.C. Roberts, I. Rojas-Marcos, S.A. Rudnicki, G.M. Sachs, J.P.A. Samijn, L. Santoro, O. Scheidegger, A. Schenone, L. Schwindling, M.J. Sedano Tous, K.A. Sheikh, N.J. Silvestri, S.H. Sindrup, C.L. Sommer, Y. Song, B. Stein, A.M. Stino, H. Tankisi, P. Tsouni, P.T. Twydell, P. Van Damme, G.W. van Dijk, A.J. van der Kooi, T. van der Ree, R. van Koningsveld, J.D. Varrato, F.H. Vermeij, J. Verschuuren, L.H. Visser, M. Vytopil, W. Waheed, P.W. Wirtz, Y. Yamagishi, L. Zhang, L. Zhou, S.A. Zivkovic
Institutions: Erasmus MC, Elisabeth-TweeSteden Ziekenhuis, Aix-Marseille Université, Hôpital de la Timone, Johns Hopkins University, Johns Hopkins Medicine, University of Glasgow, Tufts University, Aarhus University Hospital, The University of Sydney, Heinrich Heine University Düsseldorf, Palacký University Olomouc, Chiba University, University of Milan, Albert Schweitzer Ziekenhuis, IJsselland Ziekenhuis
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funder: Prinses Beatrix Spierfonds
OpenAlex ID: W7203869037