Abstract: P605

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

S. Pittock¹, A. Berthele², K. Fujihara^3,4,5, H.J. Kim⁶, M. Levy^7,8, J. Palace⁹, M. Terzi^3,10,11, 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

¹Department of Neurology, Mayo Clinic, Rochester, MN, United States, ²Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ³Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, ⁴Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine, Fukushima City, ⁵MS & NMO Center, Southern TOHOKU Research Institute for Neuroscience (STRINS), Koriyama, Japan, ⁶Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea, ⁷Department of Neurology, Johns Hopkins University, Balitmore, 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, ¹⁰Medical Faculty, Ondokuz Mayıs University, Samsun, Turkey, ¹¹Department of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan, ¹²First 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 PREVENT was a global, phase 3, randomized, double-blind, time-to-event study (NCT01892345) comparing the efficacy and safety of eculizumab and placebo in patients with aquaporin-4 immunoglobulin G-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD). Eculizumab was found to reduce the overall risk of adjudicated NMOSD relapse by 94.2% compared with placebo (hazard ratio [HR]: 0.058, 95% confidence interval [CI]: 0.017-0.197; p < 0.0001). The proportions of patients experiencing an adjudicated relapse in the eculizumab and placebo groups overall were 3/96 (3.1%) and 20/47 (42.6%), respectively. Here, we report the effectiveness of eculizumab in pre-specified subgroups. Methods Adults with NMOSD were randomized to eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo, with stable-dose concomitant immunosuppressant therapy (IST; except rituximab and mitoxantrone) permitted. Pre-specified IST subgroups were: corticosteroids alone; azathioprine (AZA) with/without corticosteroids; mycophenolate mofetil (MMF) with/without corticosteroids; other IST; no IST; and historic rituximab use. Pre-specified regional subgroups were Europe, Asia-Pacific and the Americas. Other subgroups included age, race and gender. Results Treatment with eculizumab reduced the proportions of patients experiencing an adjudicated relapse across all subgroups, including the no IST and historic rituximab use subgroups, and by age, race and gender. The proportions of patients with an adjudicated relapse in the eculizumab and placebo groups, respectively, among patients receiving corticosteroids alone (n = 27) were 0/16 (0.0%) and 4/11 (36.4%); in the AZA subgroup (n = 50) these proportions were 2/37 (5.4%) and 5/13 (38.5%), and in the MMF subgroup (n = 25) these proportions were 1/17 (5.9%) and 3/8 (37.5%). The proportions of patients with an adjudicated relapse in the eculizumab and placebo groups, respectively, among those from Europe (n = 51) were 1/32 (3.1%) and 12/19 (63.2%); in those from Asia-Pacific (n = 48), proportions were 1/35 (2.9%) and 5/13 (38.5%), and in those from the Americas (n = 44), proportions were 1/29 (3.4%) and 3/15 (20.0%). Conclusions The robust treatment effect of eculizumab on relapse risk reduction was observed across all pre-specified subgroups, including IST use as well as no IST use, geographic region, age, race and gender.
Disclosure: This trial was supported by Alexion Pharmaceuticals.
Dr Pittock reports grants, personal fees and non-financial support from Alexion Pharmaceuticals; grants from the Autoimmune Encephalitis Alliance and Grifols; and 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 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 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 & 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 Acorda, Alexion, Alnylam, Apopharma, Genzyme, Maryland Technology Development Corporation, the National Institutes of Health, Sanofi and Shire. He also received personal compensation for consultation with Acorda, Alexion and Genzyme, and serves on the scientific advisory boards for Acorda, Alexion and Quest Diagnostics.
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 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 Foundation, the John Fell Fund, the 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.
Amy Pace, Marcus Yountz and Róisín Armstrong are employees of 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.