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)

Kretschmer JR, Tkachenko D, Kümpfel T, Havla J, Engels D, Paul F, Schindler P, Bellmann-Strobl J, Berthele A, Giglhuber K, Zappe C, Klotz L, Revie L, Dawin E, Senel M, Tumani H, Bergh FT, Warnke C, Kraemer M, Walter A, Bayas A, Zettl UK, Lauenstein AS, Yalachkov Y, Etgen T, Kaste M, Luessi F, Gingele S, Passoke S, Weber MS, Sieb JP, Haarmann A, Oschmann P, Rothhammer V, Geis C, Kowarik MC, Kern P, Grothe M, Stephanik H, Angstwurm K, Hoffmann F, Wallwitz U, Wildemann B, Jarius S, Stellmann JP, Pakeerathan T, Schwake C, Ayzenberg I, Kleiter I, Fischer K, Aktas O, Ringelstein M, Häußler V, Trebst C, Hümmert MW (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 16

Article Number: 1575613

DOI: 10.3389/fimmu.2025.1575613

Abstract

Objective: This 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. Methods: This 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. Results: Of 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). Interpretation: LO-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.

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Klinikum der Universität München Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Technische Universität München (TUM) Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Universität Ulm Germany (DE) Universität Leipzig Germany (DE) Alfried Krupp Krankenhaus Germany (DE) Klinikum Herford Germany (DE) Universität Augsburg Germany (DE) Universität Rostock Germany (DE) HELIOS Kliniken Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Kliniken Südostbayern AG Germany (DE) Nordwest-Krankenhaus Sanderbusch Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Georg-August-Universität Göttingen Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Klinikum Bayreuth Germany (DE) Friedrich-Schiller-Universität Jena Germany (DE) Hertie-Institut für klinische Hirnforschung Germany (DE) Asklepios Kliniken Germany (DE) Universität Greifswald Germany (DE) Otto-von-Guericke-Universität Magdeburg Germany (DE) Universität Regensburg Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Katholisches Klinikum Bochum (St. Josef- und St. Elisabeth-Hospital gGmbH) Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE)

How to cite

APA:

Kretschmer, J.R., Tkachenko, D., Kümpfel, T., Havla, J., Engels, D., Paul, F.,... Hümmert, M.W. (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). Frontiers in Immunology, 16. https://doi.org/10.3389/fimmu.2025.1575613

MLA:

Kretschmer, Julian Reza, et al. "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)." Frontiers in Immunology 16 (2025).

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