Authors:
Marius Ringelstein (Düsseldorf | DE)
Susanna Asseyer (Berlin | DE)
Gero Lindenblatt (Neuss | DE)
Katinka Fischer (Düsseldorf | DE)
Refik Pul (Essen | DE)
Sinem-Hilal Özalp (Essen | DE)
Lisa Lohmann (Münster | DE)
Katrin Giglhuber (Munich | DE)
Vivien Häußler (Hamburg | DE)
Michael Karenfort (Düsseldorf | DE)
Kerstin Hellwig (Bochum | DE)
Friedemann Paul (Berlin | DE)
Judith Bellmann-Strobl (Berlin | DE)
Carolin Otto (Berlin | DE)
Klemens Ruprecht (Berlin | DE)
Tjalf Ziemssen (Dresden | DE)
Alexander Emmer (Halle | DE)
Veit Rothhammer (Erlangen | DE)
Florian T. Nickel (Erlangen | DE)
Klemens Angstwurm (Regensburg | DE)
Ralf Linker (Regensburg | DE)
Sarah Laurent (Köln | DE)
Clemens Warnke (Köln | DE)
Sven Jarius (Heidelberg | DE)
Mirjam Korporal-Kuhnke (Heidelberg | DE)
Brigitte Wildemann (Heidelberg | DE)
Stephanie Wolff (Gießen | DE)
Maria Seipelt (Marburg | DE)
Yavor Yalachkov (Frankfurt | DE)
Nele Retzlaff (Rostock | DE)
Uwe K. Zettl (Rostock | DE)
Paulus Rommer (Wien | AT)
Markus C. Kowarik (Tübingen | DE)
Jonathan Wickel (Jena | DE)
Christian Geis (Jena | DE)
Martin W. Hümmert (Hannover | DE)
Corinna Trebst (Hannover | DE)
Makbule Senel (Ulm | DE)
Ralf Gold (Bochum | DE)
Luisa Klotz (Münster | DE)
Christoph Kleinschnitz (Essen | DE)
Sven G. Meuth (Düssedorf | DE)
Orhan Aktas (Düssedorf | DE)
Achim Berthele (München | DE)
Ilya Ayzenberg (Bochum | DE)
Background: Attack prevention is crucial to avoid disability accumulation in neuromyelitis optica spectrum disorders (NMOSD). Eculizumab, an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial in aquaporin-4 (AQP4)-IgG seropositive (+) NMOSD, but real-world data are only emerging.
Aims: To evaluate the effectiveness and safety of Eculizumab in a real-world setting in Germany and Austria.
Methods: Annualized attack rate (AAR), expanded disability status scale (EDSS), magnetic resonance imaging (MRI), adverse events including mortality, and tolerability of meningococcal vaccinations were retrospectively evaluated in patients with AQP4-IgG+ NMOSD (n=52), MOG-IgG-associated disease (MOGAD, n=2), and double-seronegative NMOSD (n=1) treated with Eculizumab between December 2014 and April 2022.
Results: Fifty-five patients (84% females, age 55.1±15.8 years) received Eculizumab for 14.7 (IQR 8.1-21.3) months. Fourty patients (73%) received meningococcal vaccination before starting Eculizumab, nine with concomitant oral prednisone and 31 without. Ten of the latter (32%) experienced attacks shortly after vaccination (9.6±8.6 days). In contrast, no post-vaccinal attack occurred in the nine patients vaccinated while on oral prednisone as well as in 22 patients who were (re-)vaccinated while on Eculizumab. During Eculizumab therapy, 87% of patients were attack-free. The median AAR decreased from 1.0 (range 0-4) in the two years preceding Eculizumab to 0 (range 0-1.4; p < 0.001). Add-on immunosuppressants in 13/55 (24%) patients showed no advantage in AAR compared to Eculizumab monotherapy. EDSS from start to last follow-up during Eculizumab treatment was stable (median 6.0), and the proportion of patients with new T2- or gadolinium-enhancing MRI-lesions in the brain and spinal cord decreased. Seven (13%) patients experienced serious infections. Five patients (9%; median age 53.7 years) died on Eculizumab treatment: one from myocardial infarction, one from ileus with secondary sepsis and three in the context of systemic infections, including one from meningococcal sepsis. The discontinuation rate overall was 20%.
Conclusions: Eculizumab proved to be highly effective in preventing NMOSD attacks. An increased risk of attacks following meningococcal vaccination prior to treatment start and potentially fatal systemic infections during Eculizumab must be considered. Further research is necessary to explore the