Frontiers in Immunology (Apr 2025)
Worse recovery from acute attacks and faster disability accumulation highlights the unmet need for improved treatment in patients with late-onset neuromyelitis optica spectrum disorders (COPTER-LO study)
- Julian Reza Kretschmer,
- Daria Tkachenko,
- Tania Kümpfel,
- Joachim Havla,
- Daniel Engels,
- Friedemann Paul,
- Friedemann Paul,
- Patrick Schindler,
- Patrick Schindler,
- Judith Bellmann-Strobl,
- Judith Bellmann-Strobl,
- Achim Berthele,
- Katrin Giglhuber,
- Clarissa Zappe,
- Luisa Klotz,
- Lisa Revie,
- Eva Dawin,
- Makbule Senel,
- Hayrettin Tumani,
- Florian Then Bergh,
- Clemens Warnke,
- Markus Kraemer,
- Markus Kraemer,
- Annette Walter,
- Antonios Bayas,
- Uwe K. Zettl,
- Ann-Sophie Lauenstein,
- Yavor Yalachkov,
- Thorleif Etgen,
- Matthias Kaste,
- Felix Luessi,
- Stefan Gingele,
- Sarah Passoke,
- Martin S. Weber,
- Jörn Peter Sieb,
- Axel Haarmann,
- Patrick Oschmann,
- Veit Rothhammer,
- Christian Geis,
- Markus C. Kowarik,
- Peter Kern,
- Matthias Grothe,
- Heike Stephanik,
- Klemens Angstwurm,
- Frank Hoffmann,
- Ulrike Wallwitz,
- Brigitte Wildemann,
- Sven Jarius,
- Jan-Patrick Stellmann,
- Jan-Patrick Stellmann,
- Jan-Patrick Stellmann,
- Thivya Pakeerathan,
- Carolin Schwake,
- Ilya Ayzenberg,
- Ingo Kleiter,
- Ingo Kleiter,
- Katinka Fischer,
- Orhan Aktas,
- Marius Ringelstein,
- Marius Ringelstein,
- Vivien Häußler,
- Corinna Trebst,
- Martin W. Hümmert
Affiliations
- Julian Reza Kretschmer
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Daria Tkachenko
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Tania Kümpfel
- Institute of Clinical Neuroimmunology, LMU University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
- Joachim Havla
- Institute of Clinical Neuroimmunology, LMU University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
- Daniel Engels
- Institute of Clinical Neuroimmunology, LMU University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany
- Friedemann Paul
- Department of Neurology, Charite Universitätsmedizin Berlin, Berlin, Germany
- Friedemann Paul
- Charité Universitätsmedizin Berlin, Experimental and Clinical Research Center and Max Delbrueck Center for Molecular Medicine, Berlin, Germany
- Patrick Schindler
- Department of Neurology, Charite Universitätsmedizin Berlin, Berlin, Germany
- Patrick Schindler
- Charité Universitätsmedizin Berlin, Experimental and Clinical Research Center and Max Delbrueck Center for Molecular Medicine, Berlin, Germany
- Judith Bellmann-Strobl
- Department of Neurology, Charite Universitätsmedizin Berlin, Berlin, Germany
- Judith Bellmann-Strobl
- Charité Universitätsmedizin Berlin, Experimental and Clinical Research Center and Max Delbrueck Center for Molecular Medicine, Berlin, Germany
- Achim Berthele
- Department of Neurology, Technical University Munich, Munich, Germany
- Katrin Giglhuber
- Department of Neurology, Technical University Munich, Munich, Germany
- Clarissa Zappe
- Department of Neurology, Technical University Munich, Munich, Germany
- Luisa Klotz
- Department of Neurology, University of Münster, Münster, Germany
- Lisa Revie
- Department of Neurology, University of Münster, Münster, Germany
- Eva Dawin
- Department of Neurology, University of Münster, Münster, Germany
- Makbule Senel
- Department of Neurology, University of Ulm, Ulm, Germany
- Hayrettin Tumani
- Department of Neurology, University of Ulm, Ulm, Germany
- Florian Then Bergh
- Department of Neurology, University of Leipzig, Leipzig, Germany
- Clemens Warnke
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Markus Kraemer
- 0Department of Neurology, Alfried Krupp Hospital Essen, Essen, Germany
- Markus Kraemer
- 7Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Annette Walter
- 1Department of Neurology, Herford Hospital, Herford, Germany
- Antonios Bayas
- 2Department of Neurology, Medical Faculty, University of Augsburg, Augsburg, Germany
- Uwe K. Zettl
- 3Department of Neurology, University of Rostock, Rostock, Germany
- Ann-Sophie Lauenstein
- 4Department of Neurology, DKD Helios Hospital Wiesbaden, Wiesbaden, Germany
- Yavor Yalachkov
- 5Department of Neurology, Goethe-University Frankfurt, University Medicine, Frankfurt am Main, Germany
- Thorleif Etgen
- 6Department of Neurology, Klinikum Traunstein, Traunstein, Germany
- Matthias Kaste
- 7Department of Neurology, Nordwest-Krankenhaus Sanderbusch, Sanderbusch, Germany
- Felix Luessi
- 8Department of Neurology, University of Mainz, Mainz, Germany
- Stefan Gingele
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Sarah Passoke
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Martin S. Weber
- 9Department of Neurology, University of Göttingen, Göttingen, Germany
- Jörn Peter Sieb
- 0Department of Neurology, Helios Hanseklinikum Stralsund, Stralsund, Germany
- Axel Haarmann
- 1Department of Neurology, University of Würzburg, Würzburg, Germany
- Patrick Oschmann
- 2Department of Neurology, Klinikum Bayreuth, Bayreuth, Germany
- Veit Rothhammer
- 3Department of Neurology, FAU Erlangen-Nuremberg, Erlangen, Germany
- Christian Geis
- 4Department of Neurology, University of Jena, Jena, Germany
- Markus C. Kowarik
- 5Department of Neurology & Stroke and Hertie-Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, Tübingen, Germany
- Peter Kern
- 6Department of Neurology, Asklepios Expert Clinic Teupitz, Teupitz, Germany
- Matthias Grothe
- 7Department of Neurology, University of Greifswald, Greifswald, Germany
- Heike Stephanik
- 8Department of Neurology, University of Magdeburg, Magdeburg, Germany
- Klemens Angstwurm
- 9Department of Neurology, University of Regensburg, Regensburg, Germany
- Frank Hoffmann
- 0Department of Neurology, Hospital Martha-Maria, Halle, Germany
- Ulrike Wallwitz
- 0Department of Neurology, Hospital Martha-Maria, Halle, Germany
- Brigitte Wildemann
- 1Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany
- Sven Jarius
- 1Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany
- Jan-Patrick Stellmann
- 2Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany
- Jan-Patrick Stellmann
- 3CEMEREM, APHM, Hôspital de la Timone, Marseille, France
- Jan-Patrick Stellmann
- 4CRMBM, Aix Marseille Univ, CNRS, Marseille, France
- Thivya Pakeerathan
- 5Department of Neurology, St.Josef Hospital, Ruhr University Bochum, Bochum, Germany
- Carolin Schwake
- 5Department of Neurology, St.Josef Hospital, Ruhr University Bochum, Bochum, Germany
- Ilya Ayzenberg
- 5Department of Neurology, St.Josef Hospital, Ruhr University Bochum, Bochum, Germany
- Ingo Kleiter
- 5Department of Neurology, St.Josef Hospital, Ruhr University Bochum, Bochum, Germany
- Ingo Kleiter
- 6Marianne-Strauss-Klinik, Behandlungszentrum für Multiple Sklerose Kranke, Berg, Germany
- Katinka Fischer
- 7Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Orhan Aktas
- 1Department of Neurology, Herford Hospital, Herford, Germany
- Marius Ringelstein
- 1Department of Neurology, Herford Hospital, Herford, Germany
- Marius Ringelstein
- 8Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Vivien Häußler
- 2Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany
- Corinna Trebst
- Department of Neurology, Hannover Medical School, Hannover, Germany
- Martin W. Hümmert
- Department of Neurology, Hannover Medical School, Hannover, Germany
- DOI
- https://doi.org/10.3389/fimmu.2025.1575613
- Journal volume & issue
-
Vol. 16
Abstract
ObjectiveThis study analyzed clinical characteristics, attack recovery and long-term disability accumulation in late-onset (LO ≥ 50 years at onset) versus early-onset (EO < 50 years) NMOSD.MethodsThis multicenter cohort study included demographic and clinical data from 446 NMOSD patients collected from 35 German Neuromyelitis Optica Study Group (NEMOS) centers. Time to disability milestones was estimated through Kaplan-Meier analysis and Cox proportional hazard regression models adjusted for sex, year of onset, immunotherapy exposure and antibody status. Generalized estimating equations (GEE) were used to compare attack outcomes.ResultsOf the 446 NMOSD patients analyzed (83.4% female, 85.4% AQP4-IgG-positive, median age at disease onset = 43 years), 153 had a late-onset (34.3%). AQP4-IgG+ prevalence was higher in LO- than in EO-NMOSD (94.1% vs. 80.9%, p<0.001). Optic neuritis at onset was more frequent in EO-NMOSD (27.4% vs. 42.6%, p<0.002), whereas myelitis was more common in LO-NMOSD (58.4% vs. 37.9%, p<0.001). Both groups had similar annualized attack rates (AAR, 0.51 vs. 0.54, p=0.352), but attack recovery was poorer (complete remission in 15.6% vs. 27.4%, p<0.001) and relapse-associated worsening (RAW) was higher in LO-NMOSD (RAW: 3 vs. 0.5, p<0.001). Long-term immunotherapy use was comparable. LO-NMOSD exhibited faster progression to disability endpoints (EDSS 4: HR = 2.64, 95% CI=1.81–3.84).InterpretationLO-NMOSD patients presented more often with myelitis, experienced worse attack outcomes and faster disability accumulation, despite comparable AAR, acute attack treatment and long-term treatment regimens. Accordingly, therapeutic strategies for attack and prophylactic treatment in LO-NMOSD have to be improved.
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