Benefit of Eculizumab for a Broad Range of Patients with Aquaporin-4 Antibody-positive Neuromyelitis Optica Spectrum Disorder: Findings from the Phase 3 PREVENT Study

Objective: To determine whether eculizumab’s beneficial effect in reducing relapse risk in patients with neuromyelitis optica spectrum disorder (NMOSD) is associated with time since diagnosis, relapse history, disability burden or prior immunosuppressant therapy (IST) use, based on data from the phase 3 trial PREVENT (NCT01892345). Background: Antibodies to the aquaporin-4 (AQP4) water channel in NMOSD are reported to trigger the complement cascade, which is implicated in neuronal injury. The terminal complement inhibitor eculizumab is the first treatment approved for use in patients with AQP4-immunoglobulin G-positive NMOSD, based on PREVENT data. Design/Methods: In PREVENT, patients received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo, with stable-dose concomitant IST (except rituximab and mitoxantrone) permitted. PREVENT was not powered for subgroup analyses; post hoc descriptive analysis was performed on subgroups defined by time since diagnosis, total number of historical relapses, baseline Expanded Disability Status Scale (EDSS) score and prior IST use. Results: The proportions of patients experiencing an adjudicated relapse were lower with eculizumab than with placebo in all subgroups. Proportions for eculizumab and placebo, respectively, were: 2/31 versus 6/12 for Conclusions: The data from this post hoc subgroup analysis suggest that eculizumab reduced relapse risk in PREVENT compared with placebo, regardless of time since NMOSD diagnosis, relapse history, disability burden or prior IST use. Disclosure: Dr. Fujihara has received personal compensation from Alexion, Asahi Kasei Medical, Astellas, Bayer Schering, Biogen Idec, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Medimmune, Merck Serono, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Novartis, Ono, Takeda and Viela Bio. Asahi Kasei Medical, Bayer Schering, Biogen Idec, Chugai, Genzyme Japan, Mitsubishi Tanabe Pharma, Nihon Pharmaceutical, Ono, Teijin and TevaDr. Berthele has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals, Bayer Healthcare, Celgene, Biogen, Merck Serono, Novartis Pharmaceuticals, Roche. Dr. Berthele has received research support from Novartis. Dr. Kim has received personal compensation from Bayer Schering Pharma, Biogen, Eisai, HanAll BioPharma, MedImmune/Viela Bio, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok, UCB Dr. Kim has received personal compensation in an editorial capacity for Co-editor/associate editor from Journal of Clinical Neurology; Multiple Sclerosis Journal – Experimental, Translational and Clinical. Dr. Kim has received research support from Sanofi Genzyme, Teva-Handok, UCB.Dr. Levy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Viela Vio, Roche/Genentech, Mitsubishi Pharmaceuticals, TG Therapeutics, Clene. Dr. Levy has received personal compensation in an editorial capacity for Elsevier. Dr. Levy has received research support from Alexion, Shire, Alnylam. Dr. Nakashima has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisory board: Alexion Japan, Biogen Japan, Novartis Japan. Speaker honoraria: Biogen Japan, Novartis Japan, Mitsubishi Tanabe, Eisai, Takeda. Dr. Nakashima has received research support from LSI medience. Dr. Oreja Guevara has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Honoraria for speaking and/or consultancy from Biogen, Sanofi- Genzyme, Merck, Roche, Teva, and Novartis. Dr. Palace has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmun, MedDay, Abide and ARGENX.. Dr. Palace has received research support from MS society, Guthie Jackson Foundation, NIHR, Oxford Health Services Research Committee, EDEN, MRC, GMSI, and John Fell. Dr. Pittock has received personal compensation from Alexion, Grifols, Euroimmun, MedImmune/Viela Bio Dr. Pittock has received research support from Alexion, Grifols, Euroimmun, MedImmune/Viela BioDr. Terzi has nothing to disclose. Dr. Totolyan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Personal fees for lectures from Roche, Sanofi, Merck, Biocad (Russia); personal fees for clinical trials conduction from Roche, Sanofi, Receptos Inc, Biocad (Russia).. Dr. Viswanathan has nothing to disclose. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Sanofi, Eisai. Dr. Pace has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Yountz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Yountz holds stock and/or stock options in Alexion Pharmaceuticals (Employee) which sponsored research in which Dr. Yountz was involved as an investigator. Dr. Miller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Miller holds stock and/or stock options in Alexion Pharmaceuticals which sponsored research in which Dr. Miller was involved as an investigator. Dr. Tanvir has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Tanvir holds stock and/or stock options in Alexion Pharmaceuticals which sponsored research in which Dr. Tanvir was involved as an investigator. Dr. Armstrong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Wingerchuk has received personal compensation from BrainStorm Therapeutics, Caladrius Biosciences, Celgene, Chugai Pharmaceutical, MedImmune, Novartis, ONO Pharma-ceutical, Viela Bio. Dr. Wingerchuk has received personal compensation in an editorial capacity for OXP. Dr. Wingerchuk has received research support from Alexion Pharmaceuticals, Terumo BCT.