Objective: To compare the long-term impact of levodopa monotherapy versus early adjunctive therapy combined with levodopa on mortality in PD.

Background: Although dopaminergic therapy improves motor symptoms in Parkinson’s disease (PD), it remains unclear whether early treatment with levodopa alone or with adjunctive medications influences long-term survival.

Method: We conducted a nationwide, population-based retrospective cohort study using the Korean National Health Insurance Service (NHIS)-Senior Cohort (2004-2019). Newly diagnosed PD patients were categorized into initial treatment groups: levodopa monotherapy versus levodopa with early adjunctive medications, including monoamine Oxidase B (MAO-B) inhibitor, dopamine agonist (DA), and catechol-O-methyltransferase (COMT) inhibitor. A machine learning-based causal survival forest model estimated adjusted differences in 5-year restricted mean survival time (RMST) for all-cause mortality after adjustment for demographic, socioeconomic, lifestyle, and clinical covariates, including levodopa equivalent daily dose and comorbidity burden.

Results: Among 4,949 patients, 2,816 (56.9%) received levodopa only, 288 (5.8%) received levodopa with MAO-B inhibitor, 1,645 (33.2%) with DA, and 200 (4.0%) with COMT inhibitor. Compared with levodopa alone, early adjunctive therapy with a MAO-B inhibitor was associated with a longer estimated survival (ΔRMST = 3.45 months; 95% CI, 1.92–4.98; P < 0.001), and therapy with a DA showed a smaller but similarly directed association (ΔRMST, 0.95 months; 95% CI, 0.09–1.82; P = 0.031). In contrast, adjunctive therapy with COMT inhibitors was not associated with a difference in 5-year RMST (ΔRMST, -1.64 months; 95% CI, -4.25–0.97; P = 0.217). The predicted treatment benefit of MAO-B inhibitors varied considerably among individuals, with the largest estimated survival benefits observed in older patients, whose highest quartile showed an RMST increase of 10.72 months (95% CI, 7.89–13.54).

Conclusion: In this observational analysis, early addition of adjunctive therapy to levodopa was associated with differences in survival outcomes. The age-related heterogeneity in treatment benefit observed in our study suggests the potential value of an individualized approach to dopaminergic therapy in early PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-dopaminergic-treatment-patterns-and-5-year-survival-in-parkinsons-disease-a-nationwide-observational-study/