Therapeutic Advances in Neurological Disorders最新文献

{"title":"Eculizumab in thymoma-associated myasthenia gravis: a real-world cohort study.","authors":"Lei Jin, Dingxian He, Quantao Zeng, Song Tan, Jianquan Shi, Ying Liu, Zhangyu Zou, Jie Song, Chong Yan, Xiao Huan, Yuan Wang, Lei Yang, Jianying Xi, Zongtai Wu, Ziqi Liu, Jianming Zheng, Chongbo Zhao, Xianglin Chu, Sushan Luo","doi":"10.1177/17562864241309431","DOIUrl":"10.1177/17562864241309431","url":null,"abstract":"<p><strong>Background: </strong>Thymoma-associated myasthenia gravis (TAMG) is a subtype of myasthenia gravis (MG) that is associated with more severe symptoms and a relatively poor prognosis. Eculizumab, an inhibitor to target human C5 component of the complement cascade, is considered a treatment option for refractory generalized MG (gMG).</p><p><strong>Objectives: </strong>To explore the safety and efficacy of eculizumab in patients with TAMG.</p><p><strong>Design: </strong>This is an observational multicenter real-world cohort study to assess TAMG who were treated with eculizumab from June 2023 to June 2024.</p><p><strong>Data sources and methods: </strong>Clinical features associated with thymoma-associated multi-organ autoimmunity (TAMA), Myasthenia Gravis Activities of Daily Living (MG-ADL) score, and the incidence of treatment-emergent adverse events (TEAEs) were prospectively collected.</p><p><strong>Results: </strong>Overall, 42 patients with gMG were treated with eculizumab at 5 research centers, of whom 22 patients with TAMG were finally included. This cohort had a mean age of 51.5 ± 12.1 years and an average disease duration of 4.0 ± 4.3 years. Regarding thymomas, the World Health Organization (WHO) histological classification was primarily B2 and B3 (63.7%), and Masaoka staging was predominantly IV (45.5%). Nine participants (40.9%) switched from efgartigimod to eculizumab aiming at a better clinical improvement and reducing steroid use. By week 12, the MG-ADL score decreased to 4.8 ± 4.7 (baseline: 11.7 ± 6.0), and the corticosteroid dose reduced to 23.2 ± 26.5 mg (baseline: 41.8 ± 63.9 mg). Two patients with TAMA showed significant improvement in skin lesions and thrombocytopenia. Two TEAEs were recorded including COVID-19 and herpes labialis infection. Four patients (18.2%) died of respiratory or circulatory failure owing to thymoma metastasis.</p><p><strong>Conclusion: </strong>This real-world study demonstrates the efficacy of eculizumab in achieving symptom control and corticosteroid reduction for TAMG. It may also be a therapeutic option for refractory TAMG and TAMA.</p><p><strong>Trial registration: </strong>NCT04535843.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241309431"},"PeriodicalIF":4.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903484","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":"Complement inhibition in seropositive generalized myasthenia gravis as rescue therapy in impending and effective treatment in frequently recurring impending myasthenic crisis-a case series.","authors":"Martina Menacher, Monika Ellssel, Isabelle Kwiedor, Markus Naumann, Antonios Bayas","doi":"10.1177/17562864241301361","DOIUrl":"10.1177/17562864241301361","url":null,"abstract":"<p><p>In seropositive myasthenia gravis (MG), complement inhibition has been shown to be an effective and a fast-acting therapeutic option. Myasthenic crisis (MC), usually preceded by impending MC, is a life-threatening complication requiring highly effective treatments with rapid onset of action. Currently used treatment options of MC are limited, consisting mainly of symptomatic and immune therapies, that is, intravenous immunoglobulins and plasma exchange/immunoadsorption. So far, there is only very limited data on complement inhibitors in impending or manifest MC or termination of frequently recurring impending crises. Here, we report three cases of acetylcholine receptor antibody positive MG, two with impending and one case suffering from high-frequency impending MC, where complement inhibition with eculizumab or ravulizumab resulted in a rapid and sustained remission. Meningococcal vaccination, mandatory when using complement inhibitors, did not result in symptom-worsening or manifest MC.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241301361"},"PeriodicalIF":4.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903566","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":"Intrinsic brain activity differences in drug-resistant epilepsy and well-controlled epilepsy patients: an EEG microstate analysis.","authors":"Chaofeng Zhu, Jinying Zhang, Shenzhi Fang, Yuying Zhang, Juan Li, Luyan Wu, Huapin Huang, Wanhui Lin","doi":"10.1177/17562864241307846","DOIUrl":"10.1177/17562864241307846","url":null,"abstract":"<p><strong>Background: </strong>Drug-resistant epilepsy (DRE) patients exhibit aberrant large-scale brain networks.</p><p><strong>Objective: </strong>The purpose of investigation is to explore the differences in resting-state electroencephalogram (EEG) microstates between patients with DRE and well-controlled (W-C) epilepsy.</p><p><strong>Design: </strong>Retrospective study.</p><p><strong>Methods: </strong>Clinical data of epilepsy patients treated at the Epilepsy Center of Fujian Medical University Union Hospital from January 2020 to May 2023 were collected for a minimum follow-up period of 2 years. Participants meeting inclusion and exclusion criteria were categorized into two groups based on follow-up records: W-C group and DRE group. To ensure that the recorded EEG data were not influenced by medication, all EEG recordings were collected before patients commenced any antiepileptic drug treatment. Resting-state EEG datasets of all participants underwent microstate analysis. This study comprehensively compared the average duration, frequency per second, coverage, and transition probabilities (TPs) of each microstate between the two groups.</p><p><strong>Results: </strong>A total of 289 individuals who met the criteria were included, categorized into the W-C group (<i>n</i> = 112) and the DRE group (<i>n</i> = 177). EEG microstate analysis revealed substantial variances between the two groups. The analysis highlights differences in three of four microstate classifications. Microstate transition analysis demonstrated altered probabilities in DRE patients. Increased probabilities were observed in TP_AB, TP_BA, TP_BC, TP_CB, TP_BD, and TP_DB. Decreased probabilities included TP_CA, TP_DA, TP_AC, TP_AD, TP_CD, and TP_DC.</p><p><strong>Conclusion: </strong>This study highlights distinctive EEG microstate parameters and TPs in DRE patients compared to those with W-C epilepsy. The results may potentially advance the clinical application of EEG microstates.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241307846"},"PeriodicalIF":4.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903577","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":"First line treatment with subcutaneous efgartigimod in impending myasthenic crisis: a case report.","authors":"Isabelle Kwiedor, Martina Menacher, Monika Ellßel, Markus Naumann, Antonios Bayas","doi":"10.1177/17562864241307687","DOIUrl":"10.1177/17562864241307687","url":null,"abstract":"<p><p>In acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG), neonatal Fc-receptor (FcRn) inhibition has broadened the therapeutic spectrum. Myasthenic crisis (MC), heralded by an impending myasthenic crisis (iMC), is a critical condition requiring treatments with rapid onset and sustained efficacy. Currently treatments used for iMC, including intravenous immunoglobulins and plasma exchange/immunoadsorption, have limitations, such as delayed onset of action and potential side effects. So far, there is limited data on the use of FcRn inhibitors in the management of impending or manifest MC (mMC). Here, we present a case of AChR antibody-positive gMG with iMC, where subcutaneous administration of the FcRn inhibitor efgartigimod resulted in rapid clinical remission. Within 24 h of administration, the patient exhibited significant improvement in respiratory and bulbar muscle function, preventing progression to manifest MC and the need for mechanical ventilation. This rapid response was accompanied by a marked reduction in AChR antibody level by 89.8% within 4 weeks. This case supports the potential of efgartigimod as a fast-acting and effective treatment option for managing iMC, offering an alternative to existing therapies.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241307687"},"PeriodicalIF":4.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903575","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":"Chronic active lesions in multiple sclerosis: classification, terminology, and clinical significance.","authors":"Assunta Dal-Bianco, Jiwon Oh, Pascal Sati, Martina Absinta","doi":"10.1177/17562864241306684","DOIUrl":"10.1177/17562864241306684","url":null,"abstract":"<p><p>In multiple sclerosis (MS), increasing disability is considered to occur due to persistent, chronic inflammation trapped within the central nervous system (CNS). This condition, known as smoldering neuroinflammation, is present across the clinical spectrum of MS and is currently understood to be relatively resistant to treatment with existing disease-modifying therapies. Chronic active white matter lesions represent a key component of smoldering neuroinflammation. Initially characterized in autopsy specimens, multiple approaches to visualize chronic active lesions (CALs) in vivo using advanced neuroimaging techniques and postprocessing methods are rapidly emerging. Among these in vivo imaging correlates of CALs, paramagnetic rim lesions (PRLs) are defined by the presence of a perilesional rim formed by iron-laden microglia and macrophages, whereas slowly expanding lesions are identified based on linear, concentric lesion expansion over time. In recent years, several longitudinal studies have linked the occurrence of in vivo detected CALs to a more aggressive disease course. PRLs are highly specific to MS and therefore have recently been incorporated into the MS diagnostic criteria. They also have prognostic potential as biomarkers to identify patients at risk of early and severe disease progression. These developments could significantly affect MS care and the evaluation of new treatments. This review describes the latest knowledge on CAL biology and imaging and the relevance of CALs to the natural history of MS. In addition, we outline considerations for current and future in vivo biomarkers of CALs, emphasizing the need for validation, standardization, and automation in their assessment.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241306684"},"PeriodicalIF":4.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877852","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":"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":"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":"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}