Tags

Type your tag names separated by a space and hit enter

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.
Lancet. 2014 Sep 27; 384(9949):1196-205.Lct

Abstract

BACKGROUND

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.

METHODS

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.

FINDINGS

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).

INTERPRETATION

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.

FUNDING

UK National Institute for Health Research Health Technology Assessment Programme and UK Department of Health.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Pragmatic Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24928805

Citation

PD Med Collaborative Group, et al. "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." Lancet (London, England), vol. 384, no. 9949, 2014, pp. 1196-205.
PD Med Collaborative Group, Gray R, Ives N, et al. 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. Lancet. 2014;384(9949):1196-205.
Gray, R., Ives, N., Rick, C., Patel, S., Gray, A., Jenkinson, C., McIntosh, E., Wheatley, K., Williams, A., & Clarke, C. E. (2014). 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. Lancet (London, England), 384(9949), 1196-205. https://doi.org/10.1016/S0140-6736(14)60683-8
PD Med Collaborative Group, et al. 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. Lancet. 2014 Sep 27;384(9949):1196-205. PubMed PMID: 24928805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - ,, AU - Gray,Richard, AU - Ives,Natalie, AU - Rick,Caroline, AU - Patel,Smitaa, AU - Gray,Alastair, AU - Jenkinson,Crispin, AU - McIntosh,Emma, AU - Wheatley,Keith, AU - Williams,Adrian, AU - Clarke,Carl E, Y1 - 2014/06/11/ PY - 2014/6/15/entrez PY - 2014/6/15/pubmed PY - 2014/12/15/medline SP - 1196 EP - 205 JF - Lancet (London, England) JO - Lancet VL - 384 IS - 9949 N2 - BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme and UK Department of Health. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/24928805/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(14)60683-8 DB - PRIME DP - Unbound Medicine ER -