Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, relapsing, autoimmune, inflammatory disease of the central nervous system. Disability accumulates with repeated attacks, severely affecting quality of life. Inebilizumab, an anti-CD19 monoclonal B-cell–depleting antibody, was assessed in N-MOmentum, a randomized, placebocontrolled, double-masked trial in patients with NMOSD. Objectives: To assess the effectiveness of inebilizumab on disability outcomes in N-MOmentum and determine if severity of pre-existing disability influenced efficacy. Methods: Adults with NMOSD and an Expanded Disability Status Scale (EDSS) score ≤8 were randomized 3:1 to receive inebilizumab 300 mg or placebo on days 1 and 15. The randomized controlled period (RCP) was 28 weeks or up to an adjudicated attack. The proportion of patients with disability worsening (EDSS score change ≥2 from a baseline of 0, ≥1 from a baseline of 1-5, or ≥0.5 from a baseline of ≥5.5) was assessed by logistic regression. Change from baseline in modified Rankin Scale scores was analyzed by the Wilcoxon–Mann– Whitney odds approach. Subgroup analysis by baseline EDSS score of the primary outcome (time to adjudicated attack) was performed by Cox proportional hazards regression. Results: The median (range) baseline EDSS score of the 174 patients receiving inebilizumab was 3.5 (0-8) and 4.0 (1-8) for the 56 receiving placebo; 18.0% and 30.4% had disability worsening at week 12, respectively. At the end of RCP, 15.5% of patients on inebilizumab and 33.9% on placebo had disability worsening; odds ratio (95% CI): 0.370 (0.185-0.739); P = .0049. Of the 9632 paired comparisons, modified Rankin Scale outcomes at end of RCP were better with inebilizumab than placebo in 51.5% of cases and were equal in 21.9% of cases; adjusted odds ratio (95% CI): 1.663 (1.195-2.385); P = .0023. Inebilizumab reduced the risk of attack compared with placebo in patients with baseline EDSS score in the lower (<5) or upper half (≥5) of the 10-point scale; hazard ratios (95% CI): 0.257 (0.120-0.552); P = .0005 and 0.367 (0.137-0.981); P = .0456, respectively; the treatment effect was not significantly different (interaction test, P = .6363). Long-term, open-label follow-up data will be presented. Conclusions: In N-MOmentum, disability outcomes were significantly better with inebilizumab monotherapy than with placebo. Inebilizumab reduced the risk of attack in patients with NMOSD irrespective of the level of pre-existing disability.

Supported by: None
Disclosure: Dean Wingerchuk: Alexion Pharmaceuticals, Terumo BCT, GuthyJackson Charitable Foundation (contracted research); BrainStorm Therapeutics, Caladrius Biosciences, Celgene, MedImmune, Novartis, Ono Pharmaceutical (personal fees); Chugai Pharmaceutical (consulting fee); MedImmune, Viela Bio (a clinical trial adjudication committee). Romain Marignier: Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, Teva, Viela Bio (funding for travel and honoraria); MedImmune, Viela Bio (scientific advisory board). Jeffrey L. Bennett: AbbVie, Chugai, Clene Nanomedicine, Equillium, Frequency Therapeutics, Genentech, Genzyme, Alexion (personal fees); Aquaporumab (patent issued); EMD Serono, Novartis (grants and personal fees); MedImmune/Viela Bio (consulting fee); Guthy–Jackson Charitable Foundation, Mallinckrodt, National Institutes of Health (grants). Ho Jin Kim: Alexion, Celltrion, Eisai, HanAll BioPharma, MedImmune/Viela Bio, Merck Serono, Novartis (personal fees); Journal of Clinical Neurology and Multiple Sclerosis Journal (associate editor/co-editor); National Research Foundation of Korea (grants); Sanofi Genzyme, Teva-Handok (grants, personal fees). Brian Weinshenker: Alexion, MedImmune, Viela Bio (royalties, payments); Mitsubishi Tanabe Pharma (consulting fee); RSR Ltd, Oxford University, Hospices Civils de Lyon and MVZ Labor PD Dr Volkmann und Kollegen GbR (royalty). Sean J. Pittock: Alexion, Autoimmune Encephalitis Alliance, Grifols, Euroimmun, NIH RO1 NS065829-01, MedImmune/Viela Bio, Guthy-Jackson Charitable Foundation (consulting fees and research support); named inventor on filed patents that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker (receipt of intellectual property rights/patent holder). Kazuo Fujihara: Alexion, Bayer Schering, Biogen, Chugai, MedImmune, Merck Serono, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Novartis, Ono, Viela Bio (scientific advisory boards); Asahi Kasei Medical, Astellas, Bayer Schering, Biogen, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Novartis, Takeda (funding for travel and speaker honoraria); Asahi Kasei Medical, Bayer Schering, Biogen, ChemoSero-Therapeutic Research Institute, Chugai, Genzyme Japan, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Ono, Teijin, Teva, Ministry of Education, Culture, Sports, Science and Technology of Japan, Ministry of Health, Welfare and Labor of Japan (contracted research). Friedemann Paul: Bayer, Biogen, Merck Serono, Novartis, Sanofi Genzyme, Teva (research support, speaker honoraria, travel reimbursement); Guthy-Jackson Charitable Foundation (travel funding); Novartis (serves on steering committee); German Research Council (DFG Exc 257) and German Competence Network for Multiple Sclerosis (financial support). Gary Cutter: AMO Pharma, BioLineRx, Horizon Pharmaceuticals, Merck, Merck/Pfizer, National Heart, Lung, and Blood Institute (protocol review committee); National Institute of Child Health and Human Development (OPRU oversight committee); Neurim, OPKO Biologics, Orphazyme, Reata Pharmaceuticals, Receptos/Celgene, Sanofi-Aventis, Teva Pharmaceuticals (personal fees for participation on data and safety monitoring boards); Atara Biotherapeutics, Axon, Argenix, Biogen, Biotherapeutics, Brainstorm Cell Therapeutics, Charleston Laboratories Inc, Click Therapeutics, Genentech, Genzyme, GW Pharma, Klein Buendel Inc, MedDay, MedImmune, Novartis, Roche, SciFluor, Somahlution, Teva Pharmaceuticals, TG Therapeutics, UTHealth Houston (consulting fee); Pythagoras Inc, AL, USA (president of organization); Teva Neuroscience (grant); University of Alabama at Birmingham (salary). Ari Green: Bionure, Inception Sciences, JAMA Neurology, MedImmune/Viela Bio, Mylan, Synthon, Trims Pharma (other financial relationships [for activities as expert witness, associate editor, advisory board/steering committee participation and end point adjudication]); Conrad N. Hilton Foundation and Tom Sherak MS Hope Foundation (grants); Pipeline Therapeutics (personal fees from and other financial relationships). Orhan Aktas: Almirall, MedImmune, Merck Serono, Roche (personal fees). Bayer HealthCare, Biogen, Genzyme, Novartis, Teva, Viela Bio (grants and personal fees); German Research Foundation (DFG) and German Ministry of Education and Research (BMBF) (grants). Hans-Peter Hartung: Bayer HealthCare, Biogen, CSL Behring, GeNeuro, Genzyme, MedImmune, Merck Serono, Novartis, Opexa, Receptos, Roche, Sanofi, Teva, Viela Bio (consulting, speaking, serving on steering committees). Fred D. Lublin: AbbVie, Acorda, Actelion, Apitope, Atara Biotherapeutics, Bayer HealthCare, Biogen, BrainStorm Cell Therapeutics, EMD Serono, Forward Pharma, GW Pharmaceuticals, Innate Immunotherapeutics, Jazz Pharmaceuticals, MedDay, MedImmune/Viela Bio, Novartis, Orion Biotech, Polpharma, Receptos/Celgene, Roche/Genentech, TG Therapeutics (personal fees); Sanofi Genzyme, Teva Neuroscience (grants and personal fees); Transparency Life Sciences (grants). Maureen A. Mealy, Jorn Drappa, Gerard Barron, Soraya Madani, Dewei She, Daniel Cimbora, William Rees, John N. Ratchford, Eliezer Katz: Viela Bio (salary). Bruce A.C. Cree: Akili, Alexion, Biogen, GeNeuro, Novartis, Sanofi Genzyme, TG Therapeutics (consulting fee).
Keywords: Disease-modifying treatments in MS