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)
T2 - a large, open-label, pragmatic randomised
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.
AU - Sandercock, P.
AU - Baigent, C.
AU - Crome, P.
AU - Williams, A.
AU - Abbott, R.
AU - Baker, M.
AU - Castleton, B.
AU - Clarke, C. E.
AU - Counsell, C.
AU - Deb, A. K.
AU - Fairweather, S.
AU - Fitzpatrick, R.
AU - Gray, A.
AU - Ives, N.
AU - Jenkinson, C.
AU - MacPhee, G.
AU - Malone, T.
AU - Mant, D.
AU - McIntosh, E.
AU - Ming, A.
AU - Morrish, P.
AU - Ohri, P.
AU - Pearce, V.
AU - Wood, B.
AU - Worth, P.
AU - Au, P.
AU - Boodell, T.
AU - Cheed, V.
AU - Clarke, C. E.
AU - Daniels, J.
AU - Dowling, F.
AU - Edmondson, A.
AU - Caie, L.
AU - Caslake, R.
AU - Counsell, C.
AU - Crowley, P.
AU - Gordon, J.
AU - Harris, C.
AU - Macleod, M. A.
AU - Taylor, K.
AU - PD MED Collaborative Group
PY - 2014/9/27
Y1 - 2014/9/27
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; 13=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 sideeffects compared with 11 (2%) of 528 patients allocated levodopa (pInterpretation 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.
AB - 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; 13=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 sideeffects compared with 11 (2%) of 528 patients allocated levodopa (pInterpretation 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.
KW - quality-of-life
KW - questionnaire PDQ-39
KW - progression
KW - therapy
KW - trials
U2 - 10.1016/S0140-6736(14)60683-8
DO - 10.1016/S0140-6736(14)60683-8
M3 - Article
SN - 0140-6736
VL - 384
SP - 1196
EP - 1205
JO - The Lancet
JF - The Lancet
IS - 9949
ER -
