Abstract: P604

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

H.J. Kim¹, S.J. Pittock², A. Berthele³, K. Fujihara^4,5,6, M. Levy^7,8, J. Palace⁹, I. Nakashima^4,10, M. Terzi¹¹, N. Totolyan¹², S. Viswanathan¹³, K.-C. Wang^14,15, A. Pace¹⁶, K.P. Fujita¹⁶, M. Yountz¹⁶, R. Armstrong¹⁶, D.M. Wingerchuk¹⁷, The PREVENT study group

¹Neurology, National Cancer Center, Goyang, Republic of Korea, ²Department of Neurology, Mayo Clinic, Rochester, MN, United States, ³Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ⁴Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, ⁵Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine, Fukushima City, ⁶MS & NMO Center, Southern TOHOKU Research Institute for Neuroscience (STRINS), Koriyama, Japan, ⁷Department of Neurology, John Hopkins University, Baltimore, MD, ⁸Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, ⁹Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom, ¹⁰Department of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan, ¹¹Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey, ¹²Department of Neurology, First St Petersburg State Medical University n.a. I.P. Pavlov, St. Petersburg, Russian Federation, ¹³Department of Neurology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia, ¹⁴Cheng-Hsin General Hospital, ¹⁵School of Medicine, National Yang Ming University, Taipei, Taiwan, ¹⁶Alexion Pharmaceuticals, Boston, MA, ¹⁷Department of Neurology, Mayo Clinic, Scottsdale, AZ, United States

Introduction: Relapses resulting in hospitalization are common in patients with the rare autoimmune inflammatory disease neuromyelitis optica spectrum disorder (NMOSD). The randomized, double-blind, placebo-controlled PREVENT study assessed the safety and efficacy of eculizumab in aquaporin-4 immunoglobulin G (AQP4-IgG)-positive NMOSD (NCT01892345). The primary endpoint was time to first adjudicated relapse. The endpoints of relapse-related hospitalization rates and their associated treatment in each study group are described.
Methods: Patients with AQP4-IgG-positive NMOSD were randomized 2:1 to receive eculizumab (maintenance dose, 1200 mg/2 weeks, n=96) or placebo (n=47) with/without stable-dose concomitant immunosuppressant therapy (excluding rituximab and mitoxantrone). Hospitalizations were recorded as a component of the adverse event tracking performed throughout the study. The annualized relapse-related hospitalization and treatment rates were defined as the total number of relapses requiring hospitalization or treatment divided by the total number of patient-years in the study period.
Results: The median exposure to treatment was 89.43 weeks for eculizumab and 41.29 weeks for placebo. The overall annualized hospitalization rate was 0.26 and 0.78 (p< 0.0001) in the eculizumab and placebo groups, respectively. The annualized relapse-related hospitalization rate was lower in the eculizumab than in the placebo group: 0.04 versus 0.31, respectively, p< 0.0001. The annualized relapse-related use of intravenous methylprednisolone, plasma exchange and high-dose oral corticosteroids for eculizumab and placebo was 0.07 and 0.42 (p< 0.0001), 0.02 and 0.19 (p=0.0001) and 0.04 and 0.11 (p=0.0733), respectively.
Conclusions: Treatment with eculizumab reduced relapse-related hospitalizations and their associated treatment rates in patients with AQP4-IgG-positive NMOSD versus placebo, which may have a favourable effect on health resource utilization.
Disclosure: This trial was supported by Alexion Pharmaceuticals.
Dr Berthele reports compensations for clinical trials received by his institution from Alexion Pharmaceuticals, Biogen, Novartis Pharmaceuticals, Roche, Sanofi Genzyme and Teva Pharmaceuticals, and personal fees and non-financial support from Bayer Healthcare, Biogen, Merck Serono, Mylan, Novartis Pharmaceuticals, Roche and Sanofi Genzyme.
Dr Pittock reports grants, personal fees and non-financial support from Alexion Pharmaceuticals, grants from the Autoimmune Encephalitis Alliance and Grifols; grants, personal fees, non-financial support and other from MedImmune, Inc. Dr Pittock has a patent # 9,891,219 (application # 12-573942) 'Methods for treating neuromyelitis optica (NMO) by administration of eculizumab to an individual that is aquaporin-4 (AQP4)-IgG autoantibody positive'.
Dr Fujihara received consultancy/speaker fees from Alexion Pharmaceuticals, Asahi Kasei Medical, Biogen, Chugai, Eisai, Mitsubishi-Tanabe Pharma, Nihon, Novartis Pharmaceuticals, ONO Pharmaceutical, Takeda and Teijin.
Dr Kim received research support from Genzyme, Merck Serono, the Ministry of Science and ICT,
Teva-Handok and UCB; received consultancy/speaker fees from Celltrion, Eisai, HanAll BioPharma, MedImmune, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, and UCB; serves on a steering committee for MedImmune/VielaBio; is co-editor for the Multiple Sclerosis Journal - Experimental, Translational and Clinical, and associate editor for the Journal of Clinical Neurology.
Dr Levy receives research support from Alexion, Alnylam, Apopharma, Genzyme, Sanofi, Shire, Viela Biolabs (formerly MedImmune) and Viropharma, and he serves as a consultant for Alexion, Apopharma, Chugai, Genzyme, MedImmune, Quest Diagnostics and Shire.
Dr 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, Alexion, ARGENX, Bayer Schering, Biogen Idec, Chugai Pharma, EuroImmun, Genzyme, MedDay, MedImmune, Merck Serono, Novartis, Roche and Teva, and grants from Abide, Bayer Schering, Biogen Idec, Merck Serono, Novartis and Teva. She has received grants from EDEN, GMSI, the Guthy-Jackson Charitable Foundation, the John Fell Fund, MRC, the MS Society, NIHR and Oxford Health Services Research Committee for research studies.
Dr Nakashima reports personal fees from Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharmaceuticals and Takeda Pharmaceuticals; and grants from LSI Medience, the Ministry of Education, Science and Technology of Japan, and the Ministry of Health, Welfare and Labor of Japan.
Dr Totolyan reports personal fees from Bayer, Janssen, Merck, Receptos, Inc., Roche, Sanofi and Teva; grants and personal fees from Actelion, BIOCAD (Russia) and Novartis; and grants from GeNeuro.
Dr Terzi, Dr Viswanathan and Dr Wang have nothing to disclose.
Kerstin Allen, Marcus Yountz and Róisín Armstrong are employees of and hold stock in Alexion.
Dr Wingerchuk reports grants from Alexion Pharmaceuticals during the conduct of the study; and personal fees from Biogen, BrainStorm Therapeutics, Caladrius, Celgene, MedImmune, Novartis and ONO Pharmaceutical.