Search

Objective: No head‐to‐head clinical trials have compared ofatumumab with other disease‐modifying therapies (DMTs) available in Japan for patients with relapsing multiple sclerosis (RMS). In this study, a network meta‐analysis (NMA) was conducted to compare the efficacy of ofatumumab to other DMTs currently available in Japan for the treatment of patients with RMS. Methods: Systematic searches were conducted in biomedical databases from inception to June 2020 to identify randomized controlled trials. Only English‐ and Japanese‐language publications describing studies conducted in Japan were included. Trials with sufficiently similar study and patient characteristics were included in a Bayesian NMA. A sensitivity analysis was conducted to explore the impact of potential sources of uncertainty. Results: Four trials, each comparing a DMT with placebo in a ≥50% Japanese population, were sufficiently similar that comparative efficacy could be assessed for annualized relapse rate (ARR). Ofatumumab numerically reduced ARR compared with fingolimod (rate ratio [RR]: 0.84, 95% credible interval [CrI]: 0.20–3.39), dimethyl fumarate (RR: 0.61, 95% CrI: 0.16–2.30), and placebo (RR: 0.41, 95% CrI: 0.12–1.39), but not natalizumab (RR: 1.33, 95% CrI: 0.33–5.45). In a subgroup analysis of Japanese patients only, ofatumumab reduced relapses compared with all other treatments including natalizumab. These results were limited by the lack of studies reporting direct comparisons between included treatments and by heterogenous reporting of outcome data. Conclusion: These findings, although limited by the paucity of evidence for Japanese patients, suggest that monoclonal antibody therapies (ie, natalizumab and ofatumumab) may provide improved efficacy compared with other DMTs available in Japan for patients with RMS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the two main autoimmune demyelinating disorders of the central nervous system. MS is defined as autoimmune oligodendrocytopathy (unknown autoantigens), and NMOSD is defined as autoimmune astrocytopathy or aquaporin‐4 channelopathy. Both diseases can occur throughout the central nervous system, and do often cause various "motor" and "non‐motor" symptoms. "Non‐motor" symptoms, including cognitive impairment, fatigue, pain and neuropsychological symptoms (e.g. depression, loneliness and anxiety), have gained renewed attention in MS and NMOSD since the past three decades, because they influence a patient's competence in daily life activities, including the participation in social activities and their employment status. Herein, we summarize the current concepts of the neuropathological processes of these "non‐motor" symptoms in MS and NMOSD. These concepts help to define the novel disease‐specific mechanisms of the two diseases, and to improve the quality of daily life of patients with MS and NMOSD. [ABSTRACT FROM AUTHOR]

Objective To understand, through an analysis of health insurance claims data, the current treatment status and medical cost of multiple sclerosis ( MS) in Japan. Methods We analyzed claims data (January 2005-January 2016) from the Japan Medical Data Center Co., Ltd., identifying MS patients, except those with neuromyelitis optica, using an algorithm based on diagnosis codes. Prescription drug usage and medical costs for MS patients were analyzed. Results A total of 713 MS patients were identified in the database. Between 2011 and 2015, the age-adjusted prevalence of MS in the database increased from 0.015% to 0.019%, and the female-to-male ratio increased from 1.70 to 2.03. The prescription rate for disease-modifying therapy drugs was higher in larger care settings. Prescriptions for fingolimod increased from 2011, with a concomitant decrease in prescriptions for interferon. The per patient per month cost for MS was ¥124 337 ( US$1190 or €1084, as of October 2016). This was higher than the costs for Parkinson's disease (¥84 410), myasthenia gravis (¥82 944) and rheumatoid arthritis (¥53 843). However, the total per member per month cost for MS, which represents the population-based economic impact, was ¥25.2, which was lower than the parallel costs for Parkinson's disease (¥123.0) and rheumatoid arthritis (¥311.6) because of the low prevalence of MS in Japan. Conclusions Using real-world data, we obtained up-to-date prevalence, treatment status and medical cost information for MS in Japan. The present results showed the efficacy of a real-world database to obtain the latest national trends for rare diseases, such as MS; this could have important implications for clinicians and policymakers. [ABSTRACT FROM AUTHOR]

The article offers information on the Third Annual Meeting of the Multiple Sclerosis (MS) Summer College held at the Kobe Portpia Hotel in Kobe, Japan from August 6-7, 2016. Topics discussed include pathomechanisms of neuromyelitis optica (NMO), role of fingolimod in bone resorption in female patients with MS, and diagnosis and treatment strategies in pediatric MS patients. Associate Professor Monika Bradl of the Medical University of Vienna in Austria gave the opening lecture on NMO.

Autoimmune disorders of the central nervous system often involve autoimmune inflammation of the anterior visual pathways. Autoimmune optic neuritis can be categorized as: (i) isolated optic neuritis; (ii) relapsing isolated optic neuritis: (iii) chronic relapsing inflammatory optic neuropathy; (iv) neuromyelitis optica spectrum disorders-associated optic neuritis; or (v) multiple sclerosis-associated optic neuritis. Studies of serum-specific autoantibodies, such as aquaporin-4 and myelin oligodendrocyte glycoprotein, have revealed some underlying mechanisms of autoimmune optic neuritis. However, the etiology and pathogenesis of most cases of autoimmune optic neuritis remain unclear. The following clinical features of autoimmune optic neuritis are profoundly affected by the unique structure of the human anterior visual pathways: (i) vulnerability to swelling of the intracanalicular optic nerve as a result of the limited space within the bony canal; (ii) inflammatory cell infiltration through the subarachnoid space, pia and pial septa; (iii) compartmentalized dynamics of cerebrospinal fluid as a result of the cul-de-sac anatomy of the optic nerve; (iv) permeability of the prelaminar optic nerve head as a result of the lack of classical blood-brain barrier characteristics; and (v) retinal abnormalities, which are a diagnostic window of neurodegenerative processes of the optic nerves and/or brain. Future studies are required to configure a systemic nosology for optic neuritis with international consensus, elucidate specific diagnostic biomarkers, carry out clinical trials of the acute and chronic phases of the disease etiologies, and elucidate possible neuroprotective and remyelinating treatments. [ABSTRACT FROM AUTHOR]

Objective To assist policymakers as they reflect on treatment protocols and approaches for the efficient delivery of medical care for multiple sclerosis (MS) patients in Japan. Methods We analyzed data from a large Japanese health insurance claims database. Using an algorithm based on diagnosis codes, all patients with a diagnosis of MS were identified; patients having a non- MS demyelinating disease were excluded from the population. MS patient data were used for cross-sectional analysis carried out on the data collected at a certain period. We identified a total of 1808 MS patients, and we analyzed data for 1133 patients with an observation period of ≥6 months from October 2013 to September 2014. Newly diagnosed MS patients were identified within the MS patients, and their data were used for longitudinal analysis, tracking each patient over a period of time. Results The total per patient per month cost for MS was ¥93 542 ( US$781, €695 as of October 2015). Disease-modifying therapy drugs costs constituted half of the overall medical costs. For newly diagnosed MS patients, hospitalization costs were the largest component in the initial month, while drug costs were the largest component more than several months after the initial visit. There was a positive correlation between relapse frequency and medical cost. Conclusions These results provide up-to-date information on the demographics, medical treatment and cost status of MS in almost real-time by using a claims database. They suggest that claims data analysis can effectively support medical policymaking. [ABSTRACT FROM AUTHOR]

Objective The aim of the present study was to investigate the association of magnetic resonance imaging ( MRI) findings and social activity with cognitive function in Japanese patients with multiple sclerosis ( MS). Methods The Brief Repeatable Battery of Neuropsychological tests ( BRB-N) was carried out in 184 Japanese patients with MS, and 163 controls matched for age, sex and education. MRI findings of cerebral, brainstem, and cerebellar lesions and social activities of MS patients were further examined. Results MS patients with higher numbers of cerebral lesions on MRI had lower scores in most BRB-N tests. BRB-N scores in the majority of tests were significantly lower in patients with brainstem and cerebellar lesions. Data from an analysis of variance model in which only the main effects of cerebral, brainstem and cerebellar lesions were hypothesized showed an association of cerebral lesions with decreased scores in all BRB-N tests, except symbol digit modalities test ( SDMT) and paced auditory serial addition test ( PASAT). In contrast, cerebellar lesions were associated with decreased SDMT and PASAT scores. Patients categorized as 'unemployed because of MS' had lower BRB-N scores than other social activity groups. Lower SDMT scores had an effect on the 'unemployed because of MS' group, whereas the Expanded Disability Status Scale had a significantly greater negative impact on patients in this social category. Conclusions Higher numbers of brain lesions on MRI could have an impact on cognitive function in patients with MS, and impairment of information processing appears significantly associated with cerebellar lesions. Cognitive impairment affects the employment status of patients with MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis ( MS) and neuomyelitis optica ( NMO) are the two main autoimmune and inflammatory diseases of the central nervous system. They have long been considered to be autoimmune diseases that primarily affect the white matter ( WM). However, renewed interest in gray matter ( GM) pathology is emerging. This review focuses on the current knowledge of the details of GM pathology, and its clinical aspects including cognitive impairment in MS and NMO. Patients with MS and NMO have similar cognitive profiles as represented by the latent start of impairment from a very early stage of the disease course. Pathological assessments show that substantial cortical demyelination is prominent in all stages or courses of MS, and cortical neurodegeneration is also present not only in cortical demyelination, but also in normal-appearing GM in MS. In contrast, cortical neurodegeneration is present in NMO and involves unique dynamics of astrocytes, but no cortical demyelination is seen in NMO. Thus, two distinct diseases, MS and NMO, each have unique characteristic features of pathological modalities in the brain. These important hallmarks of MS and NMO might influence neuronal and cognitive function in the brain, given different detrimental effects including cytokine diffusion, disruption of water homeostasis associated with aquaporin-4 dynamics, or other unidentified mechanisms. Although the cause of GM lesions in MS and NMO has not been fully determined, an increase in knowledge of the structure of GM lesions, and the pathomechanisms in MS and NMO brains will result in more targeted pharmacotherapeutic approaches to these diseases. [ABSTRACT FROM AUTHOR]

Objectives There has been no large-scale study of methylprednisolone pulse therapy in Asian patients with multiple sclerosis ( MS) or neuromyelitis optica ( NMO), despite it being widely used for acute relapse. We aimed to clarify treatment response of MS and NMO patients to methylprednisolone pulse therapy and post-pulse oral corticosteroids in real clinical practice in a multicenter study in Japan. Methods Investigators at 28 institutions collected changes in neurological symptoms/signs and Expanded Disability Status Scale ( EDSS) scores before and within 1 week of completion of methylprednisolone pulse therapy carried out in 2010, and after post-pulse oral corticosteroids therapy, by retrospective review of medical records. Results In 345 patients (95.1% of all registered patients), 457 series of methylprednisolone pulse therapy were carried out for treatment of acute relapse. EDSS scores improved by 0.8 ± 1.1 (mean ± SD) after the first course. The second and third courses also produced sufficient improvements (by 0.7 and 0.6, respectively), but much smaller improvements were observed thereafter. The target neurological symptoms and signs improved in 79.5% of patients. Improvement rates were 5-20% lower after a course of pulse therapy than after a series of pulse therapy. A half dose (500 mg/day) produced less improvement than a standard dose (1000 mg/day; 65.9 vs 79.5%). During post-pulse oral corticosteroid therapy, EDSS scores decreased by 0.6 ± 0.9. No significant adverse effects were observed. Conclusions Methylprednisolone pulse therapy is beneficial in nearly 80% of Japanese MS and NMO patients, and EDSS score improvements after therapy are compatible with those in Western MS patients. [ABSTRACT FROM AUTHOR]

The article discusses Immune-mediated hypertrophic pachymeningitis (HP) and presents the clinical significance of anti-neutrophil cytoplasmic antibody and Wegener's granulomatosis. Topics mentioned include autoimmune diseases, infections, syphilis and bacterial diseases such as tuberculosis and neoplasms like lymphoma. A study on patients with HP is presented with observations namely predominance in elderly females, presence of garnulomatosis with polyangiitis and lesions in dura mater.

The article focuses on a study based on pathomechanism of Neuromyelitis optica spectrum disorder (NMOSD). Topics discussed include effector mechanisms of aquaporin-4 (AQP4) antibody binding to its cellular target astrocytes which include complement dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and internalization of AQP4 channels; pattern-specific loss of AQP4 immunoreactivity on astrocytes; and melastatin 4 in the optic nerves of NMOSD.

The article focuses on the cortical degeneration as potential pathogenesis of cognitive impairment in neuromyelitis optica (NMO). It reports on a study during which 57 percent of the NMO spectrum disorder (NMOsd) patients and 47 percent of the multiple sclerosis (MS) patients showed impaired performance by an assessment through a neuropsychological test. It states that further research is needed to investigate the essential mechanisms of cognitive impairment and neurodegeneration.