Browse by author
Lookup NU author(s): Dr Timothy Cassidy, Steven Dodds, Dr Akif Gani, Dr Rachael LawsonORCiD, Dr Jane Noble, Professor Richard Walker
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2014 Elsevier Ltd. 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.
Author(s): 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, Gray R, Hawker R, Herd C, Hilken N, Ives N, Kaur S, Ottridge R, Patel S, Peto L, Rick C, Sidile C, Tomlinson C, Tyler E, Wheatley K, Winkles N, Gray A, McIntosh E, Kent S, Fitzpatrick R, Jenkinson C, Caie L, Caslake R, Coleman R, Counsell C, Crowley P, Gerrie L, Gordon J, Harris C, Leslie V, Macleod MA, Taylor K, Barker R, Forsyth D, Halls M, Lennox G, Young J, Azie E, Barrett J, Monaghan A, Turnbull C, Vanek H, Blake D, Manford M, Thangarajah N, Johnson M, Wallis P, Carr P, Cochrane L, Prescott R, Rose A, Drover M, Karunaratne P, McLaren A, Jones E, Nasar M, Bayliss M, Jones AP, Lewis B, Dunn A, Eckley M, Price J, Woodman G, Forsyth D, Halls M, Young J, Aldridge G, Bhuvanendran N, Lewis S, Mann C, Patel K, Ghaus N, Grueger A, Mallinson B, Wihl G, Ballantyne S, Clarke CE, Coyle S, Hornabrook R, Hutchinson S, Irfan H, Lewthwaite A, Nicholl D, Poxon S, Ritch A, Davison J, Dodds S, Gray C, Nath U, Robinson G, Deb A, Aftab N, Read D, Villanueva L, Alderton L, Carr P, Cochrane L, Prescott R, Rose A, Burrows E, Fletcher P, Folkes E, Gilbert A, Hayes H, Morrow P, Silva M, Baxter G, Bell J, Gorman J, Lawrence J, Rhind G, Hindle J, Jones J, Ohri P, Parry M, Roberts E, Subashchandran R, Pycock C, Aspden L, Partington-Jones L, Raw J, Vanek H, Wadhwa U, Barber R, Haywood B, Heywood P, Lewis H, O'Sullivan K, Prout K, Whelan L, Whone A, Fletcher P, Folkes E, Fuller G, Medcalf P, Morrish P, Silva M, Aruldoss P, Farmery J, Liveley K, Shelbourn K, Sood V, Bouifraden K, Dalziel J, Evans C, Matheson P, Overstall P, Wales E, Ward G, Ponsford J, Graham IA, Grimmer SFM, Lockington TJ, Sheehan LJ, Williams H, Fuller J, Harrison P, Roche M, Shields S, Glasspool R, Hubbard I, Walters R, Barraclough C, McClung A, Moseley L, Pathirana CK, Abbott R, Critchley P, Wray LG, Kendall B, Lawden M, Lo N, Martey J, Rajabally Y, Simpson B, Abbott R, Critchley P, Kendall B, Lawden M, Martey J, Rajabally Y, Hindle J, Ohri P, Gale A, Phiri D, Sekaran L, Sharma A, Wijayasiri S, Fleary H, Monaghan A, Silverdale M, Vanek H, Walker D, McGee M, Senthil V, Reynolds S, Arnould D, Chong S, Diem D, Kundu B, Quinn N, Benamer H, Billings J, Corston R, D'Costa D, Green M, Shuri J, Cassidy T, Dodds S, Gani A, Lawson R, Noble J, Chan Y, Clipsham K, Cochius J, Dick D, Hipperson M, Lee M, Payne B, Reading F, Roche M, Sabanathan K, Shields S, Worth P, Harper G, Honan W, Oxborough L, Saunders J, Stanley J, McCann P, Edmonds P, Hand A, O'Hanlon S, Robinson L, Walker R, Bolam D, Liddle B, Ballantyne SL, Byravan R, Jones P, Guptha S, Noble C, Roychowdhury S, Ellis C, Harries -Jones R, Hillier C, Milligan N, Potter J, Ebenezer L, Raha S, Thompson S, Benamer H, Crouch R, Healy K, Hornabrook R, Johnson M, Nicholl D, Pall H, Praamstra P, Williams A, Beaumont D, Ell S, McGourty J, Jenkinson M, McHenry M, Scoble N, Vahid R, Findley L, Misbahuddin A, Adcock J, Chatterjee A, Collins H, Fairweather S, Flossman E, Greenhall R, Hart H, Shaw J, Singh S, Talbot K, Thompson S, Weir A, Gray D, Sood V, Sutherland S, Wilson M, Hughes T, Jones A, Morgan L, Sastry B, Abdel-Hafiz A, Al-Modaris F, Dutta S, Mallik T, Mondal B, Roberts J, Sinha S, Amar K, Atkins S, Devadason G, Martin A, Thompson C, Fenwick G, Gormley K, Gutowski N, Harris S, Harrower T, Hemsley A, Honan W, James M, Jeffreys O, Malone T, Pearce V, Sheridan R, Soper C, Sword J, Zeman A, Gordon C, McElwaine T, Pressly V, Chan D, Saha R, Howcroft D, Mugweni K, Robertson D, Stephens A, Whelan E, Wright A, Blane N, Burns S, Mutch W, Roberts R, Chikna E, Chamberlain J, Lee J, Marigold J, Adams J, Dulay J, Evans S, Frankel J, Garrard P, Gibb W, Gove R, Holmes C, Lawton N, Malik N, McElwaine T, Morgan S, Phipps H, Pressly V, Queen V, Roberts H, Tan R, Turner G, Weller R, Zaman S, O'Brien A, Grosset D, MacPhee G, McGonigal A, Vennard C, Rektorova I, Carey G, Castleton B, Dhakam Z, Kalcantera E, Long C, Mandal B, Martin V, Nari R, Nicholas V, Sunderland C, Franks S, Hammans S, Moffitt V, Rice-Oxley M, Elizabeth J, Logan A, Summers B, Cooper S, Darch W, Homan J, Hussain M, Sharratt D, Solanki T, Bennett J, Vassallo J, Ford A, Kendall G, Stocker K, Chaudhry A, Grubneac A, Kenton A, Lindahl A, Lismore J, McConville M, Peskett R, Ponsford J, Shehu A, Strens L, Hughes T, Sastry B, Barrett J, Turnbull C, Vanek H, Moore A, O'Brien I, Watling D, Wyatt L, Jones C, Mahan T, Ullyart K, Wood B, Desai H, Ferry P, Grubneac A, Ponsford J, Ray P, Rose P, Shehu A, Thanvi B, Waters S, Rizvi S, Sa'Adu A, Walker E, Berry G, Russell N, Lennox G, Ward T, Abrams J, Ashley S, Steiger M, Beal A, Hawkins J, Heller A, Jenkinson M, McHenry M, Samuel M, Scoble N, Vahid R, Caie L, Leslie V, Primrose W, Baker K, Buckley C, Bulley S, Gibbons D, Goodland R, Heywood P, Jones L, Martin L, Qadiri MR, Rashed K, Rowland -Axe R, Stone A, Whittuck M
Publication type: Article
Publication status: Published
Journal: The Lancet
Year: 2014
Volume: 384
Issue: 9949
Pages: 1196-1205
Print publication date: 27/09/2014
Online publication date: 11/06/2014
Acceptance date: 01/01/1900
ISSN (print): 0140-6736
ISSN (electronic): 1474-547X
Publisher: Lancet Publishing Group
URL: https://doi.org/10.1016/S0140-6736(14)60683-8
DOI: 10.1016/S0140-6736(14)60683-8
PubMed id: 24928805
Altmetrics provided by Altmetric
