-
Tytuł:
-
Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial.
-
Autorzy:
-
Palace J; Nuffield Department of Clinical Neurosciences, West Wing, John Radcliffe Hospital, University of Oxford, Headley Way, Oxford, OX3 9DU, UK. Electronic address: .
Wingerchuk DM; Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. Electronic address: .
Fujihara K; Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, 980-8574, Japan; Department of Multiple Sclerosis Therapeutics, Fukushima Medical University, Fukushima City, 960-1295, Japan; Multiple Sclerosis and Neuromyelitis Optica Center, Southern TOHOKU Research Institute for Neuroscience (STRINS), Koriyama, 963-8563, Japan. Electronic address: .
Berthele A; Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Neuro-Kopf-Zentrum, Ismaninger Str. 22, 81675 Munich, Germany. Electronic address: .
Oreja-Guevara C; Hospital Universitario Clínico San Carlos, Calle del Profesor Martín Lagos, 28040 Madrid; Departamento de Medicina, Universidad Complutense de Madrid (UCM); IdISSC, 28040 Madrid, Spain. Electronic address: .
Kim HJ; Department of Neurology, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, South Korea. Electronic address: .
Nakashima I; Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, 980-8574, Japan; Division of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan. Electronic address: .
Levy M; Department of Neurology, Johns Hopkins University, 1800 Orleans Street, Baltimore, MD 21287, USA. Electronic address: .
Terzi M; Department of Neurology, Ondokuz Mayıs University, Samsun, Turkey. Electronic address: .
Totolyan N; Department of Neurology, First Pavlov State Medical University of St Petersburg, 6/8, Lva Tolstogo str., 197022, St Petersburg, Russia. Electronic address: .
Viswanathan S; Department of Neurology, Kuala Lumpur Hospital, Jalan Pahang, Kuala Lumpur, 50560, Malaysia. Electronic address: .
Wang KC; Cheng-Hsin General Hospital, 45 Zhenxing Street, Beitou District, Taipei, Taiwan 112; School of Medicine, National Yang Ming University, 155, Section 2, Linong St, Beitou District, Taipei C, Taiwan 112. Electronic address: .
Pace A; Alexion Pharmaceuticals, Boston, 121 Seaport Boulevard, Boston, MA 02210, USA. Electronic address: .
Yountz M; Alexion Pharmaceuticals, Boston, 121 Seaport Boulevard, Boston, MA 02210, USA. Electronic address: .
Miller L; Alexion Pharmaceuticals, Boston, 121 Seaport Boulevard, Boston, MA 02210, USA. Electronic address: .
Armstrong R; Alexion Pharmaceuticals, Boston, 121 Seaport Boulevard, Boston, MA 02210, USA. Electronic address: .
Pittock S; Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address: .
-
Corporate Authors:
-
PREVENT Study Group
-
Źródło:
-
Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2021 Jan; Vol. 47, pp. 102641. Date of Electronic Publication: 2020 Nov 26.
-
Typ publikacji:
-
Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial
-
Język:
-
English
-
Imprint Name(s):
-
Original Publication: [Amsterdam] : Elsevier B. V.
-
MeSH Terms:
-
Neuromyelitis Optica*/drug therapy
Adult ; Antibodies, Monoclonal, Humanized/therapeutic use ; Aquaporin 4 ; Humans ; Rituximab/therapeutic use
-
Contributed Indexing:
-
Keywords: Aquaporin-4 immunoglobulin G-positive; Eculizumab; Neuromyelitis optica spectrum disorder; Relapse; Safety; Subgroups
-
Molecular Sequence:
-
ClinicalTrials.gov NCT01892345
-
Substance Nomenclature:
-
0 (Antibodies, Monoclonal, Humanized)
0 (Aquaporin 4)
4F4X42SYQ6 (Rituximab)
A3ULP0F556 (eculizumab)
-
Entry Date(s):
-
Date Created: 20201214 Date Completed: 20210514 Latest Revision: 20210514
-
Update Code:
-
20240104
-
DOI:
-
10.1016/j.msard.2020.102641
-
PMID:
-
33310418
-
Background: Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT.
Methods: In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity.
Results: The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder.
Conclusion: Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate.
Trial Registration: NCT01892345 (ClinicalTrials.gov).
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
