Cost-effectiveness of dopamine agonists and monoamine oxidase B inhibitors in Parkinson’s disease

Background: The PD MED study reported small but persistent benefits in patient‐rated mobility scores and quality of life from initiating therapy with levodopa compared with levodopa‐sparing therapies in early Parkinson's disease (PD). Objectives: The objective was to estimate the cost‐effectiveness of levodopa‐sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors compared with levodopa alone. Methods: PD MED is a pragmatic, open‐label randomized, controlled trial in which patients newly diagnosed with PD were randomly assigned between levodopa‐sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors ) and levodopa alone. Mean quality‐adjusted life‐years and costs were calculated for each participant. Differences in mean quality‐adjusted life‐years and costs between levodopa and levodopa‐sparing therapies and between dopamine agonists and monoamine oxidase type B inhibitors were estimated using linear regression. Results: Over a mean observation period of 4 years, levodopa was associated with significantly higher quality‐adjusted life‐years (difference, 0.18; 95% CI, 0.05–0.30; P < 0.01) and lower mean costs (£3390; £2671–£4109; P < 0.01) than levodopa‐sparing therapies, the difference in costs driven by the higher costs of levodopa‐sparing therapies. There were no significant differences in the costs of inpatient, social care, and institutional care between arms. There was no significant difference in quality‐adjusted life‐years between those allocated dopamine agonists and monoamine oxidase type B inhibitors (0.02; −0.17 to 0.13 in favor of dopamine agonists; P = 0.81); however costs were significantly lower for those allocated monoamine oxidase type B inhibitors (£2321; £1628–£3015; P < 0.01) because of the higher costs of dopamine agonists. There were no significant differences between arms for other costs. Conclusions: Initial treatment with levodopa is highly cost‐effective compared with levodopa‐sparing therapies. Monoamine oxidase type B inhibitors, as initial levodopa‐sparing therapy was more cost‐effective, with similar quality‐adjusted life‐years but lower costs than dopamine agonists

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson's disease progressio

Background: Parkinson?s disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson?s DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression.Methods/design: Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. Study population: approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson?s Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson?s Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson?s disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-?, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow-up, and genetic studies (DNA and RNA) at baseline will be performed in a subgroup of subjects (300 PD patients and 100 control subjects). Study periods: (1) recruitment period, from November, 2015 to February, 2017 (basal assessment); (2) follow-up period, 5 years; (3) closing date of clinical follow-up, May, 2022. Funding: Public/Private. Discussion: COPPADIS-2015 is a challenging initiative. This project will provide important information on the natural history of PD and the value of various biomarkers

Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy : The PD MED Randomized Clinical Trial

Funding/Support: The PD MED clinical trial was supported by funding from the Health Technology Assessment Programme of the UK National Institute for Health Research (project number 98/03/02), the UK Department of Health through March 2012 (University of Birmingham Clinical Trials Unit, supporting the salaries of Mss Ives and Patel), the UK Medical Research Council (Mr R. Gray), and Parkinson’s UK (Dr McIntosh). We thank all of the patients who agreed to enter the study, the many investigators who also contributed to the clinical trial, and NHS Digital, which provided data on mortality and data from the Hospital Episodes Statistics database. The investigators received no payment or other compensation for taking part in the PD MED clinical trial.Peer reviewedPublisher PD

Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson's disease (PD MED): a large, open-label, pragmatic randomised trial

Background<p></p> Whether initial treatment for Parkinson's disease should consist of levodopa, dopamine agonists, or monoamine oxidase type B inhibitors (MAOBI) is uncertain. We aimed to establish which of these three classes of drug, as initial treatment, provides the most effective long-term control of symptoms and best quality of life for people with early Parkinson's disease.<p></p> Methods<p></p> In this pragmatic, open-label randomised trial, patients newly diagnosed with Parkinson's disease were randomly assigned (by telephone call to a central office; 1:1:1) between levodopa-sparing therapy (dopamine agonists or MAOBI) and levodopa alone. Patients and investigators were not masked to group assignment. Primary outcomes were the mobility dimension on the 39-item patient-rated Parkinson's disease questionnaire (PDQ-39) quality-of-life scale (range 0–100 with six points defined as the minimally important difference) and cost-effectiveness. Analysis was intention to treat. This trial is registered, number ISRCTN69812316.<p></p> Findings<p></p> Between Nov 9, 2000, and Dec 22, 2009, 1620 patients were assigned to study groups (528 to levodopa, 632 to dopamine agonist, 460 to MAOBI). With 3-year median follow-up, PDQ-39 mobility scores averaged 1·8 points (95% CI 0·5–3·0, p=0·005) better in patients randomly assigned to levodopa than those assigned to levodopa-sparing therapy, with no increase or attrition of benefit during 7 years' observation. PDQ-39 mobility scores were 1·4 points (95% CI 0·0–2·9, p=0·05) better in patients allocated MAOBI than in those allocated dopamine agonists. EQ-5D utility scores averaged 0·03 (95% CI 0·01–0·05; p=0·0002) better with levodopa than with levodopa-sparing therapy; rates of dementia (hazard ratio [HR] 0·81, 95% CI 0·61–1·08, p=0·14), admissions to institutions (0·86, 0·63–1·18; p=0·4), and death (0·85, 0·69–1·06, p=0·17) were not significantly different, but the upper CIs precluded any substantial increase with levodopa compared with levodopa-sparing therapy. 179 (28%) of 632 patients allocated dopamine agonists and 104 (23%) of 460 patients allocated MAOBI discontinued allocated treatment because of side-effects compared with 11 (2%) of 528 patients allocated levodopa (p<0·0001).<p></p> Interpretation<p></p> Very small but persistent benefits are shown for patient-rated mobility scores when treatment is initiated with levodopa compared with levodopa-sparing therapy. MAOBI as initial levodopa-sparing therapy was at least as effective as dopamine agonists