Session Information
Date: Tuesday, September 24, 2019
Session Title: Parkinsonisms and Parkinson-Plus
Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: Using observational longitudinal data to estimate the long-term effect of the duration of levodopa treatment in the first two years after diagnosis.
Background: Levodopa is an effective symptomatic treatment for patients with Parkinson’s disease. However, both patients and physicians may choose to delay initiation of levodopa therapy for various reasons. One concern is that levodopa might negatively affect disease progression. The recent LEAP study, a double blind, placebo controlled trial with 445 early Parkinson patients, found no disease-modifying effect for levodopa[1]. However, selected study populations, as used in randomized controlled trials, usually do not account for the typical heterogeneity within a real-life population. Observational data, without strict in- and exclusion criteria, are more representative of the true patient population.
Method: We used the PPMI cohort with 423 recently diagnosed PD patients [2] to estimate the treatment effect of one additional year of levodopa during the first two years after diagnosis. Predefined endpoints included the MDS-UPDRS part I, II and III, Montreal Cognitive Assessment and Schwab and England Activities of Daily Living scale. We compared a naïve estimate, simple adjustment for baseline confounders, Marginal Structural Models using Inverse Probability Weighting and Marginal Structural Models using the g-formula, to adjust for (time-varying) confounding.
Results: Models that take the time-varying nature of the treatment initiation after diagnosis into account, effectively removed some of the confounding that seems to be present in simpler models. For most outcome measures we found no significant different treatment effect for early versus delayed start of levodopa therapy. Preliminary results show slightly lower MDS-UPDRS part III scores in longer levodopa treatment, which may be caused by unadjusted confounding or residual symptomatic medication effects.
Conclusion: The lack of differential effects of early or delayed start of levodopa therapy based on observational data is in line with earlier findings from clinical trials. The benefits of observational data, such as the sample potentially being more representative of the true population of PD, and the relative ease with which such data can be gathered, provide a valuable source of additional evidence to support real-world clinical decisions.
References: 1. Verschuur, C.V.M., et al., Randomized Delayed-Start Trial of Levodopa in Parkinson’s Disease. N Engl J Med, 2019. 380(4): p. 315-324. 2. Parkinson Progression Marker Initiative, The Parkinson Progression Marker Initiative (PPMI). Prog Neurobiol, 2011. 95(4): p. 629-35.
To cite this abstract in AMA style:
L. Vd Heuvel, J. Krijthe, L. Evers, M. Meinders, B. Post, T. Heskes, B. Bloem. Estimating the long-term effect of early levodopa treatment initiation in Parkinson’s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/estimating-the-long-term-effect-of-early-levodopa-treatment-initiation-in-parkinsons-disease/. Accessed September 7, 2024.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/estimating-the-long-term-effect-of-early-levodopa-treatment-initiation-in-parkinsons-disease/