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
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.
作者信息
Lanore Aymeric, Januel Edouard, Bertille Nathalie, Fabbri Margherita, Mariani Louise-Laure, Mangone Graziella, Sambin Sara, Menon Poornima Jayadev, Tir Melissa, Bereau Matthieu, Meissner Wassilios G, Thiriez Claire, Marques Ana, Remy Philippe, Dupont Gwendoline, Moro Elena, Defebvre Luc, Houeto Jean Luc, Thobois Stéphane, Azulay Jean-Philippe, Geny Christian, Frismand Solène, Damier Philippe, Giordana Caroline, Castelnovo Giovanni, Ansquer Solène, De Maindreville Anne Doe, Drapier Sophie, Maltête David, Tranchant Christine, Rascol Olivier, Tubach Florence, De Rycke Yann, Corvol Jean-Christophe
机构信息
Department of Neurology, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, NS-Park/FCRIN Network, Paris, France.
Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, CIC-1901, 75013, Paris, France.
出版信息
CNS Drugs. 2025 May 25. doi: 10.1007/s40263-025-01193-5.
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.
GOV IDENTIFIER
NCT04888364. Registered June 2021.
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，可单独使用或联合使用。目前缺乏它们在现实生活中用于PD患者早期管理的数据。我们的目标是使用全国性的PD队列评估早期治疗策略对运动和神经精神并发症发生发展的影响。
方法
NS-PARK是一组于2011年至2021年期间从法国26个PD专家中心招募的PD患者。我们分析了入组时病程少于5年且无运动并发症的患者。我们使用区间删失生存模型来评估治疗策略（左旋多巴单药治疗、左旋多巴替代疗法或左旋多巴联合疗法）与运动波动、异动症、冲动控制及相关行为（ICRBs）、淡漠、精神病/幻觉和日间嗜睡之间的关联。分析对性别、年龄、病程、多巴胺能剂量和疾病严重程度进行了校正。
结果
我们纳入了1722例患者（女性占38.4%，中位年龄67.7岁）。入组时，41%的患者接受左旋多巴单药治疗，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异动症风险相关（风险比（HR）0.48，95%置信区间（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了ICRBs风险（HR 4.06，95% CI [2.48 - 6.67]；HR 5.16，95% CI [3.00 - 8.86]）并降低了淡漠风险（HR 0.36，95% CI [0.26 - 0.49]；HR 0.52，95% CI [0.39 - 0.69]）。未发现与精神病/幻觉或日间嗜睡有关联。
结论
在这个现实生活队列中，我们的数据支持左旋多巴替代疗法与较低的异动症和淡漠风险相关，但与左旋多巴单药治疗相比，ICRBs风险更高。
政府标识符
NCT04888364。于2021年6月注册。
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