Early Treatment With Intravenous Immunoglobulins and Outcomes of Patients With Anti-IgLON5 Disease
Thomas Grüter, Carles Gaig, Yvette S. Crijnen, Maarten J. Titulaer, Lídia Sabater, Anna Heidbreder, Justina Dargvainiene, Anja Tietz, Stjepana Kovac, Andre Dik, María Elena Erro, Jan Lewerenz, Andrea Kraft, Frank Seifert, Romana Höftberger, Franziska Thaler, Lucie de Azevedo, Jonathan Wickel, Juna M. de Vries, Agnita J.W. Boon, Robin W. van Steenhoven, Ralf Gold, Klaus-Peter Wandinger, Gregor Kuhlenbäumer, Josep Dalmau, Frank Leypoldt, Francesc Graus, Ilya Ayzenberg, Anti-IgLON5 Disease Study Group, Gian Maria Asioli, Michael Adelmann, Luise Appeltshauser, Carolin Baade‐Büttner, Andreas van Baalen, Sebastian Baatz, Oliver Bähr, Bettina Balint, Sebastian Bauer, Annette Baumgärtner, Tobias Baumgartner, Antonios Bayas, Stefanie Becker, Sonka Benesch, Robert L. Berger, Birgit Berger, Martin Berghoff, Sascha Berning, Sarah Bernsen, Achim Berthele, Christian G. Bien, Corinna Bien, Julia Bierwith, Andreas Binder, Stefan Bittner, Daniel Bittner, Morten Blaabjerg, Franz Blaes, Astrid Blaschek, Amelie Bohn, Marie Braun, Norbert Brüggemann, Sergio Castro‐Gomez, Timo Deba, Julia Maren Decker, Johanna-Maria Dietmaier, Julian Dominik, Kathrin Doppler, Mona Dreesmann, Friedrich Ebinger, Lena Edelhoff, Laura Ehrhardt, Sven Ehrlich, Thilo van Eimeren, Katharina Eisenhut, Alexander Emmer, Dominique Endres, Marina Entscheva, Daniela Esser, Thorleif Etgen, Jürgen Faiss, Kim Kristin Falk, Tarsis Farias, Walid Fazeli, Alexander Finke, Carsten Finke, Felix Fischbach, Dirk Fitzner, Marina Flotats‐Bastardas, Mathias Fousse, Suzanne C. Franken, Tobias Freilinger, Paul Friedemann, Manuel A. Friese, Marco Gallus, Juan Carlos García‐Moncó, M. M. Gebhard, Christian Geis, Caroline Giordana, Anna Gorsler, Armin Grau
Abstract
Importance: Anti-IgLON5 disease is an autoimmune encephalopathy that often leads to severe disability or death. The efficacy of immunotherapy remains unknown. Objective: To investigate whether early immunotherapy is associated with disability and death in anti-IgLON5 disease. Design, Setting, and Participants: This retrospective, multicenter cohort study of patients with anti-IgLON5 disease was conducted from 2014 to 2024, with a median (IQR) follow-up of 66 (33-97) months after disease onset. Data from the German Network for Research on Autoimmune Encephalitis Registry, University Hospital Clinic of Barcelona (Spain), and Erasmus University Medical Center (the Netherlands) were analyzed. Eligibility criteria were clinical features consistent with anti-IgLON5 disease and the presence of IgLON5 antibodies in serum or cerebrospinal fluid. Data were collected by treating physicians using a structured questionnaire. Of 121 patients systematically selected from participating centers and registries, 14 patients were excluded due to insufficient clinical information or withdrawal of consent. Intervention: Initiation of immunotherapy based on the treating physician's decision. Main Outcomes and Measures: Clinical disability was assessed using the modified Rankin Scale (mRS) at the most recent follow-up visit and the proportion of patients who died. Results: Among 107 patients with anti-IgLON5 disease (46 female [43.0%] and 61 male [57.0%]; median [IQR] age at the time of disease onset, 64 [57-70] years), 25 patients (23.4%) received immunotherapy during the first year of disease onset and 57 patients (53.3%) received it later. Among early treated patients, 9 individuals (36.0%) received intravenous immunoglobulins and 13 individuals (52.0%) received rituximab. A total of 44 patients (41.1%) died, and at least two-thirds of these deaths were related to anti-IgLON5 disease (28 patients [63.6%]). Early immunotherapy was the only modifiable independent factor associated with a lower long-term disability (odds ratio, 0.32; 95% CI, 0.13-0.83; P = .02) and survival (odds ratio, 2.70; 95% CI, 0.99-7.69; P = .047). Only intravenous immunoglobulin started within the first year of disease onset was associated with a lower median (IQR) mRS score at the most recent follow-up (2 [1-2.5] vs 3 [2-6]; P = .005; r = 0.55) and a lower proportion of deaths (0 of 9 patients vs 6 of 16 patients [37.5%]; P = .04) compared with other early immunotherapies despite a similar baseline mRS score. Conclusions and Relevance: In this study, early initiation of intravenous immunoglobulins (within the first year of onset) was associated with favorable long-term outcomes and improved survival in anti-IgLON5 disease. Larger prospective studies are needed to validate this finding.