Impact of Eculizumab on Health Outcomes in Patients with Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder: Findings from the PREVENT Study

Objective: To examine health outcomes in terms of individual dimensions from the 5-dimension EuroQoL 3-level questionnaire (EQ-5D-3L): mobility, self-care, usual activities, pain/discomfort and anxiety/depression, for patients with neuromyelitis optica spectrum disorder (NMOSD) treated with the terminal complement inhibitor eculizumab. Background: Relapses in NMOSD can cause neurological deficits, resulting in significant negative health outcomes. In the phase 3, randomized, double-blind, placebo-controlled PREVENT study (NCT01892345) conducted in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-positive NMOSD, mean changes from baseline for the EQ-5D-3L visual analog scale score were 5.4 (standard deviation [SD], 18.53) for eculizumab and 0.6 (16.39) for placebo (p = 0.0309); corresponding changes for the EQ-5D-3L index score were 0.05 (0.179) and −0.04 (0.212), respectively (p = 0.0077). Design/Methods: Patients were randomized 2:1 to receive eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. At baseline and 4, 8, 12 and every 12 weeks thereafter until the end of the study, patients completed the EQ-5D-3L. For each dimension, the distribution of changes in patients reporting no, some or extreme problems between baseline and study end were analyzed post hoc using a randomization-based non-parametric analysis of covariance. Results: Of 143 patients randomized (eculizumab, n = 96; placebo, n = 47), the median age was 45.0 years and 90.9% were female. At baseline, most patients reported some or extreme problems in the EQ-5D-3L dimensions. These proportions were greatest for the dimension pain/discomfort (eculizumab, 81.25%; placebo, 82.98%) and least for self-care (eculizumab, 32.29%; placebo, 36.17%). Changes in the proportions reporting problems favored eculizumab over placebo for all dimensions. Differences were significant for usual activities (p = 0.0014), self-care (p = 0.0181) and pain/discomfort (p = 0.0359). Conclusions: In patients with AQP4-IgG-positive NMOSD, eculizumab improved health outcomes compared with placebo, measured as changes in patients reporting problems in EQ-5D-3L dimensions. Disclosure: Dr. 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. 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. 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. 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. 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. 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. 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. Shang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals (Employee). Dr. Shang holds stock and/or stock options in Biogen. 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. 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.