Eculizumab Use in Neuromyelitis Optica Spectrum Disorders
Marius Ringelstein, Susanna Asseyer, Gero Lindenblatt, Katinka Fischer, Refik Pul, Jelena Škuljec, Lisa Revie, Katrin Giglhuber, Vivien Häußler, Michael Karenfort, Kerstin Hellwig, Friedemann Paul, Judith Bellmann–Strobl, Carolin Otto, Klemens Ruprecht, Tjalf Ziemssen, Alexander Emmer, Veit Rothhammer, Florian T. Nickel, Klemens Angstwurm, Ralf A. Linker, Sarah Laurent, Clemens Warnke, Sven Jarius, Mirjam Korporal‐Kuhnke, Brigitte Wildemann, S. Wolff, Maria Seipelt, Yavor Yalachkov, Nele Retzlaff, Uwe K. Zettl, Paulus Rommer, Markus C. Kowarik, Jonathan Wickel, Christian Geis, Martin W. Hümmert, Corinna Trebst, Makbule Şenel, Ralf Gold, Luisa Klotz, Christoph Kleinschnitz, Sven G. Meuth, Orhan Aktaş, Achim Berthele, Ilya Ayzenberg, for the German Neuromyelitis Optica Study Group (NEMOS)
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: < 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.