Abstract
ABSTRACTBackgroundBoth patients and physicians may choose to delay initiation of dopamine replacement therapy in Parkinson's disease (PD) for various reasons. We used observational data to estimate the effect of earlier treatment in PD. Observational data offer a valuable source of evidence, complementary to controlled trials.MethodWe studied the Parkinson's Progression Markers Initiative cohort of patients with de novo PD to estimate the effects of duration of PD treatment during the first 2 years of follow‐up, exploiting natural interindividual variation in the time to start first treatment. We estimated the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part III (primary outcome) and several functionally relevant outcomes at 2, 3, and 4 years after baseline. To adjust for time‐varying confounding, we used marginal structural models with inverse probability of treatment weighting and the parametric g‐formula.ResultsWe included 302 patients from the Parkinson's Progression Markers Initiative cohort. There was a small improvement in MDS‐UPDRS Part III scores after 2 years of follow‐up for patients who started treatment earlier, and similar, but nonstatistically significant, differences in subsequent years. We found no statistically significant differences in most secondary outcomes, including the presence of motor fluctuations, nonmotor symptoms, MDS‐UPDRS Part II scores, and the Schwab and England Activities of Daily Living Scale.ConclusionEarlier treatment initiation does not lead to worse MDS‐UPDRS motor scores and may offer small improvements. These findings, based on observational data, are in line with earlier findings from clinical trials. Observational data, when combined with appropriate causal methods, are a valuable source of additional evidence to support real‐world clinical decisions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Highlights
For the MDSUPDRS III, fewer measurements were available because not all assessments fulfilled the off criteria and were considered missing; 155 MDS-UPDRS III measurements were available at year 2, 178 at year 3, and 194 at year 4
Prior well-controlled randomized controlled trials (RCTs) found no evidence for a disease-modifying effect, but these studies may not necessarily have reflected real-life prescription behavior, which could result in other outcomes
We describe the long-term effects of variations in medication prescription behavior as tested in a large observational data set provided by the Parkinson’s Progression Markers Initiative (PPMI) cohort
Summary
Our goal was to estimate the effects of variations in duration of PD treatment on disease-related outcomes. We aimed to answer the question “if all patients would receive 0.5 year treatment within the first 2 years of follow-up, what would the average change in outcomes be if we changed this to 1.5 years?” We present the estimated linear effect of a change in treatment duration of 1 year. It is important to note that we aimed to estimate the effect of earlier treatment initiation, but from this analysis—which focused entirely on clinical outcomes, and not on biomarkers for underlying pathological disease progression—it is not possible to determine what mechanisms are at play
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