TY - JOUR
T1 - Eculizumab in Asian patients with anti-aquaporin-IgG-positive neuromyelitis optica spectrum disorder
T2 - A subgroup analysis from the randomized phase 3 PREVENT trial and its open-label extension
AU - on behalf of the PREVENT Study Group
AU - Kim, Ho Jin
AU - Nakashima, Ichiro
AU - Viswanathan, Shanthi
AU - Wang, Kai Chen
AU - Shang, Shulian
AU - Miller, Larisa
AU - Yountz, Marcus
AU - Wingerchuk, Dean M.
AU - Pittock, Sean J.
AU - Levy, Michael
AU - Berthele, Achim
AU - Totolyan, Natalia
AU - Palace, Jacqueline
AU - Barnett, Michael H.
AU - Fujihara, Kazuo
N1 - Funding Information:
This work was supported by Alexion Pharmaceuticals.
Funding Information:
This work was funded by Alexion Pharmaceuticals. Ho Jin Kim has received a grant from the National Research Foundation of Korea; reports consultancy/speaker fees from Alexion Pharmaceuticals, Aprilbio, Celltrion, Eisai, HanAll Biopharma, MDimune, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and Viela Bio (formerly MedImmune); 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. Ichiro Nakashima 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. Shanthi Viswanathan and Kai-Chen Wang report no disclosures. Shulian Shang, Larisa Miller, and Marcus Yountz are employees of and hold stock in Alexion Pharmaceuticals. Dean M. Wingerchuk 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. Sean J. Pittock reports grants, personal fees, and non-financial support from Alexion Pharmaceuticals; grants from Autoimmune Encephalitis Alliance, and Grifols; grants, personal fees, non-financial 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. Michael Levy 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). Achim Berthele 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 non-financial support from Alexion Pharmaceuticals, Bayer, Biogen, Celgene, Merck Serono, Mylan, Novartis, Roche, and Sanofi Genzyme. Natalia Totolyan reports personal fees from Bayer, Janssen, Merck, Receptos, Roche, Sanofi Genzyme, and Teva; grants and personal fees from Actelion, BIOCAD (Russia), and Novartis; and grants from GeNeuro. Jacqueline Palace 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 (formerly MedImmune); grants from Abide Therapeutics, Alexion Pharmaceuticals, Bayer Schering, Biogen Idec, Chugai Pharma, Genzyme, MedImmune, Merck Serono, Novartis, and Teva; and grants from Amplo Biotechnology, Eugène Devic European Network, the Grant for Multiple Sclerosis Innovation, the Guthy-Jackson Charitable Foundation, the John Fell Fund, the Medical Research Council, the MS Society, Myaware, the UK National Institute for Health Research, and Oxford Health Services Research Committee for research studies. Michael H. Barnett reports institutional support for research, speaking and/or participation in advisory boards for Biogen, Merck, Novartis, Roche, and Sanofi Genzyme; and serves as consulting neurologist for RxMx and research director for the Sydney Neuroimaging Analysis Centre. Kazuo Fujihara (senior) 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 Abbvie, Asahi Kasei Medical, Biogen, Chugai, Eisai, Merck Biopharma, Mitsubishi Tanabe, Novartis, Ono, Roche, Sumitomo Dainippon, Takeda, Teijin Pharma, UCB, 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.
Publisher Copyright:
© 2021
PY - 2021/5
Y1 - 2021/5
N2 - Background Eculizumab, a terminal complement inhibitor, significantly reduced the risk of relapse compared with placebo in patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in the PREVENT trial. We report efficacy and safety analyses in Asian patients in PREVENT and its open-label extension (OLE). Methods PREVENT was a double-blind, randomized, phase 3 trial. Patients with AQP4+ NMOSD were randomly assigned (2:1) to receive intravenous eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Patients who completed PREVENT could receive eculizumab in an OLE. Analyses were performed in a prespecified subgroup of Asian patients. Results Of 143 patients enrolled, 52 (36.4%) were included in the Asian subgroup (eculizumab, n = 37; placebo, n = 15); 45 Asian patients received eculizumab in the OLE. Most Asian patients (86.5%) received concomitant immunosuppressive therapy. During PREVENT, one adjudicated relapse occurred in patients receiving eculizumab and six occurred in patients receiving placebo in the Asian subgroup (hazard ratio, 0.05; 95% confidence interval: 0.01–0.35; p = 0.0002). An estimated 95.2% of Asian patients remained relapse-free after 144 weeks of eculizumab treatment. Upper respiratory tract infections, headache, and nasopharyngitis were the most common adverse events with eculizumab in the Asian subgroup. Conclusion Eculizumab reduces the risk of relapse in Asian patients with AQP4+ NMOSD, with a benefit–risk profile similar to the overall PREVENT population. The benefits of eculizumab were maintained during long-term therapy. Clinical trial registration ClinicalTrials.gov identifiers: NCT01892345 (PREVENT); NCT02003144 (open-label extension).
AB - Background Eculizumab, a terminal complement inhibitor, significantly reduced the risk of relapse compared with placebo in patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in the PREVENT trial. We report efficacy and safety analyses in Asian patients in PREVENT and its open-label extension (OLE). Methods PREVENT was a double-blind, randomized, phase 3 trial. Patients with AQP4+ NMOSD were randomly assigned (2:1) to receive intravenous eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Patients who completed PREVENT could receive eculizumab in an OLE. Analyses were performed in a prespecified subgroup of Asian patients. Results Of 143 patients enrolled, 52 (36.4%) were included in the Asian subgroup (eculizumab, n = 37; placebo, n = 15); 45 Asian patients received eculizumab in the OLE. Most Asian patients (86.5%) received concomitant immunosuppressive therapy. During PREVENT, one adjudicated relapse occurred in patients receiving eculizumab and six occurred in patients receiving placebo in the Asian subgroup (hazard ratio, 0.05; 95% confidence interval: 0.01–0.35; p = 0.0002). An estimated 95.2% of Asian patients remained relapse-free after 144 weeks of eculizumab treatment. Upper respiratory tract infections, headache, and nasopharyngitis were the most common adverse events with eculizumab in the Asian subgroup. Conclusion Eculizumab reduces the risk of relapse in Asian patients with AQP4+ NMOSD, with a benefit–risk profile similar to the overall PREVENT population. The benefits of eculizumab were maintained during long-term therapy. Clinical trial registration ClinicalTrials.gov identifiers: NCT01892345 (PREVENT); NCT02003144 (open-label extension).
KW - Anti-aquaporin-4-positive
KW - Asian
KW - Eculizumab
KW - Neuromyelitis optica spectrum disorder
KW - Relapse
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=85101822241&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101822241&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2021.102849
DO - 10.1016/j.msard.2021.102849
M3 - Article
C2 - 33676197
AN - SCOPUS:85101822241
VL - 50
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
M1 - 102849
ER -