Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Nijmegen, The Netherlands.
Data Science Research Department, Institute for Computing and Information Sciences, Radboud University, Nijmegen, The Netherlands.
Mov Disord Clin Pract. 2024 Oct;11(10):1249-1256. doi: 10.1002/mdc3.14174. Epub 2024 Aug 2.
The ideal timing for initiating levodopa in newly diagnosed people with Parkinson's disease (PD) is uncertain due to limited data on the long-term effects of levodopa.
The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device-aided therapies, and the incidence of PD-related complications, such as fall-induced injuries.
Using nationwide claims data from Dutch hospitals (2012-2020), we grouped newly diagnosed PD individuals as "early initiators" (initiating levodopa within 2 years of diagnosis) or "nonearly initiators." We used the national death registry to assess mortality and health-care claims to assess PD-related complications and device-aided therapies. We used marginal structural models to compare mortality and device-aided therapy rates between groups, and a Poisson regression model to compare PD-related complication rates.
Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92-1.19) for early versus nonearly initiators. The risk ratio of receiving any device-aided therapy was 3.19 (95% CI 2.56-5.80). No association was observed with incidence of PD-related complications (incidence rate ratio: 1.00, 95% CI 0.96-1.05).
Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD-related complications, nor does it precipitate earlier occurrence of PD-related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.
由于缺乏关于左旋多巴长期影响的数据，新诊断为帕金森病（PD）的患者开始使用左旋多巴的理想时机尚不确定。
旨在研究早期左旋多巴的使用是否会推迟死亡率（主要结局）、需要辅助治疗设备以及 PD 相关并发症（如跌倒引起的损伤）的发生率。
利用荷兰医院的全国性索赔数据（2012-2020 年），我们将新诊断的 PD 患者分为“早期启动者”（在诊断后 2 年内开始使用左旋多巴）或“非早期启动者”。我们使用国家死亡登记处来评估死亡率，使用医疗保健索赔来评估 PD 相关并发症和辅助治疗设备的使用。我们使用边缘结构模型比较两组之间的死亡率和辅助治疗设备使用率，使用泊松回归模型比较 PD 相关并发症发生率。
在 29943 名新诊断的 PD 患者中（诊断时的平均年龄为 71.6 岁，女性占 38.5%），有 24847 名早期和 5096 名非早期左旋多巴的启动者。在中位数为 4.25 年的随访期间，有 8109 人（27.1%）死亡。早期与非早期启动者相比，死亡率的因果风险比为 1.04（95%置信区间 [CI]：0.92-1.19）。接受任何辅助治疗设备的风险比为 3.19（95% CI：2.56-5.80）。与 PD 相关并发症的发生率无关联（发病率比：1.00，95% CI：0.96-1.05）。
PD 患者的早期左旋多巴的使用既不会推迟也不会加速死亡率或 PD 相关并发症的发生，也不会导致 PD 相关并发症或死亡率更早发生。然而，我们不能排除由于死亡率的未测量风险因素导致的残余混杂因素对结果的影响。
