Abstract: P1343

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

J. Palace¹, S.J. Pittock², A. Berthele³, K. Fujihara^4,5,6, H.J. Kim⁷, M. Levy^8,9, I. Nakashima^4,10, M. Terzi¹¹, N. Totolyan¹², S. Viswanathan¹³, K.-C. Wang^14,15, A. Pace¹⁶, M. Yountz¹⁶, R. Armstrong¹⁶, D.M. Wingerchuk¹⁷, The PREVENT Study Group

¹University of Oxford | John Radcliffe Hospital | Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom, 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, Research Institute and Hospital of National Cancer Center, Goyang, Republic of Korea, ⁸Department of Neurology, Johns Hopkins University, Balitmore, MD, ⁹Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, 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: Patients with neuromyelitis optica spectrum disorder (NMOSD) accumulate significant disability from NMOSD relapses. PREVENT was a global, randomized, double-blind, placebo-controlled study, designed to evaluate the efficacy and safety of eculizumab in aquaporin-4 immunoglobulin G-positive NMOSD. The primary endpoint was time to first adjudicated relapse. Secondary outcomes included the impact of eculizumab on disability measures. Here, we summarize findings from an analysis of the Expanded Disability Status Scale (EDSS), the modified Rankin Scale (mRS) and the Hauser Ambulation Index (HAI).
Methods: Patients were randomized to eculizumab (maintenance dose, 1200 mg/2 weeks, n=96) or placebo (n=47) with/without stable-dose concomitant immunosuppressant therapy (excluding rituximab and mitoxantrone). Disability assessments were performed at baseline, at weeks 4, 8 and 12, and every 12 weeks thereafter until study end. Changes in disability were assessed by the EDSS, the mRS, which measures the degree of disability in daily activities (scores range from 0 to 6), and the HAI, which assesses walking mobility (scores range from 0 to 9). Higher scores indicated worse disability.
Results: At baseline, median (range) scores for EDSS (4.0 [1.0-7.0]), mRS (2 [0-4]) and HAI (2 [0-8]) indicated that patients had moderate-to-severe disability; treatment groups were similarly distributed. For eculizumab compared with placebo, mean change in EDSS from baseline to study end was -0.18 (standard deviation [SD] 0.814) versus 0.12 (SD 0.945); p=0.0597, for mRS, mean change was -0.2 (0.72) versus 0.1 (SD 0.75); p=0.0154 and for HAI, mean change was -0.4 (SD 1.08) versus 0.5 (SD 1.61); p=0.0002. The distribution for the change from baseline to end of study in EDSS score showed 51.0% of the eculizumab-treated patients and 42.6% of the placebo-treated patients had no change, 29.2% of the eculizumab-treated patients and 29.8% of the placebo-treated patients had a ≥0.5-point improvement in EDSS score, while 19.8% of the eculizumab-treated patients and 27.7% of the placebo-treated patients had a ≥0.5-point worsening in EDSS score.
Conclusions: Overall, results for disability endpoints showed effects that consistently favoured eculizumab over placebo. The distribution of changes from baseline in disability scores showed that patients in the eculizumab group tended to have no change or more improvement, whereas patients in the placebo group tended toward more worsening.
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.