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

Richard Gray*, Natalie Ives, Caroline Rick, Smitaa Patel, Alastair Gray, Crispin Jenkinson, Emma McIntosh, Keith Wheatley, Adrian Williams, Carl E. Clarke, P. Sandercock, C. Baigent, P. Crome, A. Williams, R. Abbott, M. Baker, B. Castleton, C. E. Clarke, C. Counsell, A. K. Deb & 31 others S. Fairweather, R. Fitzpatrick, A. Gray, N. Ives, C. Jenkinson, G. MacPhee, T. Malone, D. Mant, E. McIntosh, A. Ming, P. Morrish, P. Ohri, V. Pearce, B. Wood, P. Worth, P. Au, T. Boodell, V. Cheed, C. E. Clarke, J. Daniels, F. Dowling, A. Edmondson, L. Caie, R. Caslake, C. Counsell, P. Crowley, J. Gordon, C. Harris, M. A. Macleod, K. Taylor, PD MED Collaborative Grp

*Corresponding author for this work

Research output: Contribution to journalArticle

128 Citations (Scopus)

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; 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 (p

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.

Original languageEnglish
Pages (from-to)1196-1205
Number of pages10
JournalThe Lancet
Volume384
Issue number9949
Early online date11 Jun 2014
DOIs
Publication statusPublished - 27 Sep 2014

Keywords

  • quality-of-life
  • questionnaire PDQ-39
  • progression
  • therapy
  • trials

Cite this

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. / Gray, Richard; Ives, Natalie; Rick, Caroline; Patel, Smitaa; Gray, Alastair; Jenkinson, Crispin; McIntosh, Emma; Wheatley, Keith; Williams, Adrian; Clarke, Carl E.; Sandercock, P.; Baigent, C.; Crome, P.; Williams, A.; Abbott, R.; Baker, M.; Castleton, B.; Clarke, C. E.; Counsell, C.; Deb, A. K.; Fairweather, S.; Fitzpatrick, R.; Gray, A.; Ives, N.; Jenkinson, C.; MacPhee, G.; Malone, T.; Mant, D.; McIntosh, E.; Ming, A.; Morrish, P.; Ohri, P.; Pearce, V.; Wood, B.; Worth, P.; Au, P.; Boodell, T.; Cheed, V.; Clarke, C. E.; Daniels, J.; Dowling, F.; Edmondson, A.; Caie, L.; Caslake, R.; Counsell, C.; Crowley, P.; Gordon, J.; Harris, C.; Macleod, M. A.; Taylor, K.; PD MED Collaborative Grp.

In: The Lancet, Vol. 384, No. 9949, 27.09.2014, p. 1196-1205.

Research output: Contribution to journalArticle

Gray, R, Ives, N, Rick, C, Patel, S, Gray, A, Jenkinson, C, McIntosh, E, Wheatley, K, Williams, A, Clarke, CE, Sandercock, P, Baigent, C, Crome, P, Williams, A, Abbott, R, Baker, M, Castleton, B, Clarke, CE, Counsell, C, Deb, AK, Fairweather, S, Fitzpatrick, R, Gray, A, Ives, N, Jenkinson, C, MacPhee, G, Malone, T, Mant, D, McIntosh, E, Ming, A, Morrish, P, Ohri, P, Pearce, V, Wood, B, Worth, P, Au, P, Boodell, T, Cheed, V, Clarke, CE, Daniels, J, Dowling, F, Edmondson, A, Caie, L, Caslake, R, Counsell, C, Crowley, P, Gordon, J, Harris, C, Macleod, MA, Taylor, K & PD MED Collaborative Grp 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', The Lancet, vol. 384, no. 9949, pp. 1196-1205. https://doi.org/10.1016/S0140-6736(14)60683-8
Gray, Richard ; Ives, Natalie ; Rick, Caroline ; Patel, Smitaa ; Gray, Alastair ; Jenkinson, Crispin ; McIntosh, Emma ; Wheatley, Keith ; Williams, Adrian ; Clarke, Carl E. ; Sandercock, P. ; Baigent, C. ; Crome, P. ; Williams, A. ; Abbott, R. ; Baker, M. ; Castleton, B. ; Clarke, C. E. ; Counsell, C. ; Deb, A. K. ; Fairweather, S. ; Fitzpatrick, R. ; Gray, A. ; Ives, N. ; Jenkinson, C. ; MacPhee, G. ; Malone, T. ; Mant, D. ; McIntosh, E. ; Ming, A. ; Morrish, P. ; Ohri, P. ; Pearce, V. ; Wood, B. ; Worth, P. ; Au, P. ; Boodell, T. ; Cheed, V. ; Clarke, C. E. ; Daniels, J. ; Dowling, F. ; Edmondson, A. ; Caie, L. ; Caslake, R. ; Counsell, C. ; Crowley, P. ; Gordon, J. ; Harris, C. ; Macleod, M. A. ; Taylor, K. ; PD MED Collaborative Grp. / 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. In: The Lancet. 2014 ; Vol. 384, No. 9949. pp. 1196-1205.
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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; 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.",
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author = "Richard Gray and Natalie Ives and Caroline Rick and Smitaa Patel and Alastair Gray and Crispin Jenkinson and Emma McIntosh and Keith Wheatley and Adrian Williams and Clarke, {Carl E.} and P. Sandercock and C. Baigent and P. Crome and A. Williams and R. Abbott and M. Baker and B. Castleton and Clarke, {C. E.} and C. Counsell and Deb, {A. K.} and S. Fairweather and R. Fitzpatrick and A. Gray and N. Ives and C. Jenkinson and G. MacPhee and T. Malone and D. Mant and E. McIntosh and A. Ming and P. Morrish and P. Ohri and V. Pearce and B. Wood and P. Worth and P. Au and T. Boodell and V. Cheed and Clarke, {C. E.} and J. Daniels and F. Dowling and A. Edmondson and L. Caie and R. Caslake and C. Counsell and P. Crowley and J. Gordon and C. Harris and Macleod, {M. A.} and K. Taylor and {PD MED Collaborative Grp}",
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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 Grp

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

VL - 384

SP - 1196

EP - 1205

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9949

ER -