Safety and Effectiveness of Satralizumab in Japanese Patients with Neuromyelitis Optica Spectrum Disorder: A 6-month Interim Analysis of Post-marketing Surveillance.

INTRODUCTION: Satralizumab, an anti-interleukin-6 receptor antibody, is approved in Japan for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and is undergoing post-marketing surveillance (PMS) of clinical use. We aimed to describe the real-world safety and effectiveness of satralizumab in Japanese patients with NMOSD. METHODS: This is an ongoing PMS (planned completion: February 2027). This 6-month interim analysis assessed the safety and effectiveness of satralizumab in Japanese patients with NMOSD using data collected from August 2020 to July 2021. RESULTS: Among 570 patients who participated, 523 (91.75%) were female and the mean ± standard deviation (SD) age was 52.4 ± 14.1 years. At baseline, NMOSD expanded disability status scale mean ± SD was 4.19 ± 2.19; 490 (85.96%) patients used glucocorticoids and 277 (48.59%) patients used immunosuppressants concomitantly. Of 570 satralizumab-treated patients, 85 (14.91%) had discontinued satralizumab treatment at 6 months. For the overall adverse drug reactions (ADRs), 76.22 (66.07-87.48) events/100 person-years occurred in 118 (20.70%) patients, and infections occurred in 28 (4.91%) patients. Serious infections occurred in 18 (3.15%) patients, with an event rate of 9.05 (5.80-13.47) events/100 person-years. Of the 24 events of serious infections, respiratory tract infections (29.17%; 7) and urinary tract infections (25.00%; 6) were the most common serious infection events. One fatal ADR (septic shock) suspected to be related to satralizumab was reported. The mean ± SD glucocorticoid dose reduced from 12.28 ± 10.17 mg/day at the index date to 8.11 ± 7.30 mg/day at 6 months. The Kaplan-Meier cumulative relapse-free rate (95% confidence interval) was 94.59% (92.25-96.23) at 6 months. CONCLUSION: In this study, satralizumab was found to be safe, well tolerated, and effective in patients with NMOSD in routine clinical practice. The results are consistent with those of previous clinical trials. The safety and effectiveness of satralizumab in Japanese patients with NMOSD will be analyzed over the 6-year surveillance period. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000041047.

Hemodynamic recognition of pure autonomic failure: A case report.

Neurogenic orthostatic hypotension (OH) causes severe orthostatic intolerance. We evaluated hemodynamic parameters in a patient with pure autonomic failure (PAF) using various unique approaches. A 60-year-old woman had worsening light-headedness, fatigue, and severe OH without compensatory tachycardia. PAF was diagnosed based on negative neurological findings, testing, and imaging results. The active standing test did not increase the heart rate (HR), and it decreased cardiac output, indicating impaired sympathetic control of cardiovascular activity. HR did not change during the supine bicycle exercise stress test, whereas blood pressure decreased. The patient had an accentuated reaction to isoproterenol but did not respond to atropine sulfate. Isoproterenol 0.01 µg/kg/min caused a 153 % increase in HR that required more than 30 min to return to its original value, suggesting hypersensitivity to catecholamines and decreased parasympathetic activity. As for why atropine sulfate (0.04 mg/kg) did not increase HR, we assumed that parasympathetic activity was already suppressed or the sympathetic effects were not predominant. Intravenous atropine sulfate may be useful in diagnosing PAF, which generally lacks specific neurological physical findings. A proper understanding of the hemodynamics involved in the management of PAF-associated OH is crucial. Learning objective: The autonomic control of cardiovascular function is impaired in pure autonomic failure, and neurogenic orthostatic hypotension can be diagnosed by evaluating changes in heart rate. Treatment should be based on the hemodynamic characteristics using non-invasive cardiac output monitoring, pharmacological approaches, and supine bicycle exercise stress tests.

The burden of multiple sclerosis in Japan.

AIMS: Multiple sclerosis (MS) is a disabling autoimmune disease affecting the central nervous system. Few studies have examined the effect of MS on patient outcomes in Japan. The study aim was to quantify MS burden in Japan by comparing MS respondents to matched controls on patient outcomes. MATERIALS AND METHODS: Data from seven administrations of the nationally representative Japan National Health and Wellness Survey (2009-2014 and 2016) were used (n = 181,423). Respondents self-reporting MS diagnosis were compared with respondents not reporting MS. Matched controls were selected using propensity scores. Respondents with MS and matched controls were compared on health-related quality-of-life (HRQoL), work productivity and activity impairment, healthcare resource utilization, and costs. Comparisons were made using Chi-square tests or one-way ANOVAs. RESULTS: A total of 96 respondents with MS and 480 matched controls were included in the analyses. MS respondents reported worse mental (44.35 vs 47.51, p < .05), physical (33.11 vs 49.04, p < .001), and role (37.78 vs 47.11, p < .001) component summary scores (minimally important difference is 3.0). Additionally, MS respondents reported decrements on every health profile sub-scale (p < .001) and 5-Level EuroQoL-5 Dimensions outcome (p < .01). MS respondents also reported more healthcare provider visits (13.78 vs 6.13) and hospitalizations (3.02 vs 0.70; both, p < .001), leading to higher direct costs. For work productivity and activity impairment, MS respondents reported more absenteeism (17.50% vs 5.57%), presenteeism (38.11% vs 21.62%), overall work impairment (46.68% vs 25.27%), and activity impairment (46.88% vs 24.90%, all, p < .001), leading to higher indirect costs. LIMITATIONS: Japan NHWS data are cross-sectional, and causal relationships cannot be established. Due to the self-reported nature of the data, responses could not be independently verified. CONCLUSIONS: Results suggest MS in Japan is associated with poorer HRQoL and greater work and activity impairment, healthcare resource use, and costs. Improved MS management could benefit both patients and society.

Two subtypes of optic-spinal form of multiple sclerosis in Japan: clinical and laboratory features.

Seventy-seven cases of the optic-spinal form of multiple sclerosis (OSMS) were collected from 6 institutes in 3 cities of Japan, and the clinical and MRI features were analyzed. Two-thirds of the OSMS patients had longitudinally extensive spinal cord MRI lesions (LESL), and had clinical features similar to those of relapsing neuromyelitis optica which often causes severe disability. In contrast, OSMS patients without LESL tended to have milder disease and had some feature commonly seen in the conventional form of MS. The percentage of OSMS without LESL in total OSMS has recently been increasing. The present study suggests that LESL is crucially important for distinguishing the two subtypes of OSMS.