Eculizumab Use in Neuromyelitis Optica Spectrum Disorders

Ringelstein, Marius and Asseyer, Susanna and Lindenblatt, Gero and Fischer, Katinka and Pul, Refik and Skuljec, Jelena and Revie, Lisa and Giglhuber, Katrin and Haeussler, Vivien and Karenfort, Michael and Hellwig, Kerstin and Paul, Friedemann and Bellmann-Strobl, Judith and Otto, Carolin and Ruprecht, Klemens and Ziemssen, Tjalf and Emmer, Alexander and Rothhammer, Veit and Nickel, Florian T. and Angstwurm, Klemens and Linker, Ralf and Laurent, Sarah A. and Warnke, Clemens and Jarius, Sven and Korporal-Kuhnke, Mirjam and Wildemann, Brigitte and Wolff, Stephanie and Seipelt, Maria and Yalachkov, Yavor and Retzlaff, Nele and Zettl, Uwe K. and Rommer, Paulus S. and Kowarik, Markus C. and Wickel, Jonathan and Geis, Christian and Huemmert, Martin W. and Trebst, Corinna and Senel, Makbule and Gold, Ralf and Klotz, Luisa and Kleinschnitz, Christoph and Meuth, Sven G. and Aktas, Orhan and Berthele, Achim and Ayzenberg, Ilya (2024) Eculizumab Use in Neuromyelitis Optica Spectrum Disorders. NEUROLOGY, 103 (9): e209888. ISSN 0028-3878, 1526-632X

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Abstract

Background and Objectives Attack prevention is crucial in managing neuromyelitis optica spectrum disorders (NMOSDs). Eculizumab (ECU), an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial of aquaporin-4 (AQP4)-IgG seropositive(+) NMOSDs. In this article, we evaluated effectiveness and safety of ECU in routine clinical care. Methods We retrospectively evaluated patients with AQP4-IgG+ NMOSD treated with ECU between December 2014 and April 2022 at 20 German and 1 Austrian university center(s) of the Neuromyelitis Optica Study Group (NEMOS) by chart review. Primary outcomes were effectiveness (assessed using annualized attack rate [AAR], MRI activity, and disability changes [Expanded Disability Status Scale {EDSS}]) and safety (including adverse events, mortality, and attacks after meningococcal vaccinations), analyzed by descriptive statistics. Results Fifty-two patients (87% female, age 55.0 +/- 16.3 years) received ECU for 16.2 (interquartile range [IQR] 9.6 - 21.7) months. Forty-five patients (87%) received meningococcal vaccination before starting ECU, 9 with concomitant oral prednisone and 36 without. Seven of the latter (19%) experienced attacks shortly after vaccination (median: 9 days, IQR 6-10 days). No postvaccinal attack occurred in the 9 patients vaccinated while on oral prednisone before starting ECU and in 25 (re-)vaccinated while on ECU. During ECU therapy, 88% of patients were attack-free. The median AAR decreased from 1.0 (range 0-4) in the 2 years preceding ECU to 0 (range 0-0.8; p < 0.001). The EDSS score from start to the last follow-up was stable (median 6.0), and the proportion of patients with new T2-enhancing or gadolinium-enhancing MRI lesions in the brain and spinal cord decreased. Seven patients (13%) experienced serious infections. Five patients (10%; median age 53.7 years) died on ECU treatment (1 from myocardial infarction, 1 from ileus with secondary sepsis, and 3 from systemic infection, including 1 meningococcal sepsis), 4 were older than 60 years and severely disabled at ECU treatment start (EDSS score >= 7). The overall discontinuation rate was 19%. Discussion Eculizumab proved to be effective in preventing NMOSD attacks. An increased risk of attacks after meningococcal vaccination before ECU start and potentially fatal systemic infections during ECU-particularly in patients with comorbidities-must be considered. Further research is necessary to explore optimal timing for meningococcal vaccinations. Classification of Evidence This study provides Class IV evidence that eculizumab reduces annualized attack rates and new MRI lesions in AQP4-IgG+ patients with NMOSD.

Item Type:	Article
Uncontrolled Keywords:	DOUBLE-BLIND; MENINGOCOCCAL DISEASE; EFFICACY; SAFETY; SATRALIZUMAB; MULTICENTER; THERAPY; PHASE-3;
Subjects:	600 Technology > 610 Medical sciences Medicine
Divisions:	Medicine > Lehrstuhl für Neurologie
Depositing User:	Dr. Gernot Deinzer
Date Deposited:	23 Jul 2025 09:45
Last Modified:	23 Jul 2025 09:45
URI:	https://pred.uni-regensburg.de/id/eprint/65750

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