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: 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 contr...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Lancet
2014
|
| _version_ | 1797067213698498560 |
|---|---|
| author | Gray, R Ives, N Rick, C Patel, S Gray, A Jenkinson, C McIntosh, E Wheatley, K Williams, A Clarke, C |
| author_facet | Gray, R Ives, N Rick, C Patel, S Gray, A Jenkinson, C McIntosh, E Wheatley, K Williams, A Clarke, C |
| author_sort | Gray, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:53:09Z |
| format | Journal article |
| id | oxford-uuid:4c018e81-d862-4692-b18a-aafe0347edb4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:53:09Z |
| publishDate | 2014 |
| publisher | Lancet |
| record_format | dspace |
| spelling | oxford-uuid:4c018e81-d862-4692-b18a-aafe0347edb42022-03-26T15:46:58ZLong-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.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4c018e81-d862-4692-b18a-aafe0347edb4EnglishSymplectic Elements at OxfordLancet2014Gray, RIves, NRick, CPatel, SGray, AJenkinson, CMcIntosh, EWheatley, KWilliams, AClarke, CBACKGROUND: 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. |
| spellingShingle | Gray, R Ives, N Rick, C Patel, S Gray, A Jenkinson, C McIntosh, E Wheatley, K Williams, A Clarke, C 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. |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| work_keys_str_mv | AT grayr longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT ivesn longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT rickc longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT patels longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT graya longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT jenkinsonc longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT mcintoshe longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT wheatleyk longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT williamsa longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial AT clarkec longtermeffectivenessofdopamineagonistsandmonoamineoxidasebinhibitorscomparedwithlevodopaasinitialtreatmentforparkinsonsdiseasepdmedalargeopenlabelpragmaticrandomisedtrial |