• 1 From the Mayo Clinic, Rochester, MN (S.J.P.); Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany (A.B.); Tohoku University Graduate School of Medicine (K.F., I.N.) and Tohoku Medical and Pharmaceutical University (I.N.), Sendai, School of Medicine, Fukushima Medical University, Fukushima City (K.F.), and Southern Tohoku Research Institute for Neuroscience, Koriyama (K.F.) - all in Japan; Research Institute and Hospital, National Cancer Center, Goyang, South Korea (H.J.K.); Johns Hopkins University, Baltimore (M.L.); Massachusetts General Hospital and Harvard Medical School (M.L.) and Alexion Pharmaceuticals (A.P., K.P.F., R.A.) - all in Boston; John Radcliffe Hospital, Oxford, United Kingdom (J.P.); Ondokuz Mayis University, Samsun, Turkey (M.T.); First Pavlov State Medical University of St. Petersburg, St. Petersburg, Russia (N.T.); Kuala Lumpur Hospital, Kuala Lumpur, Malaysia (S.V.); Cheng-Hsin General Hospital and School of Medicine, National Yang Ming University, Taipei, Taiwan (K.-C.W.); and the Mayo Clinic, Scottsdale, AZ (D.M.W.)
N Engl J Med, 2019 08 15;381(7):614-625.
PMID: 31050279 DOI: 10.1056/NEJMoa1900866


BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse.

METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death).

RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group.

CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT number, NCT01892345; EudraCT number, 2013-001150-10.).

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.