K. Fujihara
Fukushima Medical UniversityKazuo Fujihara, M.D.is Professor, Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine, and Director, Multiple Sclerosis & Neuromyelitis Optica Center, Southern TOHOKU Research Institute for Neuroscience (STRINS), Koriyama, Japan. Dr. Fujihara is a neurologist and has mainly worked in the field of multiple sclerosis (MS), neuromyelitis optica (NMO) and related neuroimmunological disorders. He is a member of the International Panel on Diagnosis of MS (the 2010 and 2017 revisions to the McDonald Criteria) and the International Panel on NMO Diagnosis (the 2015 International Consensus Diagnostic Criteria of NMOSD). Since 2013, he has served on the Executive Committee, International Medical and Scientific Board of The Multiple Sclerosis International Federation (MSIF), and the Board of European Charcot Foundation (ECF). He is an inaugural member and President (2018~) of Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS), President (2019~) of Japanese Society for Neuroimmunology (JSNI), an honorary member of The Association of Sri Lankan Neurologists (Honorary Member, 2012~), Indian Academy of Neurology (Honorary Corresponding Member, 2015~) and Hong Kong Society of Multiple Sclerosis (Honorary Fellow, 2015~), an Editorial Board member of Neurology: Neuroimmunology and Neuroinflammation (2018~) and Multiple Sclerosis and Related Disorders (2020~), and Associate Editor of Frontiers in Neurology (section Multiple Sclerosis and Neuroimmunology, 2017~).
Author Of 2 Presentations
FC01.01 - Long-term efficacy and safety of eculizumab monotherapy in AQP4+ neuromyelitis optica spectrum disorder
Abstract
Background
In the randomized, double-blind, placebo-controlled, phase 3 PREVENT trial (NCT01892345), eculizumab was well tolerated and significantly reduced relapse risk vs placebo in patients with aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). The treatment effect observed in a prespecified subgroup of patients who received eculizumab monotherapy vs placebo alone (i.e. without concomitant immunosuppressive therapy [IST]) was consistent with the overall population.
Objectives
To examine the long-term efficacy and safety of eculizumab monotherapy in patients with AQP4+ NMOSD during PREVENT and/or its ongoing open-label extension (OLE; NCT02003144).
Methods
During PREVENT and its OLE, adults with AQP4+ NMOSD received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (PREVENT only) with/without concomitant IST. Relapses, hospitalizations, IST changes and adverse events (AEs) with eculizumab monotherapy (PREVENT and its OLE; interim data cut-off, July 31, 2019) or with placebo alone (PREVENT) were descriptively analyzed post hoc.
Results
During PREVENT and/or its OLE, 33 patients received eculizumab monotherapy for a total of 85.3 patient-years (PY). Adjudicated relapses occurred in 1/33 patients (annualized relapse rate [ARR], 0.012; 95% confidence interval [CI]: 0.002–0.082), vs 7/13 with placebo alone in PREVENT. At 192 weeks, 96.2% of patients who received eculizumab monotherapy were relapse-free (95% CI: 0.757–0.994) vs 93.8% of patients who received eculizumab with concomitant IST (95% CI: 0.867–0.972). No patients receiving eculizumab monotherapy required hospitalization for a relapse and none started an IST. The treatment-related AE rate with eculizumab monotherapy in PREVENT and its OLE was similar to that with placebo alone in PREVENT (181.0 and 186.0 events/100 PY, respectively), the infection rate was similar between these groups (174.1 vs 186.0 events/100 PY), and the treatment-related serious AE rate was lower with eculizumab monotherapy than with placebo alone (5.7 vs 23.3 events/100 PY). No meningococcal infections or deaths occurred among these patients.
Conclusions
A very high proportion of patients who had experienced 1–2 relapses in the pre-study year remained relapse-free through 192 weeks of eculizumab monotherapy. Long-term eculizumab monotherapy was well tolerated. These data support the long-term effectiveness of eculizumab monotherapy in reducing relapse risk in AQP4+ NMOSD.
FC01.02 - Efficacy and safety of eculizumab in patients with neuromyelitis optica spectrum disorder previously treated with rituximab: findings from PREVENT
Abstract
Background
In PREVENT, eculizumab was associated with a significant reduction in relapse risk versus placebo and was well tolerated. In total, 46 patients (26/96 in the eculizumab arm, 20/47 in the placebo arm) were previously treated with the monoclonal antibody rituximab.
Objectives
To describe the efficacy and safety of eculizumab in patients in the PREVENT trial (NCT01892345) who had previously received rituximab.
Methods
Adults with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo with/without concomitant immunosuppressive treatment (except rituximab/mitoxantrone). A post hoc descriptive analysis was performed using data from patients with any prior rituximab treatment (within the previous year only for review of adverse events [AEs]) recorded more than 3 months before randomization.
Results
Baseline characteristics of the prior-rituximab subgroup were similar to those of the total PREVENT population; however, the subgroup included a lower proportion of Asian patients (10.9% vs 36.4% in total PREVENT) and greater representation from the Americas (58.7% vs 30.8%). In the subgroup, median times from last dose of rituximab to meningococcal vaccination and to first dose of study treatment were 31.7 and 38.7 weeks, respectively. Adjudicated relapses occurred in 1/26 patients (3.8%) and 7/20 patients (35.0%) in the eculizumab and placebo arms (hazard ratio: 0.093; 95% confidence interval: 0.011–0.755; p = 0.0055), respectively. Rates of AEs for eculizumab and placebo were 1025.8 and 1029.1 events/100 patient-years (100% of patients), respectively, and rates of serious AEs were 46.9 and 66.0 events/100 patient-years (38.9% and 47.1% of patients), respectively. Serious infections/infestations were recorded in 2/18 patients (11.1%) and 2/17 patients (11.8%) in the eculizumab and placebo arms, respectively.
Conclusions
In patients in PREVENT who had previously received rituximab, the risk of adjudicated relapse was significantly lower with eculizumab than with placebo. Rates of serious infections were similarly low with eculizumab and placebo.