Therapeutic Advances in Neurological Disorders最新文献

{"title":"Differential risk factor profile and neuroimaging markers of small vessel disease between lacunar ischemic stroke and deep intracerebral hemorrhage.","authors":"Yajun Cheng, Maria Del C Valdés Hernández, Mangmang Xu, Shuting Zhang, Xiaohua Pan, Baoqiang An, Joanna M Wardlaw, Ming Liu, Bo Wu","doi":"10.1177/17562864241253901","DOIUrl":"10.1177/17562864241253901","url":null,"abstract":"<p><strong>Background: </strong>Lacunar ischemic stroke (LIS) and deep intracerebral hemorrhage (dICH) are two stroke phenotypes of deep perforator arteriopathy. It is unclear what factors predispose individuals with deep perforator arteriopathy to either ischemic or hemorrhagic events.</p><p><strong>Objectives: </strong>We aimed to investigate risk factors and neuroimaging features of small vessel disease (SVD) associated with LIS <i>versus</i> dICH in a cross-sectional study.</p><p><strong>Methods: </strong>We included patients with clinically presenting, magnetic resonance imaging-confirmed LIS or dICH from two tertiary hospitals between 2010 and 2021. We recorded vascular risk factors and SVD markers, including lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), and cerebral microbleeds (CMB). Logistic regression modeling was used to determine the association between vascular risk factors, SVD markers, and stroke phenotype. We further created WMH probability maps to compare WMH distribution between LIS and dICH.</p><p><strong>Results: </strong>A total of 834 patients with LIS (mean age 61.7 ± 12.1 years) and 405 with dICH (57.7 ± 13.2 years) were included. Hypertension was equally frequent between LIS and dICH (72.3% <i>versus</i> 74.8%, <i>p</i> = 0.349). Diabetes mellitus, hyperlipidemia, smoking, and prior ischemic stroke were more associated with LIS [odds ratio (OR) (95% confidence interval (CI)), 0.35 (0.25-0.48), 0.32 (0.22-0.44), 0.31 (0.22-0.44), and 0.38 (0.18-0.75)]. Alcohol intake and prior ICH were more associated with dICH [OR (95% CI), 2.34 (1.68-3.28), 2.53 (1.31-4.92)]. Lacunes were more prevalent in LIS [OR (95% CI) 0.23 (0.11-0.43)], while moderate-to-severe basal-ganglia PVS and CMB were more prevalent in dICH [OR (95% CI) 2.63 (1.35-5.27), 4.95 (2.71-9.42)]. WMH burden and spatial distribution did not differ between groups.</p><p><strong>Conclusion: </strong>The microangiopathy underlying LIS and dICH reflects distinct risk profiles and SVD features, hence possibly SVD subtype susceptibility. Prospective studies with careful phenotyping and genetics are needed to clarify the mechanisms underlying this difference.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241253901"},"PeriodicalIF":5.9,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11119384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium channel blockers and Parkinson's disease: a systematic review and meta-analysis.","authors":"Junyu Lin, Dejiang Pang, Chunyu Li, Ruwei Ou, Yujiao Yu, Yiyuan Cui, Jingxuan Huang, Huifang Shang","doi":"10.1177/17562864241252713","DOIUrl":"10.1177/17562864241252713","url":null,"abstract":"<p><strong>Background: </strong>The calcium channel has been considered to have great potential as a drug target for neuroprotective therapy in Parkinson's disease (PD), but previous studies yielded inconsistent results.</p><p><strong>Objectives: </strong>This study aimed to conduct a systematic review and meta-analysis to assess the relationship between using calcium channel blockers (CCBs) and the risk and progression of PD.</p><p><strong>Data sources and methods: </strong>The terms such as 'Parkinson's disease', 'PD', 'calcium channel blockers', and 'CCB' were used to search the literature published before 1 May 2023 in English databases, including PubMed, Embase, and Cochrane Library, for studies on CCB and PD. Data analysis was performed using Review Manager 5.3 software.</p><p><strong>Results: </strong>A total of 190 works of literature were preliminarily retrieved, and 177 works of literature were excluded by eliminating duplicates, reading abstracts, and reading full texts. A total of nine studies were finally included in the meta-analysis of the CCB and the risk of PD, and five studies were included in the systematic review of the CCB and the progression of PD. A total of 2,961,695 participants were included in the meta-analysis. The random-effects model was used for analysis due to significant heterogeneity. The main results of the meta-analysis showed that the use of CCB could reduce the risk of PD (relative risk 0.78, 95% confidence interval 0.62-0.99).</p><p><strong>Conclusion: </strong>CCB use was associated with a significantly reduced risk of PD. Whether CCB use has a disease-modifying effect on PD needs further study.</p><p><strong>Registration: </strong>PROSPERO: CRD42024508242.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241252713"},"PeriodicalIF":5.9,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11104025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and safety of telitacicept for refractory generalized myasthenia gravis: a retrospective study.","authors":"Jing Lin, Yue Li, Mengcui Gui, Bitao Bu, Zhijun Li","doi":"10.1177/17562864241251476","DOIUrl":"10.1177/17562864241251476","url":null,"abstract":"<p><strong>Background: </strong>Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein, holds promise for interrupting the immunopathology of this condition.</p><p><strong>Objectives: </strong>This study retrospectively assessed the effectiveness and safety of telitacicept in patients with refractory GMG.</p><p><strong>Design: </strong>A single-center retrospective study.</p><p><strong>Methods: </strong>Patients with refractory GMG receiving telitacicept (160 mg/week or biweekly) from January to September in 2023 were included. We assessed effectiveness using Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), myasthenia gravis treatment status and intensity (MGSTI), quantitative myasthenia gravis (QMG), and MG-activity of daily living (ADL) scores, alongside reductions in prednisone dosage at 3- and 6-month intervals. Safety profiles were also evaluated.</p><p><strong>Results: </strong>Sixteen patients with MGFA class II-V refractory GMG were included, with eight females and eight males. All patients were followed up for at least 3 months, and 11 patients reached 6 months follow-up. At the 3-month evaluation, 75% (12/16) demonstrated clinical improvement with MGFA-PIS. One patient achieved pharmacological remission, two attained minimal manifestation status, and nine showed functional improvement; three remained unchanged, and one deteriorated. By the 6-month visit, 90.1% (10/11) sustained significant symptomatic improvement. MGSTI scores and prednisone dosages significantly reduced at both follow-ups (<i>p</i> < 0.05). MG-ADL and QMG scores showed marked improvement at 6 months (<i>p</i> < 0.05). The treatment was well tolerated, with no severe adverse events such as allergy or infection reported.</p><p><strong>Conclusion: </strong>Our exploratory investigation suggests that telitacicept is a feasible and well-tolerated add-on therapy for refractory GMG, offering valuable clinical evidence for this novel treatment option.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241251476"},"PeriodicalIF":5.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to Guideline for the management of Myasthenic Syndromes. <i>Therapeutic Advances in Neurological Disorders</i>. Vol. 16(1): 1-31. DOI 10.1177/17562864231213240.","authors":"","doi":"10.1177/17562864241246400","DOIUrl":"https://doi.org/10.1177/17562864241246400","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/17562864231213240.].</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241246400"},"PeriodicalIF":5.9,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of systematic reviews comparing endovascular to best medical treatment for large-vessel occlusion acute ischaemic stroke: an umbrella review.","authors":"Apostolos Safouris, Lina Palaiodimou, Aristeidis H Katsanos, Odysseas Kargiotis, Konstantinos I Bougioukas, Klearchos Psychogios, Tatiana Sidiropoulou, Stavros Spiliopoulos, Marios-Nikos Psychogios, Georgios Magoufis, Guillaume Turc, Georgios Tsivgoulis","doi":"10.1177/17562864241246938","DOIUrl":"https://doi.org/10.1177/17562864241246938","url":null,"abstract":"<p><strong>Background: </strong>The literature on endovascular treatment (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) has been rapidly increasing after the publication of positive randomized-controlled clinical trials (RCTs) and a plethora of systematic reviews (SRs) showing benefit compared to best medical therapy (BMT) for LVO.</p><p><strong>Objectives: </strong>An overview of SRs (umbrella review) and meta-analysis of primary RCTs were performed to summarize the literature and present efficacy and safety of EVT.</p><p><strong>Design and methods: </strong>MEDLINE <i>via</i> Pubmed, Embase and Epistemonikos databases were searched from January 2015 until 15 October 2023. All SRs of RCTs comparing EVT to BMT were included. Quality was assessed using Risk of Bias in Systematic Reviews scores and the RoB 2 Cochrane Collaboration tool, as appropriate. GRADE approach was used to evaluate the strength of evidence. Data were presented according to the Preferred Reporting Items for Overviews of Reviews statement. The primary outcome was 3-month good functional outcome [modified Rankin scale (mRS) score 0-2].</p><p><strong>Results: </strong>Three eligible SRs and 4 additional RCTs were included in the overview, comprising a total of 24 RCTs, corresponding to 5968 AIS patients with LVO (3044 randomized to EVT <i>versus</i> 2924 patients randomized to BMT). High-quality evidence shows that EVT is associated with an increased likelihood of good functional outcome [risk ratio (RR) 1.78 (95% confidence interval (CI): 1.54-2.06); 166 more per 1000 patients], independent ambulation [mRS-scores 0-3; RR 1.50 (95% CI: 1.37-1.64); 174 more per 1000 patients], excellent functional outcome [mRS-scores 0-1; RR 1.90 (95% CI: 1.62-2.22); 118 more per 1000 patients] at 3 months. EVT was associated with reduced 3-month mortality [RR 0.81 (95% CI: 0.74-0.88); 61 less per 1000 patients] despite an increase in symptomatic intracranial haemorrhage [sICH; RR 1.65 (95% CI: 1.23-2.21); 22 more per 1000 patients].</p><p><strong>Conclusion: </strong>In patients with AIS due to LVO in the anterior or posterior circulation, within 24 h from symptom onset, EVT improves functional outcomes and increases the chance of survival despite increased sICH risk.</p><p><strong>Registration: </strong>PROSPERO Registration Number CRD42023461138.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241246938"},"PeriodicalIF":5.9,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The analysis of factors affecting medication adherence in patients with myasthenia gravis: a cross-sectional study.","authors":"Yining Su, Xinxian Wang, Yuemeng Xing, Zhenni Wang, Hailing Bu, Xiaoyan Cui, Yunying Yang, Bingxing Cai","doi":"10.1177/17562864231206877","DOIUrl":"https://doi.org/10.1177/17562864231206877","url":null,"abstract":"<p><strong>Background: </strong>Clinically, patients with myasthenia gravis are generally treated with drugs to improve their physical condition, and poor medication adherence can hinder their recovery. Many studies have shown the importance of medication adherence for effective treatment. Various factors may affect a patient's medication adherence; however, studies concerning medication adherence in patients with myasthenia gravis are rare.</p><p><strong>Objectives: </strong>This study aimed to identify the factors related to medication adherence in patients with myasthenia gravis, and determine the possibility of predicting medication adherence.</p><p><strong>Methods: </strong>This cross-sectional observational study was conducted among inpatients and outpatients with myasthenia gravis of the First Affiliated Hospital of Guangzhou University of Chinese Medicine in China. Data on patient demographics, disease-related characteristics, and medical treatment were collected. We evaluated medication adherence of the patients using the Morisky Medication Adherence Scale-8, Beliefs about Medicines Questionnaire, and the Self-efficacy for Appropriate Medication Use Scale.</p><p><strong>Results: </strong>We distributed 200 questionnaires and finally retrieved 198 valid questionnaires. A total of 139 (70.2%) women participated in this study, and 81 (40.9%) among the 198 participants were aged 40-59 years. In total, 103 (52.0%) participants exhibited bad adherence to pharmacological treatment, and factors such as taking medication irregularly [odds ratio (OR) = 0.242, 95% CI = 0.093-0.627], the necessity of taking medicine (OR = 1.286, 95% CI = 1.142-1.449), the concerns of taking medicine (OR = 0.890, 95% CI = 0.801-0.988), and the self-efficacy for taking medications under difficult circumstances (OR = 1.194, 95% CI = 1.026-1.389) had statistically significant impacts on medication adherence.</p><p><strong>Conclusion: </strong>Our study shows that taking medication irregularly and concerns of taking medicine are the risk factors for medication adherence. Meanwhile, the necessity of talking medicine and self-efficacy for taking medications under difficult circumstances are the protective factors for medication adherence. Our findings can help medical staff to enhance patients' medication adherence by informing patients necessary medical knowledge, emphasizing the necessity for medication, relieving patients' concerns regarding medication, and improving the self-efficacy for taking medications under difficult circumstances.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864231206877"},"PeriodicalIF":5.9,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study.","authors":"James F Howard, Saskia Bresch, Constantine Farmakidis, Miriam Freimer, Angela Genge, Channa Hewamadduma, John Hinton, Yessar Hussain, Raul Juntas-Morales, Henry J Kaminski, Angelina Maniaol, Renato Mantegazza, Masayuki Masuda, Richard J Nowak, Kumaraswamy Sivakumar, Marek Śmiłowski, Kimiaki Utsugisawa, Tuan Vu, Michael D Weiss, Małgorzata Zajda, Jos Bloemers, Babak Boroojerdi, Melissa Brock, Guillemette de la Borderie, Petra W Duda, Mark Vanderkelen, M Isabel Leite","doi":"10.1177/17562864241243186","DOIUrl":"https://doi.org/10.1177/17562864241243186","url":null,"abstract":"<p><strong>Background: </strong>Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments.</p><p><strong>Objectives: </strong>To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population.</p><p><strong>Design: </strong>Ongoing, multicenter, phase III open-label extension (OLE) study.</p><p><strong>Methods: </strong>Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score.</p><p><strong>Results: </strong>In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11-4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening (<i>n</i> = 52, 26%) and COVID-19 (<i>n</i> = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline -6.06 [-7.09, -5.03]) and were sustained through to Week 60 (-6.04 [-7.21, -4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (-6.46 [-8.19, -4.72]), and were sustained through to Week 60 (-6.51 [-8.37, -4.65]). Consistent results were observed in other efficacy endpoints.</p><p><strong>Conclusion: </strong>Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG population. Additional long-term data will be available in future analyses.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241243186"},"PeriodicalIF":5.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence, risk factors, and clinical outcomes of acute brain swelling associated with traumatic acute subdural hematoma: a retrospective study utilizing novel diagnostic criteria.","authors":"Shilong Fu, Haibing Liu, Guofeng Wang, Xiaofang Hu, Shousen Wang","doi":"10.1177/17562864241242944","DOIUrl":"https://doi.org/10.1177/17562864241242944","url":null,"abstract":"<p><strong>Background: </strong>Post-traumatic acute brain swelling (ABS) is a major cause of elevated intracranial pressure and thus mortality. The current definition of post-traumatic ABS has certain limitations, and there is limited information available regarding ABS associated with traumatic acute subdural hematoma (ASDH).</p><p><strong>Objectives: </strong>To investigate the incidence, risk factors, and clinical outcomes of ABS associated with traumatic ASDH.</p><p><strong>Design: </strong>Retrospective study.</p><p><strong>Methods: </strong>Data for 161 patients diagnosed with traumatic ASDH were retrospectively collected. Novel computed tomography-based criteria were proposed for diagnosing ABS in patients with ASDH and determining its incidence. Univariate and multivariate logistic regression analyses were performed to explore the risk factors of post-traumatic ABS. The Glasgow Outcome Scale (GOS) score, mortality, and functional prognosis of all patients at discharge and the proportion of intraoperative malignant brain bulge in surgical patients were taken as clinical outcome measures.</p><p><strong>Results: </strong>A total of 45 (28%) patients experienced post-traumatic ABS, exhibiting significantly lower Glasgow Coma Scale scores on admission (<i>p</i> < 0.001). The incidence of hemispheric and whole-brain swelling was 8.1% and 19.9%, respectively. Risk factors independently associated with post-traumatic ABS were: (1) age [odds ratio (OR) = 0.917, <i>p</i> < 0.001]; (2) platelet to white blood cell ratio (PWR) (OR = 0.887, <i>p</i> = 0.012); and (3) traumatic subarachnoid hemorrhage (SAH) (OR = 4.346, <i>p</i> = 0.005). The ABS cohort had a lower GOS score [2 (1-3) <i>versus</i> 4 (3-5); <i>p</i> < 0.001], higher mortality (46.7% <i>versus</i> 6.9%; <i>p</i> < 0.001), and higher proportion of unfavorable functional prognosis (75.6% <i>versus</i> 34.5%; <i>p</i> < 0.001) upon discharge compared to the no ABS cohort, along with higher proportion of intraoperative malignant brain bulge (43.8% <i>versus</i> 0%; <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>The incidence of ABS associated with ASDH is significantly high overall. Patients with ASDH who have young age, low PWR, and traumatic SAH are at an increased risk of developing post-traumatic ABS, and therefore of poor clinical outcomes.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241242944"},"PeriodicalIF":5.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of Bruton's tyrosine kinase inhibitors in multiple sclerosis.","authors":"Laura Airas, Robert A Bermel, Tanuja Chitnis, Hans-Peter Hartung, Jin Nakahara, Olaf Stuve, Mitzi J Williams, Bernd C Kieseier, Heinz Wiendl","doi":"10.1177/17562864241233041","DOIUrl":"https://doi.org/10.1177/17562864241233041","url":null,"abstract":"<p><p>Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation. B-cell depleting therapies have shown success as disease-modifying treatments (DMTs) in MS, highlighting the potential of BTK inhibitors for this indication; however, first-generation BTK inhibitors exhibit a challenging safety profile that is unsuitable for chronic use, as required for MS DMTs. A second generation of highly selective BTK inhibitors has shown efficacy in modulating MS-relevant mechanisms of pathogenesis in preclinical as well as clinical studies. Six of these BTK inhibitors are undergoing clinical development for MS, three of which are also under investigation for chronic spontaneous urticaria (CSU), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Phase II trials of selected BTK inhibitors for MS showed reductions in new gadolinium-enhancing lesions on magnetic resonance imaging scans; however, the safety profile is yet to be ascertained in chronic use. Understanding of the safety profile is developing by combining safety insights from the ongoing phase II and III trials of second-generation BTK inhibitors for MS, CSU, RA and SLE. This narrative review investigates the potential of BTK inhibitors as an MS DMT, the improved selectivity of second-generation inhibitors, comparative safety insights established thus far through clinical development programmes and proposed implications in female reproductive health and in long-term administration.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241233041"},"PeriodicalIF":5.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective observational study on characteristics, treatment patterns, and healthcare resource use of patients with myasthenia gravis in England.","authors":"Jordy van Enkhuizen, Jean Binns, April Betts, Fatemeh Saberi Hosnijeh, Myriam Alexander, Mark McCormack, Saiju Jacob","doi":"10.1177/17562864241237495","DOIUrl":"https://doi.org/10.1177/17562864241237495","url":null,"abstract":"<p><strong>Background: </strong>There are limited data on the real-world healthcare resource use (HCRU) and management costs of myasthenia gravis (MG) in England.</p><p><strong>Objective: </strong>This study aims to assess the burden of disease for patients with MG in England.</p><p><strong>Design: </strong>A retrospective, observational cohort study of adult patients diagnosed with MG, using data from the Hospital Episode Statistics data warehouse.</p><p><strong>Methods: </strong>Patients with a first-ever recorded diagnosis of MG between 30 June 2015 and 30 June 2020 were followed up until 30 June 2021 or death, whichever occurred first. Post-diagnosis patient characteristics, treatment patterns, HCRU, and costs were described. Costs were evaluated using National Health Service reference costs.</p><p><strong>Results: </strong>A total of 9087 patients with a median follow-up time of 2.9 years (range, 1.7-4.3 years) were included. The mean age at diagnosis was 66.5 years and 53% of the patients were male. A large proportion of patients (72.8%) were admitted as inpatients during follow-up with a mean number of 1.3 admissions. Patients hospitalized for MG-related complications spent a mean of 9.7 days per patient-year in the hospital. During follow-up, 599 (6.6% of the total cohort) and 163 (1.8%) patients had a record of rescue therapy with intravenous immunoglobulin (IVIg) and plasma exchange (PLEX), respectively. Rituximab was administered to 81 (0.9%) patients and 268 (2.9%) patients underwent thymectomy. In those patients receiving rescue therapy or rituximab, >10% received at least three cycles of the same treatment. The average annual cost of hospital admissions across all patients treated with IVIg, PLEX, and rituximab were £907,072, £689,979, and £146,726, respectively.</p><p><strong>Conclusion: </strong>A majority of MG patients required hospitalization or accident and emergency attendance, resulting in high HCRU and costs. A subset of patients required rescue therapy (including IVIg and PLEX), rituximab administration, ventilation, or thymectomy.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241237495"},"PeriodicalIF":5.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11022674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}