Safety and Effectiveness of Eculizumab in Japanese Patients With Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder: Interim Analysis of a Post-marketing Surveillance Study

Objective NA. Background The terminal complement C5 inhibitor eculizumab is approved in Japan for the prevention of aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) relapse and undergoing mandatory post-marketing surveillance (PMS) of real-world use. Design/Methods This PMS interim analysis assessed eculizumab's safety and effectiveness in Japanese patients AQP4+ NMOSD patients from approval (November 2019) to interim data cut-off (1 April 2021). Results At data cut-off, 79 patients treated with eculizumab were registered under PMS. Data were available for 20 patients who provided consent for publication and constituted the safety data set; three patients from the phase 3 PREVENT study were excluded from the effectiveness data set. Two patients discontinued before data cut-off owing to physician or patient decision (one each). In the effectiveness data set, 16/17 (94%) patients were female, mean illness duration was 9.2 years (standard deviation [SD] 7.5 years, range 0.3–23.8 years) and mean age at eculizumab initiation was 48.6 years (SD 11.9 years, range 27–77 years). In the 2 years before eculizumab, 12/17 patients experienced relapse, and 6/17 experienced =2 relapses. Importantly, no relapses were reported in the effectiveness data set (10.7 patient-years [PY] of treatment); this compared favorably with a 0.65/PY relapse rate in the 2 years before treatment (34.0 PY). Three adverse events (malaise, eyelid oedema, erythema) and one serious adverse event (urinary tract infection [UTI]) were observed in three patients in the safety data set: eyelid oedema and erythema (one patient) were deemed treatment-related; malaise and UTI were deemed unrelated to treatment. No meningococcal infections were reported, and the safety results were consistent with those from PREVENT. Conclusions For the first time in a real-world setting, eculizumab was effective in preventing relapses and well tolerated in Japanese patients with AQP4+ NMOSD, consistent with its efficacy and safety profile in the global phase 3 PREVENT study.