Aymeric Lanore, Edouard Januel, Nathalie Bertille, Margherita Fabbri, Louise-Laure Mariani, Graziella Mangone, Sara Sambin, Poornima Jayadev Menon, Melissa Tir, Matthieu Bereau, Wassilios G Meissner, Claire Thiriez, Ana Marques, Philippe Remy, Gwendoline Dupont, Elena Moro, Luc Defebvre, Jean Luc Houeto, Stéphane Thobois, Jean-Philippe Azulay, Christian Geny, Solène Frismand, Philippe Damier, Caroline Giordana, Giovanni Castelnovo, Solène Ansquer, Anne Doe De Maindreville, Sophie Drapier, David Maltête, Christine Tranchant, Olivier Rascol, Florence Tubach, Yann De Rycke, Jean-Christophe Corvol
{"title":"帕金森病不同早期治疗后的运动和非运动并发症：来自法国NS-PARK队列的真实临床和治疗数据的纵向分析","authors":"Aymeric Lanore, Edouard Januel, Nathalie Bertille, Margherita Fabbri, Louise-Laure Mariani, Graziella Mangone, Sara Sambin, Poornima Jayadev Menon, Melissa Tir, Matthieu Bereau, Wassilios G Meissner, Claire Thiriez, Ana Marques, Philippe Remy, Gwendoline Dupont, Elena Moro, Luc Defebvre, Jean Luc Houeto, Stéphane Thobois, Jean-Philippe Azulay, Christian Geny, Solène Frismand, Philippe Damier, Caroline Giordana, Giovanni Castelnovo, Solène Ansquer, Anne Doe De Maindreville, Sophie Drapier, David Maltête, Christine Tranchant, Olivier Rascol, Florence Tubach, Yann De Rycke, Jean-Christophe Corvol","doi":"10.1007/s40263-025-01193-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.</p><p><strong>Methods: </strong>NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity.</p><p><strong>Results: </strong>We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness.</p><p><strong>Conclusions: </strong>In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT04888364. Registered June 2021.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"879-891"},"PeriodicalIF":7.4000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Motor and Non-motor Complications Following Different Early Therapies in Parkinson's Disease: Longitudinal Analysis of Real-Life Clinical and Therapeutic Data from the French NS-PARK Cohort.\",\"authors\":\"Aymeric Lanore, Edouard Januel, Nathalie Bertille, Margherita Fabbri, Louise-Laure Mariani, Graziella Mangone, Sara Sambin, Poornima Jayadev Menon, Melissa Tir, Matthieu Bereau, Wassilios G Meissner, Claire Thiriez, Ana Marques, Philippe Remy, Gwendoline Dupont, Elena Moro, Luc Defebvre, Jean Luc Houeto, Stéphane Thobois, Jean-Philippe Azulay, Christian Geny, Solène Frismand, Philippe Damier, Caroline Giordana, Giovanni Castelnovo, Solène Ansquer, Anne Doe De Maindreville, Sophie Drapier, David Maltête, Christine Tranchant, Olivier Rascol, Florence Tubach, Yann De Rycke, Jean-Christophe Corvol\",\"doi\":\"10.1007/s40263-025-01193-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.</p><p><strong>Methods: </strong>NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity.</p><p><strong>Results: </strong>We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness.</p><p><strong>Conclusions: </strong>In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT04888364. Registered June 2021.</p>\",\"PeriodicalId\":10508,\"journal\":{\"name\":\"CNS drugs\",\"volume\":\" \",\"pages\":\"879-891\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40263-025-01193-5\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40263-025-01193-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/25 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：左旋多巴、多巴胺激动剂（DA）和单胺氧化酶抑制剂（MAOI）均被批准为帕金森病（PD）的一线治疗药物，无论是单药还是联合用药。在现实生活中，它们在PD患者早期管理中的使用数据缺乏。我们的目的是通过一个全国性的PD队列来评估早期治疗策略对运动和神经精神并发症发展的影响。方法：NS-PARK是2011年至2021年间从法国26个PD专家中心招募的PD患者队列。我们分析了病程少于5年且纳入时无运动并发症的患者。我们使用间隔筛选生存模型来评估治疗策略（左旋多巴单一疗法、左旋多巴替代疗法或左旋多巴联合疗法）与运动波动、运动障碍、冲动控制及相关行为（ICRBs）、冷漠、精神病/幻觉和白天嗜睡之间的关系。分析根据性别、年龄、疾病持续时间、多巴胺能剂量和疾病严重程度进行调整。结果：纳入1722例患者（38.4%为女性，中位年龄67.7岁）。纳入时，41%接受左旋多巴单一疗法，31%接受左旋多巴替代疗法，28%接受左旋多巴联合疗法。与左旋多巴单药治疗相比，左旋多巴替代疗法与较低的运动障碍风险相关（危险比（HR） 0.48, 95%可信区间（CI）[0.28-0.84]），但在运动波动方面无显著差异。左旋多巴替代疗法和联合疗法均增加ICRBs风险(HR 4.06, 95% CI [2.48-6.67]；HR 5.16, 95% CI[3.00-8.86])和冷漠风险降低(HR 0.36, 95% CI [0.26-0.49]；Hr 0.52, 95% ci[0.39-0.69])。没有发现与精神病/幻觉或白天嗜睡有关。结论：在这个现实生活中的队列中，我们的数据支持左旋多巴替代疗法与运动障碍和冷漠的低风险之间的关联，但与左旋多巴单药治疗相比，ICRBs的风险更高。临床试验：政府标识符：NCT04888364。2021年6月注册。
Motor and Non-motor Complications Following Different Early Therapies in Parkinson's Disease: Longitudinal Analysis of Real-Life Clinical and Therapeutic Data from the French NS-PARK Cohort.
Background: Levodopa, dopamine agonists (DA) and monoamine oxidase inhibitors (MAOI) are all approved first-line therapies for Parkinson's disease (PD), as monotherapy or in combination. Data on their use in the early management of patients with PD in real-life are lacking. Our objective was to assess the impact of early therapeutic strategies on the development of motor and neuropsychiatric complications using a nationwide PD cohort.
Methods: NS-PARK is a cohort of patients with PD recruited between 2011 and 2021 from 26 expert centres for PD in France. We analysed the patients with less than 5-years disease duration and no motor complications at inclusion. We used interval censoring survival models to assess the associations between therapeutic strategies (levodopa monotherapy, levodopa alternative therapies or levodopa combinations) and motor fluctuations, dyskinesia, impulse control and related behaviours (ICRBs), apathy, psychosis/hallucination and daytime sleepiness. Analyses were adjusted for sex, age, disease duration, dopaminergic dose and disease severity.
Results: We included 1722 patients (38.4% female, median age 67.7 years). At inclusion, 41% received levodopa monotherapy, 31% received levodopa alternative therapies and 28% received levodopa combinations. Compared with levodopa monotherapy, levodopa alternative therapies were associated with a lower dyskinesia risk (hazard ratio (HR) 0.48, 95% confidence interval (CI)[0.28-0.84]), but there was no significant difference in motor fluctuations. Both levodopa alternative and combinations therapies increased ICRBs risk (HR 4.06, 95% CI [2.48-6.67]; HR 5.16, 95% CI [3.00-8.86]) and decreased apathy risk (HR 0.36, 95% CI [0.26-0.49]; HR 0.52, 95% CI [0.39-0.69]). No association was found with psychosis/hallucination or daytime sleepiness.
Conclusions: In this real-life cohort, our data supported an association between levodopa alternative therapies and a lower risk of dyskinesia and apathy, but a higher risk of ICRBs compared with levodopa monotherapy.
Clinicaltrials:
Gov identifier: NCT04888364. Registered June 2021.
期刊介绍：
CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes:
- Overviews of contentious or emerging issues.
- Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses.
- Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement.
- Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry.
- Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies.
Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
