Pub Date : 2025-12-08DOI: 10.1001/jamaneurol.2025.4825
Gert Jan Lammers,Giuseppe Plazzi,Emmanuel Mignot,Fabio Pizza,Yves Dauvilliers,Lucie Barateau,Paul Maruff,Thomas E Scammell,Robert D Latzman,Melissa Naylor,Tina Olsson,Ellie Stukalin,Shinichiro Tanaka,Dmitri Volfson,Vahe Khachadourian,Brian T Harel
ImportanceCognitive symptoms negatively impact people with narcolepsy type 1 (NT1). While the effects of orexin receptor 2 (OX2R) agonists have been explored on diagnostic features of the disorder (excessive daytime sleepiness and cataplexy), effects on cognitive symptoms are not characterized.ObjectiveTo explore the effects of oveporexton, an oral OX2R-selective agonist, on cognition in people with NT1.Design, Setting, and ParticipantsThis is a secondary analysis of the TAK-861-2001 phase 2, 8-week, parallel-group, double-blind, placebo-controlled randomized clinical trial, conducted from January 2023 to December 2023, with a 4-week follow-up period. TAK-861-2001 was a multicenter study conducted in clinical settings. Eligible participants were 18 to 70 years of age, with an International Classification of Sleep Disorders, Third Edition diagnosis of NT1. Data analysis was performed from July 2024 to July 2025.InterventionsParticipants were randomized 1:1:1:1:1 to twice-daily oral oveporexton or matching placebo, dosed 3 hours apart, in dose groups of 0.5/0.5 mg, 2/2 mg, 2/5 mg, 7 mg/placebo, or placebo/placebo, for 8 weeks.Main Outcomes and MeasuresCognitive symptoms were assessed using the Psychomotor Vigilance Task (PVT) for attention, the Continuous Paired Associate Learning (CPAL) test for memory, and the One Back (ONB) test and International Digit Symbol Substitution Test-symbols (IDSST-s) for executive function.ResultsOf 161 eligible individuals screened, 48 did not meet study inclusion criteria, 1 withdrew, and 112 were included in the study. Of 112 participants, mean (SD) age was 34.0 (11.5) years, and 58 participants (51.8%) were female. A total of 112 participants were randomized and received 1 or more doses of oveporexton (0.5/0.5 mg, n = 23; 2/2 mg, n = 21; 2/5 mg, n = 23; 7 mg, n = 23) or placebo (n = 22). Oveporexton improved attention, memory, and executive function over 8 weeks. Least-squares (LS) mean placebo-adjusted changes from baseline were -10.77 (95% CI, -16.74 to -4.79), -9.45 (95% CI, -15.66 to -3.24), -8.60 (95% CI, -14.84 to -2.36), and -8.69 (95% CI, -14.90 to -2.47) PVT lapses with 0.5/0.5 mg, 2/2 mg, 2/5 mg, and 7 mg/placebo doses, respectively. LS mean placebo-adjusted changes were -22.52 (95% CI, -34.95 to -10.10), -16.92 (95% CI, -30.12 to -3.71), -15.51 (95% CI, -28.82 to -2.21), and -17.59 (95% CI, -30.50 to -4.68) for CPAL errors; -0.05 (95% CI, -0.10 to -0.01), -0.07 (95% CI, -0.12 to -0.02), -0.07 (95% CI, -0.12 to -0.02), and -0.05 (95% CI, -0.10 to 0.00) units for ONB log10-transformed performance speed; and 4.72 (95% CI, -1.38 to 10.83), 7.33 (95% CI, 1.06-13.61), 7.85 (95% CI, 1.75-13.95), and 11.82 (95% CI, 5.75-17.89) for IDSST-s correct responses.Conclusions and RelevanceIn this secondary analysis of the TAK-861-2001 randomized clinial trial, the OX2R agonist oveporexton improved NT1-associated cognitive symptoms in adults.Trial RegistrationClinicalTrials.gov Identifier: NCT05687903.
{"title":"Effects of Oveporexton, an Orexin Receptor 2-Selective Agonist, on Cognition in Narcolepsy Type 1: A Secondary Analysis of a Randomized Clinical Trial.","authors":"Gert Jan Lammers,Giuseppe Plazzi,Emmanuel Mignot,Fabio Pizza,Yves Dauvilliers,Lucie Barateau,Paul Maruff,Thomas E Scammell,Robert D Latzman,Melissa Naylor,Tina Olsson,Ellie Stukalin,Shinichiro Tanaka,Dmitri Volfson,Vahe Khachadourian,Brian T Harel","doi":"10.1001/jamaneurol.2025.4825","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4825","url":null,"abstract":"ImportanceCognitive symptoms negatively impact people with narcolepsy type 1 (NT1). While the effects of orexin receptor 2 (OX2R) agonists have been explored on diagnostic features of the disorder (excessive daytime sleepiness and cataplexy), effects on cognitive symptoms are not characterized.ObjectiveTo explore the effects of oveporexton, an oral OX2R-selective agonist, on cognition in people with NT1.Design, Setting, and ParticipantsThis is a secondary analysis of the TAK-861-2001 phase 2, 8-week, parallel-group, double-blind, placebo-controlled randomized clinical trial, conducted from January 2023 to December 2023, with a 4-week follow-up period. TAK-861-2001 was a multicenter study conducted in clinical settings. Eligible participants were 18 to 70 years of age, with an International Classification of Sleep Disorders, Third Edition diagnosis of NT1. Data analysis was performed from July 2024 to July 2025.InterventionsParticipants were randomized 1:1:1:1:1 to twice-daily oral oveporexton or matching placebo, dosed 3 hours apart, in dose groups of 0.5/0.5 mg, 2/2 mg, 2/5 mg, 7 mg/placebo, or placebo/placebo, for 8 weeks.Main Outcomes and MeasuresCognitive symptoms were assessed using the Psychomotor Vigilance Task (PVT) for attention, the Continuous Paired Associate Learning (CPAL) test for memory, and the One Back (ONB) test and International Digit Symbol Substitution Test-symbols (IDSST-s) for executive function.ResultsOf 161 eligible individuals screened, 48 did not meet study inclusion criteria, 1 withdrew, and 112 were included in the study. Of 112 participants, mean (SD) age was 34.0 (11.5) years, and 58 participants (51.8%) were female. A total of 112 participants were randomized and received 1 or more doses of oveporexton (0.5/0.5 mg, n = 23; 2/2 mg, n = 21; 2/5 mg, n = 23; 7 mg, n = 23) or placebo (n = 22). Oveporexton improved attention, memory, and executive function over 8 weeks. Least-squares (LS) mean placebo-adjusted changes from baseline were -10.77 (95% CI, -16.74 to -4.79), -9.45 (95% CI, -15.66 to -3.24), -8.60 (95% CI, -14.84 to -2.36), and -8.69 (95% CI, -14.90 to -2.47) PVT lapses with 0.5/0.5 mg, 2/2 mg, 2/5 mg, and 7 mg/placebo doses, respectively. LS mean placebo-adjusted changes were -22.52 (95% CI, -34.95 to -10.10), -16.92 (95% CI, -30.12 to -3.71), -15.51 (95% CI, -28.82 to -2.21), and -17.59 (95% CI, -30.50 to -4.68) for CPAL errors; -0.05 (95% CI, -0.10 to -0.01), -0.07 (95% CI, -0.12 to -0.02), -0.07 (95% CI, -0.12 to -0.02), and -0.05 (95% CI, -0.10 to 0.00) units for ONB log10-transformed performance speed; and 4.72 (95% CI, -1.38 to 10.83), 7.33 (95% CI, 1.06-13.61), 7.85 (95% CI, 1.75-13.95), and 11.82 (95% CI, 5.75-17.89) for IDSST-s correct responses.Conclusions and RelevanceIn this secondary analysis of the TAK-861-2001 randomized clinial trial, the OX2R agonist oveporexton improved NT1-associated cognitive symptoms in adults.Trial RegistrationClinicalTrials.gov Identifier: NCT05687903.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"53 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1001/jamaneurol.2025.4856
Mackenzie Henderson,Daniel B Horton,Vikram Bhise,Greta Bushnell,Chintan V Dave
{"title":"Out-of-Pocket and Total Health Care Costs Among Commercially Insured Adults and Children With Multiple Sclerosis.","authors":"Mackenzie Henderson,Daniel B Horton,Vikram Bhise,Greta Bushnell,Chintan V Dave","doi":"10.1001/jamaneurol.2025.4856","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4856","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"38 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ImportancePrior authorization (PA) is widely used by insurers to control health care costs and promote high-value care, but it can create significant barriers to accessing medications. This is particularly concerning in neurology, where timely treatment is critical to avoid disease progression and optimize patient outcomes.ObjectiveTo assess the consequences, barriers, and facilitators of PA policies affecting access to pharmacologic treatment in 6 common neurologic conditions-Alzheimer disease, Parkinson disease, multiple sclerosis, migraine, cerebrovascular disease, and epilepsy-with focus on impacts on patients, clinicians, and administrators.Evidence ReviewThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines for scoping reviews were followed, and the study protocol was registered on Open Science Framework. MEDLINE and Embase were searched up to November 1, 2024, using Ovid for studies that assessed the role of PA as a primary or secondary outcome for the 6 included neurologic conditions, or for neurology broadly if strongly applicable to the study aim, after the signage of the Affordable Care Act in March 2010. Abstract screening and full-text review were done in duplicate. Key information was charted in extraction, including study characteristics, demographics, methods, results, and implications for relevant stakeholders. The results were aggregated and thematically analyzed.FindingsA total of 364 studies were identified using our search strategy on Ovid, 278 records were screened, and 20 studies were included in this review. The most frequently identified consequences for patients were delays in care (60%) and increase in disease activity (25%). The most frequently identified consequence for clinicians (35%) and administrators (15%) was time burden. The most common facilitators were the use of clinical pharmacists or technicians (20%) and health system specialty pharmacies (15%).Conclusions and RelevanceAccording to the results of this scoping review, PA can contribute to significant access barriers for people with neurological conditions and is associated with burden for all stakeholders involved. Reforms to PA can work towards more equitable access to medications for patients.
重要性事先授权（PA）被保险公司广泛用于控制医疗保健成本和促进高价值护理，但它可能对获取药物造成重大障碍。这在神经病学中尤其值得关注，及时治疗对于避免疾病进展和优化患者预后至关重要。目的评估PA政策影响6种常见神经系统疾病（阿尔茨海默病、帕金森病、多发性硬化症、偏头痛、脑血管疾病和癫痫）药物治疗可及性的后果、障碍和促进因素，重点关注对患者、临床医生和管理人员的影响。证据评价遵循系统评价和荟萃分析首选报告项目（PRISMA）范围评价报告指南，研究方案在开放科学框架上注册。MEDLINE和Embase检索截止到2024年11月1日，使用Ovid进行研究，评估PA作为6种纳入的神经系统疾病的主要或次要结局的作用，或在2010年3月《平价医疗法案》（Affordable Care Act）发布后，如果强烈适用于研究目标，则广泛用于神经学。摘要筛选和全文审查一式两份。提取的关键信息被绘制成图表，包括研究特征、人口统计学、方法、结果以及对相关利益相关者的影响。对结果进行汇总和主题分析。使用我们在Ovid上的搜索策略，共发现了364项研究，筛选了278项记录，其中20项研究被纳入本综述。对患者最常见的后果是护理延误（60%）和疾病活动性增加（25%）。对于临床医生（35%）和管理人员（15%）来说，最常见的后果是时间负担。最常见的辅助人员是临床药师或技术人员（20%）和卫生系统专业药房（15%）。结论和相关性根据本范围审查的结果，PA可能对神经系统疾病患者的获取造成重大障碍，并与所有相关利益相关者的负担相关。PA改革可以使患者更公平地获得药物。
{"title":"Barriers and Consequences of Prior Authorization for Neurologic Medications: A Scoping Review.","authors":"Evelyn Gotlieb,Bamby Joseph,Leah Blank,Nathalie Jetté","doi":"10.1001/jamaneurol.2025.4560","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4560","url":null,"abstract":"ImportancePrior authorization (PA) is widely used by insurers to control health care costs and promote high-value care, but it can create significant barriers to accessing medications. This is particularly concerning in neurology, where timely treatment is critical to avoid disease progression and optimize patient outcomes.ObjectiveTo assess the consequences, barriers, and facilitators of PA policies affecting access to pharmacologic treatment in 6 common neurologic conditions-Alzheimer disease, Parkinson disease, multiple sclerosis, migraine, cerebrovascular disease, and epilepsy-with focus on impacts on patients, clinicians, and administrators.Evidence ReviewThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines for scoping reviews were followed, and the study protocol was registered on Open Science Framework. MEDLINE and Embase were searched up to November 1, 2024, using Ovid for studies that assessed the role of PA as a primary or secondary outcome for the 6 included neurologic conditions, or for neurology broadly if strongly applicable to the study aim, after the signage of the Affordable Care Act in March 2010. Abstract screening and full-text review were done in duplicate. Key information was charted in extraction, including study characteristics, demographics, methods, results, and implications for relevant stakeholders. The results were aggregated and thematically analyzed.FindingsA total of 364 studies were identified using our search strategy on Ovid, 278 records were screened, and 20 studies were included in this review. The most frequently identified consequences for patients were delays in care (60%) and increase in disease activity (25%). The most frequently identified consequence for clinicians (35%) and administrators (15%) was time burden. The most common facilitators were the use of clinical pharmacists or technicians (20%) and health system specialty pharmacies (15%).Conclusions and RelevanceAccording to the results of this scoping review, PA can contribute to significant access barriers for people with neurological conditions and is associated with burden for all stakeholders involved. Reforms to PA can work towards more equitable access to medications for patients.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"33 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1001/jamaneurol.2025.4213
Weiyao Yin, Jonas F Ludvigsson, Sven Sandin
{"title":"Autism and Parkinsonism-Terminology and Confounding-Reply.","authors":"Weiyao Yin, Jonas F Ludvigsson, Sven Sandin","doi":"10.1001/jamaneurol.2025.4213","DOIUrl":"10.1001/jamaneurol.2025.4213","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"1288-1289"},"PeriodicalIF":21.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145377474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1001/jamaneurol.2025.4726
Joshua D Grill
{"title":"Blood Tests for Alzheimer Disease-What to Do With the Holy Grail.","authors":"Joshua D Grill","doi":"10.1001/jamaneurol.2025.4726","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4726","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"175 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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