Therapeutic Advances in Neurological Disorders最新文献

{"title":"Early infarct growth rate is associated with symptomatic intracranial hemorrhage after endovascular thrombectomy.","authors":"Wei Wang, Zhihang Huang, Shuaiyu Chen, Yan E, Jingwen Qi, Yi Xie, Mouxiao Su, Yingdong Zhang, Teng Jiang, Xiaohao Zhang","doi":"10.1177/17562864241306561","DOIUrl":"https://doi.org/10.1177/17562864241306561","url":null,"abstract":"<p><strong>Background: </strong>Time elapsed from stroke onset and baseline infarct volume is influential on endovascular thrombectomy (EVT) outcomes.</p><p><strong>Objectives: </strong>This study aimed to explore the utility of early infarct growth rate (EIGR) measured by apparent diffusion coefficient (ADC) in predicting symptomatic intracranial hemorrhage (sICH) of ischemic stroke patients after EVT.</p><p><strong>Methods: </strong>We retrospectively analyzed patients from the prospectively maintained stroke registry admitted between January 2019 and March 2023, presenting with large vessel occlusive stroke in the anterior circulation. EIGR was defined as ischemic core volume on magnetic resonance perfusion imaging (ADC ⩽620 × 10^-6 mm²/s) divided by the time from stroke onset to imaging. sICH was diagnosed according to the Heidelberg Bleeding Classification within 72 h after the procedure.</p><p><strong>Results: </strong>A total of 315 patients met the inclusion criteria. We observed sICH in 36 (11.4%) patients. After adjusting for the potential confounders, increased EIGR was confirmed to be independently associated with a higher risk of sICH (adjusted odds ratio, 1.033; 95% confidence interval (CI), 1.018-1.048; <i>p</i> = 0.001). Similar results were also confirmed when EIGR was analyzed as a categorical variable. Using a logistic regression model with restricted cubic splines, we found a linear correlation between EIGR and sICH risk (<i>p</i> = 0.001 for linearity). Furthermore, adding EIGR to a model containing conventional risk factors significantly improved risk reclassification for sICH (category-free net reclassification index, 0.393; 95% CI, 0.227-0.560; <i>p</i> = 0.001; integrated discrimination improvement, 0.245; 95% CI, 0.146-0.343; <i>p</i> = 0.001).</p><p><strong>Conclusion: </strong>Increased EIGR may predict the sICH in ischemic stroke patients who receiving EVT.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241306561"},"PeriodicalIF":4.7,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865428","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":"Efficacy and safety of tocilizumab treatment in refractory MOG-IgG related optic neuritis.","authors":"Xintong Xu, Yuhang Wang, Mingming Sun, Yuyu Li, Biyue Chen, Xiyun Chen, Quangang Xu, Shihui Wei, Huanfen Zhou","doi":"10.1177/17562864241306685","DOIUrl":"https://doi.org/10.1177/17562864241306685","url":null,"abstract":"<p><strong>Background: </strong>Myelin oligodendrocyte glycoprotein (MOG) IgG related optic neuritis (ON) which manifests as recurrent episodes and severe visual impairment remains a challenging issue in relapse prevention. Tocilizumab (TCZ), a human monoclonal antibody against IL-6R, may be an alternative treatment for the prevention of relapse in refractory MOG-ON patients.</p><p><strong>Objectives: </strong>To investigate the efficacy and safety of Tocilizumab (TCZ) in patients with recurrent myelin oligodendrocyte glycoprotein IgG related optic neuritis (MOG-ON).</p><p><strong>Design: </strong>We conducted an open-label, single-arm, nonrandomized, uncontrolled clinical trial at a tertiary neuro-ophthalmology center between April 1, 2021, and April 1, 2022.</p><p><strong>Methods: </strong>Participants with relapsed MOG-ON, whose disease had been resistant to previous immunotherapies, received tocilizumab as monotherapy or as an add-on therapy and were followed up for at least 12 months. Annual recurrence rate (ARR), best corrected visual acuity (BCVA), and adverse events were recorded for analyses.</p><p><strong>Result: </strong>Ten patients (7 females and 3 males) with relapsed MOG-ON were included with a mean (SD) ages of 28.6 (20.5) years old at disease onset and 30.9 (19.7) years at first TCZ administration, with a mean disease duration of 26.6 (11.3) months. Seven (70%) patients remained relapse-free, and the median (range) ARR dropped significantly from 1.9 (0.4-3.5) to 0.0 (0-4.0) during TCZ treatment (<i>p</i> = 0.006). Three patients experienced a relapse of ON at 2, 3, and 7 months after TCZ therapy. The median BCVA improved from 2.7 (2.0-3.0) logMAR at the nadir to 0.2 (0-2.0) logMAR at the last follow-up. Adverse effects included transient diarrhea (<i>n</i> = 1) and upper respiratory infection (<i>n</i> = 1).</p><p><strong>Conclusion: </strong>This study supports that Tocilizumab therapy, with or without concomitant immunosuppression, is safe and effective in reducing relapses in MOG-ON patients who have failed immunosuppressive therapy or targeted B-cell therapy.</p><p><strong>Trial registration: </strong>This trial is registered with the Chinese Clinical Trial Registry, number ChiCTR2100045273. (URL: https://www.chictr.org.cn/showproj.html?proj=124810).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241306685"},"PeriodicalIF":4.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847646","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":"Patient flow analysis with fast-track MRI for suspected stroke in the emergency department and associated non-comprehensive stroke center.","authors":"Malini Vendela Sagar, Karen Lind Gandrup, Diane Jensen, Christian Hedeager Krag, Mikael Ploug Boesen, Henriette Raaschou, Helle Collatz Christensen, Christina Kruuse","doi":"10.1177/17562864241303251","DOIUrl":"10.1177/17562864241303251","url":null,"abstract":"<p><strong>Background: </strong>Good outcomes in stroke care require swift diagnostics, for which magnetic resonance imaging (MRI) as first-line brain imaging is superior to computed tomography scans. Reduced length of stay (LOS) in hospital and emergency departments (ED) may optimize resource use. Fast-track stroke MRI was implemented as the primary imaging technique for suspected stroke, in the ED at Copenhagen University Hospital-Herlev and Gentofte in 2020.</p><p><strong>Objectives: </strong>We aimed to describe and compare LOS, MRI utilization, and the rate of strokes versus stroke-mimicking conditions on the stroke ward, before and after the implementation of fast-track MRI.</p><p><strong>Design and method: </strong>In this cross-sectional study, we used data from admissions to the neurologic ED and associated non-comprehensive stroke unit. We compared two time periods, that is, January 1-December 31, 2019, and January 1-December 31, 2020, before and after the implementation of fast-track stroke MRI.</p><p><strong>Results: </strong>There were 6650 admissions before and 7201 after implementation of fast-track stroke MRI. After implementation, we observed reductions in average LOS in hospitals from 56.0 to 38.6 h (<i>p</i> < 0.001), and LOS in ED from 9.17 to 8.63 h (<i>p</i> < 0.001). The use of inpatient MRI increased significantly, and the rate of acute ischemic stroke patients on the ward increased yet the rate of non-strokes remained unchanged. The association between shorter admissions and access to MRI remained (odds ratio 1.81, <i>p</i> < 0.001), after adjusting for sex, age, weekend admissions, and lockdown periods.</p><p><strong>Conclusion: </strong>Fast-track stroke MRI in ED associated with reduced LOS in hospital.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241303251"},"PeriodicalIF":4.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819190","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 rare association of Guillain-Barré syndrome/Miller-Fisher syndrome overlap syndrome and Herpes Simplex Virus Type 1 infection: trigger or exacerbating factor?","authors":"Claudia Alberti, Nicola Molitierno, Virginia Iacobelli, Daniele Velardo, Giacomo Pietro Comi, Stefania Corti, Mosè Parisi, Elena Abati","doi":"10.1177/17562864241297086","DOIUrl":"10.1177/17562864241297086","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) and its variants represent a spectrum of acute, immune-mediated polyneuropathies with heterogeneous clinical presentations and underlying etiologies. While infectious triggers are common precursors to these disorders, the association between viral infections and autoimmune neurological conditions remains an area of active investigation. Here, we report a case of GBS/Miller-Fisher syndrome overlap syndrome in an 80-year-old male presenting with dysarthria, dysphonia, ophthalmoplegia, areflexia, and postural instability following an upper respiratory tract infection. Cerebrospinal fluid analysis revealed the unexpected detection of herpes simplex virus type 1 DNA. Treatment with intravenous immunoglobulin therapy and acyclovir resulted in a progressive recovery of neurological symptoms. This case emphasizes the role of viral infections in differential diagnosis or as potential triggers for autoimmune neurological disorders highlighting the efficacy to addressed therapy in such complex cases.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241297086"},"PeriodicalIF":4.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772690","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":"Clinical and radiological implications of subpotent generic fingolimod in multiple sclerosis: a case series.","authors":"Darin T Okuda, Lauren M Tardo, Crystal M Wright, Shanan B Munoz, Tom G Punnen, Mahi A Patel, Tatum M Moog, Katy W Burgess","doi":"10.1177/17562864241300047","DOIUrl":"10.1177/17562864241300047","url":null,"abstract":"<p><p>An expansion in the availability of generic specialty disease modifying therapies (DMTs) for treatment of multiple sclerosis (MS) has increased recently. Generic specialty medications aim to provide greater access to molecules that alter the disease trajectory at lower costs. The US Food and Drug Administration requires generic products to contain between 90% and 110% of the stated active ingredient and an 80%-125% bioequivalence range. We present the clinical experiences and absolute lymphocyte counts (ALC) trends of six people with MS originally treated with Gilenya^® (fingolimod) 0.5 mg who were required to transition to generic fingolimod 0.5 mg by third-party administrators, and the medication content from recovered products. Six individuals with acute clinical exacerbations or disease advancement on MRI were identified during routine scheduled visits from a tertiary care center and consecutively included from January 2024 to August 2024. ALC trends were constructed for each individual during Gilenya^® and generic fingolimod treatment. These individuals experienced signs of disease advancement while on generic fingolimod 0.5 mg at approximately 1 year of treatment and elevations in ALC, a biological metric related to the mechanism of action of sphingsine-1-phosphate receptor modulation, were observed following the transition. High purity fingolimod for standardization tests, Gilenya^® 0.5 mg, and five recovered generic fingolimod 0.5 mg products were independently tested in an accredited laboratory. Gilenya^® 0.5 mg capsules had an average fingolimod content of 97.7% (standard deviation (SD) = 2.59%). Three recovered generic fingolimod 0.5 mg products used during relapses had an average content of 91.2% (3.25%), 81.6% (6.24%), and 72.5% (2.05%). Two generic fingolimod 0.5 mg products not associated with relapse activity revealed averages of 97.4% (1.82%) and 103.3% (3.77%). Subpotent generic specialty DMTs may not only result in greater risk for disease activity but may also expose individuals to the potential for disease rebound, depending on the mechanism of action.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241300047"},"PeriodicalIF":4.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688954","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":"Short delay to initiate plasma exchange or immunoadsorption as synergistic therapies for patients in the acute phase of anti-NMDAR encephalitis.","authors":"Miao Su, Zichao Wu, Qiuyan Luo, Huiyu Feng, Hongyan Zhou","doi":"10.1177/17562864241276208","DOIUrl":"10.1177/17562864241276208","url":null,"abstract":"<p><strong>Background: </strong>Combined first-line therapies have been frequently adopted for patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Plasma exchange (PE) or immunoadsorption (IA) was used as an add-on option following initial immunotherapies, including high-dose steroids and intravenous immunoglobulin (IVIG). However, whether a shorter delay of PE or IA can improve the early recovery prognosis of patients with anti-NMDAR encephalitis remains largely unknown.</p><p><strong>Objective: </strong>To compare short-term clinical improvement between patients with early and late initiation of PE or IA in anti-NMDAR encephalitis.</p><p><strong>Design: </strong>A retrospective study was conducted for patients admitted with anti-NMDAR encephalitis between January 2015 and December 2023 (<i>n</i> = 29), including 21 patients who received PE or IA as synergistic therapies.</p><p><strong>Methods: </strong>The clinical prognosis was compared between the early PE/IA group and the late PE/IA group in the research. Primary outcome included changes in the Clinical Assessment Scale for Autoimmune Encephalitis (∆CASE) at 90 and 120 days after encephalitis onset. Secondary outcomes included changes in the modified Rankin scale (∆mRS) after 90 and 120 days from encephalitis onset, and the length of intensive care unit (ICU) stay for patients with severe anti-NMDAR encephalitis.</p><p><strong>Results: </strong>The ∆CASE scores after 90 and 120 days from encephalitis onset revealed a significant difference between patients with early and late initiation of PE or IA (<i>p</i> ⩽ 0.05). A significant difference in the ∆mRS was also found between patients with early and late initiation of PE or IA in severe encephalitis (<i>p</i> ⩽ 0.05). No significant difference was found in the length of ICU admission (<i>p</i> = 0.101).</p><p><strong>Conclusion: </strong>Our findings emphasize the importance of considering PE or IA as early as feasible for patients with anti-NMDAR encephalitis, even when steroids and IVIG are in use.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241276208"},"PeriodicalIF":4.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628908","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":"Bacterial signature in retrieved thrombi of patients with acute ischemic stroke-a systematic review.","authors":"Armin Zarrintan, Sherief Ghozy, Kasthuri Thirupathi, Kalah Walden, Waleed Brinjikji, David F Kallmes, Ramanathan Kadirvel","doi":"10.1177/17562864241296713","DOIUrl":"https://doi.org/10.1177/17562864241296713","url":null,"abstract":"<p><strong>Background: </strong>Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS.</p><p><strong>Objectives: </strong>We aim to systematically review all studies that have investigated the presence of bacterial signatures within thrombi retrieved following mechanical thrombectomy (MT) procedures in patients with AIS.</p><p><strong>Design: </strong>This systematic review is designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist.</p><p><strong>Data sources and methods: </strong>A comprehensive search was conducted in the Web of Sciences, PubMed, Scopus, and Embase databases to identify relevant studies.</p><p><strong>Results: </strong>The literature search and screening included 11 studies involving 674 patients, with 414 (61.4%) being male and 260 (38.6%) females. Among all the patients, 393 (58.3%) were positive for bacterial presence in their retrieved thrombi. The most utilized technique for bacterial signature detection was bacterial DNA extraction followed by polymerase chain reaction amplification of the 16S rRNA gene sequence. <i>Staphylococcus aureus</i> was the most studied bacteria among the studies analyzed.</p><p><strong>Conclusion: </strong>Bacterial infections and the presence of bacteria within thrombi may significantly contribute to AIS by initiating or exacerbating atherosclerosis or thrombosis. Understanding the mechanisms by which bacteria affect vascular health is crucial for developing effective preventive and therapeutic strategies for stroke patients.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241296713"},"PeriodicalIF":4.7,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628869","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 impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study.","authors":"David Levitz, Yi Chao Foong, Paul Sanfilippo, Tim Spelman, Louise Rath, Angie Roldan, Anoushka Lal, Mastura Monif, Vilija Jokubaitis, Serkan Ozakbas, Raed Alroughani, Cavit Boz, Murat Terzi, Tomas Kalincik, Yolanda Blanco, Matteo Foschi, Andrea Surcinelli, Katherine Buzzard, Olga Skibina, Guy Laureys, Liesbeth Van Hijfte, Cristina Ramo-Tello, Aysun Soysal, Jose Luis Sanchez-Menoyo, Mario Habek, Elisabetta Cartechini, Juan Ignacio Rojas, Rana Karabudak, Barbara Willekens, Talal Al-Harbi, Yara Fragoso, Tamara Castillo-Triviño, Danny Decoo, Maria Cecilia Aragon de Vecino, Eli Skromne, Carmen-Adella Sirbu, Chao Zhu, Daniel Merlo, Melissa Gresle, Helmut Butzkueven, Anneke Van Der Walt","doi":"10.1177/17562864241278496","DOIUrl":"https://doi.org/10.1177/17562864241278496","url":null,"abstract":"<p><strong>Background: </strong>The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort.</p><p><strong>Objective: </strong>To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort.</p><p><strong>Design: </strong>This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years.</p><p><strong>Methods: </strong>Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed.</p><p><strong>Results: </strong>The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09-0.11]) compared to controls (ARR = 0.07 [95% CI 0.06-0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29-1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92-1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25-2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06-3.90]) compared to patients on BRACE therapy without COVID-19 infection.</p><p><strong>Conclusion: </strong>COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241278496"},"PeriodicalIF":4.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628952","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":"SCALA: a randomized phase I trial comparing subcutaneous and intravenous alemtuzumab in patients with progressive multiple sclerosis.","authors":"Xavier Montalban, Breogan Rodriguez-Acevedo, Carlos Nos, Mireia Resina, Mireia Forner, Yanzhen Wu, Magdalena Chirieac","doi":"10.1177/17562864241291655","DOIUrl":"https://doi.org/10.1177/17562864241291655","url":null,"abstract":"<p><strong>Background: </strong>Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment.</p><p><strong>Objectives: </strong>We sought to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of SC-administered alemtuzumab in people with progressive multiple sclerosis (PMS).</p><p><strong>Design: </strong>SCALA was a phase I, open-label, randomized, parallel-group study with two 12-month periods and a safety monitoring phase to 60 months.</p><p><strong>Methods: </strong>Of 29 screened participants, 24 were enrolled and randomized 2:1 to two 12 mg/day alemtuzumab treatments (60 and 36 mg total; SC:IV). Key inclusion criteria: ⩾18 years with a PMS diagnosis. Key exclusion criteria included RRMS diagnosis and prior treatment with anti-CD52 antibodies. Primary endpoint: CD3⁺ lymphocyte count. Secondary endpoints: PD and PK parameters.</p><p><strong>Results: </strong>Demographics were broadly similar for participants in the SC (16) and IV (8) arms; more participants with primary PMS received SC (44%) versus IV (25%) treatment. After the first course, the mean CD3⁺ cell count/µL was reduced at month 1 in both arms (SC: baseline (BL) 1326 to 48 vs IV: BL 1155 to 84). Lymphocyte counts partially repopulated by month 12, with mean CD3⁺ cell counts/µL of SC 599 versus IV 528. The mean lymphocyte counts/µL decreased again after the second course at month 13 in both arms (SC: 90 vs IV: 129), with partial repopulation by month 24. Alemtuzumab serum concentrations were lower following SC administration relative to IV, with 32% bioavailability. There were no adverse events leading to permanent treatment discontinuation or death.</p><p><strong>Conclusion: </strong>In SCALA, there were similar patterns of lymphocyte depletion and repopulation for participants receiving SC or IV alemtuzumab. In both arms, alemtuzumab had a manageable safety profile, with no emerging safety concerns. The general stabilization of neurological outcomes observed over 60 months underscores the potential long-term benefits of alemtuzumab treatment.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov identifier: NCT02583594.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241291655"},"PeriodicalIF":4.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605310","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":"Identification of alemtuzumab-suitable multiple sclerosis patients in Slovakia and sequencing of post-alemtuzumab immunomodulatory treatment.","authors":"Ema Kantorová, Marianna Vítková, Martina Martiníková, Andrea Cimprichová, Miriam Fedicˇová, Slavomíra Kovácˇová, Miroslav Mako, Juraj Cisár, Viera Hancˇinová, Jarmila Szilasiová, Peter Koleda, Jana RoháIˇová, Jana Polóniová, Martin Karlík, Darina Slezáková, Eleonóra Klímová, Matúš Maciak, Egon Kurcˇa, Petra Hnilicová","doi":"10.1177/17562864241285556","DOIUrl":"10.1177/17562864241285556","url":null,"abstract":"<p><strong>Background: </strong>Alemtuzumab (ALEM) is a humanised monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, which is expressed in high levels on T- and B-lymphocytes. This depletion is followed by lymphocyte repopulation and a cytokine expression shift towards a lesser inflammatory profile, both of which may contribute to prolonged efficacy. National recommendations for enrolling and treating multiple sclerosis (MS) patients with ALEM have been established. However, there are no recommendations in place for the treatment of MS reactivation after the ALEM treatment.</p><p><strong>Objectives: </strong>To evaluate the effectiveness and safety of the use of ALEM and to analyse subsequent disease-modifying treatments (DMTs). A multidimensional prediction model was developed to make a patient-specific prognosis regarding the response to ALEM.</p><p><strong>Design: </strong>A multicentre, prospective, non-controlled, non-interventional, observational cohort study.</p><p><strong>Methods: </strong>Relapsing multiple sclerosis patients (RMSp) who received ⩾1 dose of ALEM were enrolled. In each treatment year, the following baseline and prospective data were collected: age, MS history, number, type and duration of previous disease-modifying treatment (PDMT), relapse rate (REL), expanded disability status scale (EDSS), magnetic resonance imaging and serious adverse events (AE). In cases of reactivation of MS, all data about the subsequent DMT were collected.</p><p><strong>Results: </strong>A total of 142 RMSp from 10 MS Slovak Centres fulfilled the inclusion criteria. The average age was 35 years (standard error 8.56). The overall average EDSS was 3.87 (1.46) when ALEM was started. The average duration of PDMT was 6.0 (4.04) years, and the median number of PDMTs was 3 (0-5), while the patients were mostly treated with 2 or 3 DMTs (>65.00%). Post-ALEM treatment was needed in 39 cases (27.46%). The most frequent post-ALEM treatment indicated was ocrelizumab, followed by natalizumab (NAT), siponimod and cladribine. The ocrelizumab and NAT treatment bring little benefit to patients. Siponimod showed less EDSS increase in contrast to ocrelizumab and NAT. Another repopulation therapy, cladribine, may also be an effective option. Statistically significant predictors for the expected EDSS are age (<i>p</i>-value <0.0001), number of ALEM cycles (0.0066), high number of PDMT (0.0459) and the occurrence of relapses (<0.0001). There was no statistically significant effect on the patient's gender (0.6038), duration of disease-modifying treatment before alemtuzumab (0.4466), or the occurrence of AE (0.6668).</p><p><strong>Conclusion: </strong>The study confirms the positive effect of ALEM on clinical and radiological outcomes. We need more data from long-term sequencing studies.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241285556"},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569645","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}