Abstract: P612

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

A. Berthele¹, S.J. Pittock², K. Fujihara^3,4,5, H.J. Kim⁶, M. Levy^7,8, J. Palace⁹, I. Nakashima^3,10, 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

¹Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ²Department of Neurology, Mayo Clinic, Rochester, MN, United States, 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, ⁶Department of Neurology, Research 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, 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, ¹⁷Mayo Clinic, Scottsdale, AZ, United States

Introduction: Relapses in patients with neuromyelitis optica spectrum disorder (NMOSD) can cause neurological deficits, reducing quality of life (QoL). Eculizumab is a terminal complement inhibitor that improves QoL in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive NMOSD. In the Phase 3, randomized, double-blind PREVENT study (NCT01892345), mean change from baseline for 5-dimension EuroQoL questionnaire (EQ-5D) visual analogue scale (VAS) score was 5.4 (standard deviation [SD] 18.5) and 0.6 (SD 16.4) with eculizumab and placebo, respectively, p=0.0309; the change for EQ-5D index score was 0.05 (SD 0.18) and −0.04 (SD 0.21), p=0.0077. The primary endpoint of time to first adjudicated relapse was significantly improved with eculizumab versus placebo. Secondary and tertiary outcomes included various QoL assessments. We present an analysis of 36-item Short-Form Health Survey (SF-36) scores in PREVENT.
Methods: Adults 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). At baseline, 4, 8, 12 and every 12 weeks thereafter until end of study (EOS)/relapse, patients completed the SF-36, and scores were analyzed using a randomization-based non-parametric analysis of covariance.
Results: Of 143 patients randomized, the median age was 45.0 years and 90.0% were female. At baseline, mean physical component scores (PCS) for eculizumab and placebo were 38.6 (9.8) and 36.9 (10.8), respectively, and changed from baseline to EOS by 3.36 (7.73) and 0.70 (8.25), respectively (p=0.0210). At baseline, mean mental component scores (MCS) for eculizumab and placebo were 47.0 (12.5) and 44.0 (11.4), respectively, and changed from baseline to EOS by 0.45 (10.60) and −0.06 (11.79), respectively (p=0.2942). Eculizumab improved all SF-36 scale scores versus placebo from baseline to EOS, with significant improvements for physical functioning (p=0.0328) and role physical (p=0.0455).
Conclusions: Eculizumab substantially improved QoL compared with placebo in patients with AQP4-IgG-positive NMOSD. Changes in PCS and MCS sub-scales suggest improvements in QoL observed with SF-36 were driven by physical components of the survey; this is not unexpected, as NMOSD relapses cause physical impairment. Long-term follow-up in the open-label extension of PREVENT will help further characterize the benefits of eculizumab in NMOSD.
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, 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, Inc.; grants from Grifols, Autoimmune Encephalitis Alliance; 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, Chugai, Asahi Kasei Medical, Biogen, Eisai, Mitsubishi-Tanabe Pharma, Nihon, Novartis Pharmaceuticals, ONO Pharmaceutical, Takeda, and Teijin.
Dr Kim received research support from the Ministry of Science & ICT, Genzyme, Merck Serono, 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 a co-editor for the Multiple Sclerosis Journal - Experimental, Translational, and Clinical, and an associated editor for the Journal of Clinical Neurology.
Dr Levy currently receives research support from: the National Institutes of Health, Maryland Technology Development Corporation, Sanofi, Genzyme, Alexion, Alnylam, Shire, Acorda and Apopharma. He also received personal compensation for consultation with Alexion, Acorda, and Genzyme and he serves on the scientific advisory boards for Alexion, Acorda 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 honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmun, MedDay, Abide and ARGENX, and grants from Merck Serono, Novartis, Biogen Idec, Teva, Abide and Bayer Schering. she has received grants from the MS society, Guthie Jackson Foundation, NIHR, Oxford Health Services Research Committee, EDEN, MRC, GMSI, and John Fell for research studies.
Dr. Nakashima reports personal fees from Mitsubishi Tanabe Pharma, personal fees from Biogen Japan, personal fees from Takeda Pharmaceuticals, personal fees from Novartis Pharmaceuticals, grants from LSI Medience, grants from Ministry of Education, Science and Technology of Japan, and the Ministry of Health, Welfare and Labor of Japan.
Dr. Totolyan reports personal fees from Roche, personal fees from Sanofi, grants and personal fees from Novartis, personal fees from Merck, personal fees from Bayer, grants from GeNeuro, grants and personal fees from Actelion, personal fees from Teva, personal fees from Receptos, Inc., personal fees from Janssen, grants and personal fees from Biocad (Russia).
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; personal fees from MedImmune, personal fees from Celgene, personal fees from Novartis, personal fees from ONO Pharmaceuticals, personal fees from BrainStorm Therapeutics, personal fees from Caladrius, personal fees from Biogen.