Objective: To estimate the longitudinal effect of different dopamine therapies on the Movement Disorder Society-Sponsored Unified Parkinson’s Disease Rating Scale Part II (MDS-UPDRS II) among individuals with Parkinson’s disease diagnosed within the past 3 years (early PD).

Background: PD is the second most prevalent neurodegenerative disease. While dopamine replacing therapies do not modify the underlying disease pathology, they can improve motor symptoms of PD and affect the interpretation of clinical progression scales.

Method: In Fox Insight, the largest PD cohort study to date, we emulated two PD treatment scenarios among early PD participants. Scenario 1 compared regimens of stable dopamine-monotherapies (levodopa, dopamine agonist, or MAO-B inhibitors) at enrollment (visit 1) and continuing for 2 or more visits (for approximately 1 year follow up, on average). Scenario2 compared treatment-naïve participants who, if they started dopamine-monotherapies, did so after enrollment after visit 1, 2, or 3. To estimate causal effects of these regimens, we used marginal structural models to account for confounding both time-varying (by previous treatments and MDS-UPDRSII score) and baseline (age, age at PD diagnosis, and BMI). Furthermore, we used inverse probability weights of censoring to account for censoring.

Results: Of the 13,187 early PD participants at enrollment, 2526 (19%) participants were treatment-naïve, 5939 (45%) on levodopa, 831 (6%) on dopamine agonists, and 696 (5%) on MAO-B inhibitors monotherapy. In Scenario 1, the longitudinal MDS-UPDRS II trajectories were similar among the three monotherapy regimens, for visits 2 through 5. In Scenario 2, the trajectories for visits 2 through 5 differed depending on when monotherapy started. For example, at visit 5, participants who started monotherapy before visit 2 had an adjusted MDS-UPDRS-II score that was 3.30 units lower (95%CI: -6.08, -0.52) compared to those who stayed treatment-naïve for the first 3 visits.

Conclusion: In early PD, an important factor in MDS-UPDRS II trajectories was timing of initiating monotherapy in treatment-naïve participants, with less progression reported among those who started earlier. More research is needed to examine if these patterns persist after 2 years. Nevertheless, overall PD progression continued despite the dopaminergic medication, warranting the need for disease modifying therapy for PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-dopamine-replacement-therapies-on-mds-updrs-ii/