Eculizumab monotherapy for NMOSD: Data from PREVENT and its open-label extension
Sean J Pittock, Kazuo Fujihara, Jacqueline Palace, Achim Berthele, Ho Jin Kim, Celia Oreja-Guevara, Ichiro Nakashima, Michael Levy, Shulian Shang, Marcus Yountz, Larisa Miller, Róisín Armstrong, Dean M Wingerchuk, PREVENT Study Group, Sean J Pittock, Kazuo Fujihara, Jacqueline Palace, Achim Berthele, Ho Jin Kim, Celia Oreja-Guevara, Ichiro Nakashima, Michael Levy, Shulian Shang, Marcus Yountz, Larisa Miller, Róisín Armstrong, Dean M Wingerchuk, PREVENT Study Group
Abstract
During PREVENT (a phase 3, randomized, double-blind, placebo-controlled, time-to-event study) and its open-label extension (interim analysis), 33 adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD) received eculizumab monotherapy for a median of 2.8 years (range, 14 weeks-5.2 years). At 192 weeks (~4 years), 96% of these patients were free from adjudicated relapses (Kaplan-Meier analysis; 95% confidence interval, 75.7-99.4). During PREVENT, 95% (20/21) of patients receiving eculizumab monotherapy had no disability worsening. Eculizumab monotherapy provides effective long-term relapse prevention, relieving the chronic immunosuppression burden in patients with AQP4-IgG + NMOSD. ClinicalTrials.gov; PREVENT: NCT01892345; open-label extension: NCT02003144.
Keywords: Clinical trial; neuromyelitis optica (NMO).
Conflict of interest statement
Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.J.P. reports grants, personal fees, and nonfinancial support from Alexion Pharmaceuticals; grants from Autoimmune Encephalitis Alliance and Grifols; grants, personal fees, nonfinancial support, and other support from MedImmune; other support from Astellas; and personal fees from UCB. He has a patent, Patent# 8,889,102 (Application#12-678350, Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia)—issued; a patent, Patent# 9,891,219B2 (Application#12-573942, Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive)—issued; a patent, GFAP-IgG—pending; a patent, Septin-5-IgG—pending; a patent, MAP1B-IgG—pending; and a patent, KLHL11—pending. K.F. reports personal fees and other support from Alexion Pharmaceuticals during the conduct of the study. Outside the submitted work, he has received personal fees and other support from Asahi Kasei Medical, Bayer, Biogen, Chugai Pharma, Eisai, Mitsubishi Tanabe Pharma, Novartis, Ono Pharmaceutical, Sumitomo Dainippon Pharma, Takeda, Teijin Pharma, and Viela Bio (formerly MedImmune); and grants from the Ministry of Education, Science and Technology of Japan and the Ministry of Health, Welfare and Labor of Japan. J.P. is partly funded by highly specialized services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and fees for advisory work from Abide Therapeutics, Alexion Pharmaceuticals, ARGENX, Bayer Schering, Biogen Idec, Chugai Pharma, EuroImmun, Genzyme, MedDay, MedImmune, Merck Serono, Novartis, Roche, Teva, UCB, and Viela Bio; grants from Abide Therapeutics, Alexion Pharmaceuticals, Bayer Schering, Biogen Idec, Chugai Pharma, Genzyme, MedImmune, Merck Serono, Novartis, and Teva; and grants for research studies from Eugène Devic European Network, Grant for Multiple Sclerosis Innovation, Guthy-Jackson Charitable Foundation, John Fell Fund, Medical Research Council, MS Society, Myaware, Oxford Health Services Research Committee, and UK National Institute for Health Research. A.B. reports compensation for clinical trials received by his institution from Alexion Pharmaceuticals, Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva; and personal fees and nonfinancial support from Alexion Pharmaceuticals, Bayer, Biogen, Celgene, Merck Serono, Mylan, Novartis, Roche, and Sanofi Genzyme. H.J.K. has received a grant from the National Research Foundation of Korea; reports consultancy/speaker fees from Alexion Pharmaceuticals, Aprilbio, Celltrion, Eisai, HanAll BioPharma, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and Viela Bio; serves on a steering committee for Viela Bio (formerly MedImmune); and is a co-editor for the Multiple Sclerosis Journal and an associate editor for the Journal of Clinical Neurology. C.O.-G. has received speaker fees from Biogen Idec, Celgene, Genzyme, Novartis, Roche, Sanofi Merck, and Teva. I.N. reports personal fees from Biogen Japan, Mitsubishi Tanabe Pharma, Novartis, and Takeda; and grants from LSI Medience, the Ministry of Education, Science and Technology of Japan, and the Ministry of Health, Welfare and Labor of Japan. M.L. reports research support from Alexion Pharmaceuticals, Alnylam, ApoPharma, Sanofi Genzyme, Takeda (formerly Shire), Viela Bio (formerly MedImmune), and ViroPharma; and serves as a consultant for Alexion Pharmaceuticals, ApoPharma, Chugai Pharma, MedImmune, Quest Diagnostics, Sanofi Genzyme, and Takeda (formerly Shire). S.S., M.Y., and L.M. are employees of and hold stock in Alexion Pharmaceuticals. R.A. was an employee of and holds stock in Alexion Pharmaceuticals. D.M.W. reports grants from Alexion Pharmaceuticals during the conduct of the study; and personal fees from Biogen, Celgene, Genentech, MedImmune, Novartis, Reistone Biopharma, TG Therapeutics, and Third Rock Ventures.
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Source: PubMed