Neurology and Therapy最新文献

{"title":"Dysphagia Management is Associated with Reduced Mortality in Patients with Moderate to Severe Acute Ischemic Stroke.","authors":"Julian Frederic Hotz, Lisa Kaindl, Lisa Schneider, Stefan Krebs, Anel Karisik, Dominika Mikšová, Maximilian Bichler, Lavinia Ritscher, Moritz Staudacher, Heimo Lagler, Heinz Burgmann, Wilfried Lang, Julia Ferrari, Michael Knoflach, Marek Sykora","doi":"10.1007/s40120-025-00783-1","DOIUrl":"https://doi.org/10.1007/s40120-025-00783-1","url":null,"abstract":"<p><strong>Introduction: </strong>Dysphagia and pneumonia are common complications in patients with acute ischemic stroke (AIS), contributing to increased morbidity and mortality. This study evaluated the impact of pneumonia and dysphagia management strategies (including dysphagia screening, speech therapy, and nasogastric tube use) on patients with AIS outcomes.</p><p><strong>Methods: </strong>This nationwide, multicenter study included 181,704 patients with AIS from the Austrian Stroke Unit Registry (2006-2024). The impact of pneumonia and the influence of dysphagia management on favorable functional outcome (modified Rankin Scale ≤ 1) and mortality of patients with AIS were calculated using multivariable Poisson regression models.</p><p><strong>Results: </strong>Pneumonia occurred in 15.7% of severely and in 6.7% of moderately affected patients with AIS and was associated with increased mortality (RR 1.61, 95% CI 1.50-1.72, p < 0.05) and inversely with favorable functional outcome (RR 0.37, 95% CI 0.31-0.44, p < 0.05). Dysphagia management was significantly (p < 0.05) associated with reduced mortality, especially in moderately to severely affected patients with AIS, but had a limited impact on functional outcome. After implementation of dysphagia screening, a significant (p < 0.05) decrease in pneumonia prevalence was noted.</p><p><strong>Conclusion: </strong>Among patients with severe acute ischemic stroke, early dysphagia management strategies are associated with reduced mortality, while stroke-associated pneumonia remains a persistent predictor of poor prognosis. These findings underscore the important role of standardized dysphagia management in improving stroke care and patient outcomes.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Patient-centric Clinical Trial Design to Comprehensively Evaluate Low-Sodium Oxybate in People with Idiopathic Hypersomnia or Narcolepsy.","authors":"Deborah A Nichols, Teresa L Steininger, Douglas S Fuller, M Todd Kirby, Emily C Barker, Marisa Whalen, Jessica K Alexander, Sarah Akerman, David T Plante","doi":"10.1007/s40120-025-00745-7","DOIUrl":"https://doi.org/10.1007/s40120-025-00745-7","url":null,"abstract":"<p><strong>Introduction: </strong>Low-sodium oxybate (LXB; Xywav^®) is approved to treat idiopathic hypersomnia in adults and excessive daytime sleepiness or cataplexy in individuals aged ≥ 7 years with narcolepsy. The efficacy and safety of LXB have been demonstrated in randomized controlled trials. This study will comprehensively evaluate multiple daytime and nighttime symptoms in participants with idiopathic hypersomnia and participants with narcolepsy treated with LXB.</p><p><strong>Methods: </strong>Jazz DUET (Develop hypersomnia Understanding by Evaluating low-sodium oxybate Treatment; NCT05875974) is a prospective, multi-cohort, multicenter, single-arm, open-label, interventional study. Establishing multiple cohorts across different diseases aligns with more generalizable research designs enabling a broader impact. Total study duration is ~ 10-21 weeks, which includes a 2- to 6-week screening period, an 8-day baseline period, a 2- to 8-week titration period, a 2-week stable-dose period, a 1- to 2-week end-of-treatment assessment period, and a 2-week safety follow-up period. To provide a robust dataset of changes with LXB treatment which will inform healthcare providers and their patients, DUET is administering a wide range of patient- and clinician-reported outcome assessments regarding symptom severity and daytime functioning and includes objective measures of sleep (ad libitum polysomnography protocol) and sleep inertia which have not been previously tested with this type of study design. Additionally, pharmacokinetics data and clinician titration feedback are collected to inform titration/dosing guidance for clinicians. DUET was designed in a patient-centric manner to reflect a real-world approach to conducting clinical trials.</p><p><strong>Planned outcomes: </strong>Using a patient-centric design aiming to address participants' burden and improve their study experience, the DUET study will fill critical idiopathic hypersomnia and narcolepsy evidence gaps pertaining to sleep architecture (e.g., disrupted nighttime sleep) and response to LXB treatment, as well as provide data on outcomes that are meaningful to patients. Graphical abstract available for this article.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Endovascular Treatment in Patients with Large Vessel Occlusion Stroke of Different Mechanisms.","authors":"Zhiyuan Feng, Ming Yang, Aoming Jin, Ning Ma, Feng Gao, Dapeng Mo, Xiaojuan Liu, Fangyuan Zhang, Xinchen Li, Yimeng Li, Qi Chu, Jing Xue, Aichun Cheng, Jinxi Lin, Hao Li, Xia Meng, Zhongrong Miao, Yongjun Wang, Jie Xu","doi":"10.1007/s40120-025-00776-0","DOIUrl":"https://doi.org/10.1007/s40120-025-00776-0","url":null,"abstract":"","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perampanel as Add-on in Patients Aged ≥ 12 Years with Focal Epilepsy: A Prospective Real-World Observational Study from Southern China.","authors":"Xiaoli Shi, Xiangru Lu, Lixia Li, Yanting Lu, Lang Shen, Jinou Zheng, Yuan Wu, Lu Yu","doi":"10.1007/s40120-025-00760-8","DOIUrl":"https://doi.org/10.1007/s40120-025-00760-8","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to evaluate the effectiveness, tolerability and safety of perampanel (PER) as an add-on therapy for southern Chinese patients aged ≥ 12 years with focal epilepsy.</p><p><strong>Methods: </strong>This prospective cohort study enrolled consecutive patients with focal epilepsy treated between January 2023 and January 2024. Patients received PER as add-on therapy, with medication adjustments, seizure frequency and adverse events (AEs) monitored at 3, 6, 9 and 12 months. Logistic regression analyzed factors influencing 6- and 12-month treatment outcomes.</p><p><strong>Results: </strong>Among 196 patients (full analysis set), 169 (86.2%) had drug-resistant epilepsy. Of these, 73.5% (144/196) received PER ≤ 4 mg/day. The 50% response rates at 6 and 12 months were 79.7% (114/143) and 86.0% (86/100), respectively. Retention rates at 6 and 12 months were 78.3% (148/189) and 59.3% (102/172), with cumulative retention rates of 71.8% and 63.3%, respectively. AEs occurred in 42 patients (21.4%), primarily dizziness and psychiatric symptoms. Logistic regression analysis identified disease duration of < 5 years (OR = 15.893, 95% CI = 1.418-178.158, P < 0.05) and unknown etiology (OR = 14.528, 95% CI = 2.508-84.140, P < 0.05) as predictors of higher long-term response rates.</p><p><strong>Conclusion: </strong>PER demonstrated good effectiveness and safety as an add-on therapy for focal epilepsy in southern Chinese patients aged ≥ 12 years. Lower doses of PER (≤ 4 mg/day) may achieve satisfactory effectiveness in PER-sensitive populations, while shorter disease duration and unknown etiology were associated with better long-term outcomes. These findings support PER's utility in managing focal epilepsy, particularly in drug-resistant cases.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Spectrum of Acquired Demyelinating Syndromes in Children: A Tertiary Hospital Experience.","authors":"Mohammed Almuqbil, Lama Aljomah, Nora Almahmoud, Waleed Altuwaijri, Ahmad Alrumayyan, Muhammad T Alrifai","doi":"10.1007/s40120-025-00768-0","DOIUrl":"https://doi.org/10.1007/s40120-025-00768-0","url":null,"abstract":"<p><strong>Introduction: </strong>Although acquired demyelinating syndromes (ADS) are rare in children, the incidence and prevalence of ADS vary internationally. As data on pediatric ADS in Saudi Arabia is limited, the aim of this study was to describe the clinical spectrum of pediatric ADS, its clinical characteristics, and management options at a tertiary hospital in Saudi Arabia.</p><p><strong>Methods: </strong>A retrospective observational study was conducted at King Abdulaziz Medical City (KAMC) and King Abdullah Specialized Children Hospital (KASCH) in Riyadh, Saudi Arabia between January 2016 and December 2022. All patients with ADS fulfilling criteria of each subtype (multiple sclerosis (MS), clinically isolated syndrome (CIS), acute disseminated encephalomyelitis (ADEM), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)) were included in this study.</p><p><strong>Results: </strong>Forty-five pediatric patients with ADS were analyzed, with the majority diagnosed with MS. The median age of onset was higher in the MS group compared to monophasic CIS and MOGAD, with statistically significant differences in age at onset between the MS group and both the CIS and MOGAD groups (p = 0.0002). Significant differences were also observed in the type of initial central nervous system (CNS) attack, with optic neuritis being more common in MS and transverse myelitis in CIS (p < 0.0001). Laboratory results revealed a higher incidence of cerebrospinal fluid (CSF) oligoclonal bands in patients with MS, which was statistically significant (p =  0.04), and MOG antibodies were found in all patients with MOGAD. Intravenous pulse steroids were administered in most patients, while disease-modifying drugs (DMTs) were employed most frequently in patients with MS. The Expanded Disability Status Scale scores indicated little disability in most patients with MS and CIS, with more disability noted in a subgroup of ADEM. Overall, the study underscores the clinical heterogeneity of pediatric ADS and points out the statistically significant difference in age at onset, presenting features, and laboratory findings among ADS subtypes.</p><p><strong>Conclusions: </strong>This study provides a thorough overview of pediatric ADS, including important distinctions between MS, ADEM, CIS, and MOGAD. Marked differences in age at onset, presentation, and imaging among these subtypes are informative for maximizing diagnosis and treatment. The key findings are the subsequent development of MS from CIS and MOGAD, varying patterns of first attack, and imaging characteristics like callososeptal interface lesions in MS and posterior fossa hyperintensities in MOGAD. All these indicate the need for individualized diagnostic and therapeutic approaches for improved outcomes.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Consequences of Cladribine Tablets for the Treatment of Highly Active Relapsing-Remitting Multiple Sclerosis in Italy.","authors":"Barbara Polistena, Anna Maria Provenzano, Caterina Rizzi, Elena Colombo, Roberto Bergamaschi","doi":"10.1007/s40120-025-00761-7","DOIUrl":"https://doi.org/10.1007/s40120-025-00761-7","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a chronic autoimmune disease impacting the central nervous system. Individuals with highly active relapsing-remitting MS (HA-RRMS) frequently experience symptomatic episodes lasting more than 24 h, followed by a remission period completely or partially symptom free. This study aimed to assess the economic impact of cladribine tablets for the treatment of patients with HA-RRMS in the Italian context.</p><p><strong>Methods: </strong>A Markov model developed by PRECISIONheor for simulating treatment outcomes in patients with HA-RRMS aged over 18 years over three treatment lines was adapted to the Italian National Health System organization. The model considers direct costs of treatment and relapse management, as well as costs related to adverse events and indirect costs. The model adopts the societal perspective and a 4-year time horizon. Uncertainty was addressed through deterministic sensitivity analysis.</p><p><strong>Results: </strong>The analysis considered 16,691 out of 55,635 Italian patients with HA-RRMS (30%). Treatment with cladribine tablets extended the duration of patients' responsive stage (relapse free) from 1.3 months (worst scenario) to 1.4 months (best scenario) when compared to oral disease-modifying therapies (DMTs) and from 2.4 to 5.7 months when compared to monoclonal antibody DMTs. cladribine tablets were associated with cost savings ranging from 69.9% to 10.9% compared to oral DMTs and from 74.3% to 33.0% compared to monoclonal antibody DMTs. The cost savings per additional month in responsive stage ranged from € 27,663.2 to € 4154.3 vs oral DMTs and from € 16,224.5 to € 3035.3 vs monoclonal antibody DMTs.</p><p><strong>Conclusion: </strong>Cladribine tablets are associated with a benefit in terms of prolonging the non-relapsing phase in patients with HA-RRMS, as well as substantial direct cost savings in comparison with all other DMTs. Our analysis suggests that adopting cladribine tablets for HA-RRMS enables clinical benefits over a 4-year time horizon and savings for Italian society.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, Humanistic, and Economic Value of 'Good ON-Time' in Advanced Parkinson's Disease: A Multinational Real-World Study.","authors":"Joohi Jimenez-Shahed, Irene A Malaty, Jean-Philippe Azulay, Ashwini Parab, Connie H Yan, Prasanna L Kandukuri, Pavnit Kukreja, Jorge Zamudio, Alexander Gillespie, Angelo Antonini","doi":"10.1007/s40120-025-00765-3","DOIUrl":"https://doi.org/10.1007/s40120-025-00765-3","url":null,"abstract":"<p><strong>Introduction: </strong>In advanced Parkinson's disease (aPD), 'ON-time' indicates periods of better symptom control, with 'good ON-time (GOT)' indicating control without troublesome dyskinesia. Despite its importance, the impact of increased 'GOT' on aPD outcomes is understudied. This study aims to evaluate the clinical, humanistic, and economic value of incremental hourly increases in 'GOT' for people with aPD.</p><p><strong>Methods: </strong>The study analyzed data from people with aPD across seven countries, using the Adelphi Parkinson's Disease Specific Program survey (2017-2020). 'GOT' (calculated from self-reported ON/OFF-time and the proportion of troublesome dyskinesia time) was normalized to a 16-h day. Outcomes included symptom control, medication use, falls, activities of daily living (ADLs), quality of life (QoL), and healthcare resource utilization (HRU). Regression models evaluated relationships between incremental 'GOT' hours and outcomes.</p><p><strong>Results: </strong>Of 802 patients (mean [standard deviation; SD] age, 76.1 [8.9] years; male, 60.3%) included in the analysis, mean (SD) 'GOT' was 13.1 (2.7) hours/day. Hourly increases in 'GOT' were associated with lower likelihood of reporting uncontrolled motor (odds ratio [OR] 0.79; 95% confidence interval (CI) [0.62, 1.01]) and non-motor symptoms (OR 0.88; 95% CI [0.80, 0.96]), taking ≥ 2 PD medication classes (OR 0.91; 95% CI [0.86, 0.97]) and lower fall risk (incidence rate ratio 0.91; 95% CI [0.87, 0.95]). Hourly increases in 'GOT' were significantly associated with reduced humanistic burden (greater ADL independence, OR 1.19; 95% CI [1.04 1.37]) and improved QoL (for Parkinson's Disease Questionnaire [PDQ]-39: coefficient - 1.49; 95% CI [- 2.46, - 0.52]) and with reduced economic burden, with annual total HRU cost-savings of $8602.24 (95% CI - $12,192.70 to $5011.77).</p><p><strong>Conclusions: </strong>In this multi-country, real-world study of people with aPD, hourly increases in 'GOT' were associated with improved clinical outcomes, greater humanistic value, and reduced economic burden. Interventions that maximize improvement of 'GOT' should be considered for people with aPD adequately controlled on current therapy.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations.","authors":"Susan Perlman, Mathieu Anheim, Sylvia Boesch, James H Lewis, David R Lynch","doi":"10.1007/s40120-025-00752-8","DOIUrl":"https://doi.org/10.1007/s40120-025-00752-8","url":null,"abstract":"<p><p>Omaveloxolone is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥ 16 years and is under clinical development for pediatric patients. In the MOXIe study, alanine and aspartate aminotransferase (ALT and AST) elevations were among the most common treatment-emergent adverse events (TEAEs) in the omaveloxolone arm and were mild to moderate, generally asymptomatic, transient, and reversible; no patients who received omaveloxolone had laboratory abnormalities that met the Hy's law criteria. Omaveloxolone labels (US and EU) provide guidance for monitoring and managing these elevations. Here, practical use considerations, from experience-based opinions of four FA experts and a hepatologist via semi-structured interviews, are presented. Prior to omaveloxolone initiation, assessment of baseline ALT, AST, and total bilirubin is recommended per label. During treatment, ALT, AST, and total bilirubin should be monitored monthly for the first 3 months and periodically thereafter per label. Reduced frequency of patient monitoring after 3 months is suggested if aminotransferase levels remain normal. Per label, omaveloxolone should be temporarily discontinued if aminotransferases increase to > 5 × the upper limit of normal (ULN) or > 3 × ULN with other evidence of liver dysfunction. Stemming from real-world practical considerations wherein patients are followed up less frequently than in the trial setting, treatment interruption when aminotransferases increase to ≥ 3 × ULN without other signs of hepatic impairment may be considered. When aminotransferase elevations stabilize or resolve, omaveloxolone may be reinitiated with an appropriate increased frequency of monitoring of liver function per label. We propose patients who pause treatment may have testing repeated after 2 weeks, while those with resolving aminotransferase elevations may reinitiate omaveloxolone with stepwise dose titrations and testing every 2 weeks for ≈ 3 months. Use considerations herein may inform decisions on monitoring and managing ALT and AST elevations, which potentially help to encourage the treatment adherence needed to achieve the slowing of FA progression seen in MOXIe.Graphical abstract available for this article.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistence to Ocrelizumab Compared with Other Disease-Modifying Therapies for Multiple Sclerosis: Results from the German NeuroTransData Registry.","authors":"Stefan Braune, Petra Dirks, Seya Colloud, Qing Wang, Evan Davies, Yanic Heer, Mel Zürcher, Diana Sun, Arnfin Bergmann","doi":"10.1007/s40120-025-00762-6","DOIUrl":"https://doi.org/10.1007/s40120-025-00762-6","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment persistence is critical to obtaining full therapeutic benefit and can indicate favorable outcomes. This study examined real-world persistence with ocrelizumab (OCR) versus other disease-modifying therapies (DMTs) and its association with outcomes in relapsing-remitting multiple sclerosis (RRMS) using German NeuroTransData (NTD) registry data.</p><p><strong>Methods: </strong>This retrospective cohort analysis included outpatients with RRMS who initiated a DMT between January 2014 and April 2022. DMT initiation date was defined as the index date. DMTs were grouped into OCR, injectable, oral, oral for highly active disease (oral HA), and other intravenous (IV) therapies. Persistence, based on having continuous records of a DMT for 2 years from index date, was evaluated within each group. Association between persistence and the risk of relapse, 3-months confirmed disability progression (3mCDP), and sick leave were assessed.</p><p><strong>Results: </strong>Overall, 3907 patients with RRMS were included. OCR users had the highest persistence at 2 years (93%), then oral HA (78%), oral (67%), natalizumab (67%), and injectable therapies (55%). Compared with OCR users, patients initiating injectable (hazard ratio [HR] 8.51, 95% confidence interval [CI] 4.03-17.90), oral (HR 5.92, 95% CI 2.81-12.50), oral HA (HR 3.49, 95% CI 1.63-7.48) therapies, and natalizumab (HR 5.47, 95% CI 2.47-12.10) were more likely to discontinue. Adverse events (32.47%), lack of efficacy (21.17%), and patient-driven factors (19.73%) were the main reasons for discontinuation. Compared with persisters, non-persisters were associated with higher risks of relapse activity (rate ratio: 2.18, 95% CI 1.98-2.39), 3mCDP (rate ratio 1.52, 95% CI 1.28-1.77), and sick leave (rate ratio 1.71, 95% CI 1.49-1.98).</p><p><strong>Conclusion: </strong>In a German real-world setting, patients initiating OCR achieved higher rates of persistence over 2 years compared with those on other DMTs. High persistence was associated with lower risk of clinical disease activity, disease progression, and sick leave.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Atogepant in Healthy Lactating Female Participants: Results from a Phase 1 Lactation Study.","authors":"Ramesh R Boinpally, Jonathan H Smith, Rosa L De Abreu Ferreira, Joel M Trugman","doi":"10.1007/s40120-025-00772-4","DOIUrl":"https://doi.org/10.1007/s40120-025-00772-4","url":null,"abstract":"<p><strong>Introduction: </strong>Atogepant is approved for the preventive treatment of migraine and is taken orally once daily. This work aimed to characterize the plasma and milk pharmacokinetics of atogepant in lactating females.</p><p><strong>Methods: </strong>An open-label, phase 1 study (NCT05892757) was conducted in 12 healthy, lactating adult women 1-6 months postpartum from July 11, 2023, to February 22, 2024. A single 60-mg dose of atogepant was administered to participants to determine atogepant's plasma and milk pharmacokinetics, the excretion of atogepant in breast milk, and the relative infant dose (RID). Atogepant was analyzed using validated LC-MS/MS assays in plasma and breast milk samples collected up to 24 h after dosing and during specified intervals through 24 h, respectively. Plasma and milk pharmacokinetic parameters were estimated using non-compartmental methods and compared using linear mixed-effects models. Safety was assessed via adverse event reporting, clinical labs, vital signs, and ECGs throughout the study.</p><p><strong>Results: </strong>The mean (range) milk-to-plasma ratio for atogepant was 0.076 (0.023-0.104). With nearly undetectable levels of atogepant in breast milk 16-24 h after dosing, the cumulative mean (range) amount of atogepant excreted in breast milk over 24 h was 0.009 mg (0.005-0.016 mg; 0.015% of 60-mg dose), and the mean (range) RID was 0.19% (0.06-0.33%). The mean plasma and milk peak concentrations of atogepant were 779 ng/mL and 57.0 ng/mL, respectively, and the corresponding AUC values were 3270 ng·h/mL and 238 ng·h/mL, respectively. Atogepant exposures in breast milk were 93% lower compared to plasma. Two participants (16.7%) experienced AEs. These included abdominal pain (n = 1) and dyspepsia (n = 1), both of which were non-serious and mild in severity. No new safety signals were identified in this small group of healthy lactating women.</p><p><strong>Conclusion: </strong>The cumulative mean amount of atogepant recovered in breast milk over 24 h following a 60-mg dose was 0.009 mg, with a RID of 0.19%. CLINICAL TRIAL REGISTRATION: NCT05892757; https://clinicaltrials.gov/study/NCT05892757 .</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}