Long-Term Efficacy and Safety of Eculizumab in AQP4+ Neuromyelitis Optica Spectrum Disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) relapses can cause significant and irreversible neurologic disability. In PREVENT, eculizumab reduced the risk of relapse in patients with aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD by 94.2% vs placebo (hazard ratio 0.058; 95% confidence interval [CI]: 0.017–0.197; p < 0.0001) and adjudicated annualized relapse rate (ARR) for eculizumab was 0.02. The rate of adverse events (AEs)/100 patient-years (PY) was 749.3 for eculizumab and 1160.9 for placebo. Objectives: To present the long-term efficacy and safety of eculizumab in patients with AQP4+ NMOSD during PREVENT (NCT01892345) and its ongoing open-label extension (OLE; NCT02003144). Methods: During PREVENT, adults with AQP4+ NMOSD received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo with/without concomitant immunosuppressive therapy (IST). Patients who completed PREVENT could enroll in the OLE to receive eculizumab. Eculizumab safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. Results: Overall, 137 patients received eculizumab, and were observed for a median (range) of 133.29 (5.1 – 276.9) weeks, for a combined total of 362.3 PY. The estimated percentage of patients who were relapse free at 192 weeks (3.7 years) was 94.4% (95% CI: 88.6 –97.3).The adjudicated ARR was 0.025 (95% CI: 0.013–0.048) and the annualized relapse-related hospitalization rate (ARRHR) was 0.03/PY (95% CI: 0.017–0.055). Rates of AEs and serious AEs (SAEs)/100 PY were 732.5 and 33.7, respectively. Common AEs included headache (29.2%) and upper respiratory tract infection (27.7%). Common SAEs, excluding NMOSD relapses, were pneumonia (3.6%), urinary tract infection (2.9%) and acute cholecystitis (2.9%). One patient died during PREVENT (pulmonary empyema) and one patient developed a disseminated Neisseria gonorrhoeae infection. In all, 25/137 patients (18.2%) developed a serious infection vs 6/47 (12.8%) receiving placebo in PREVENT. No patient had a meningococcal infection. During the OLE, 50/119 patients (42%) changed concomitant IST; most patients (44/50) stopped or decreased concomitant IST dose. Conclusions: During PREVENT and its OLE, the percentage of relapse-free patients remained high (94%) through 192 weeks. Eculizumab was well tolerated and AEs were consistent with the safety profile established in other indications. ARRHR was low and many patients were able to reduce or stop concomitant IST.

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