TY - JOUR
T1 - Levodopa Response in Patients with Early Parkinson Disease
T2 - Further Observations of the LEAP Study
AU - Frequin, Henrieke L.
AU - Schouten, Jason
AU - Verschuur, Constant V. M.
AU - Suwijn, Sven R.
AU - Boel, Judith A.
AU - Post, Bart
AU - Bloem, Bastiaan R.
AU - van Hilten, Johannes J.
AU - van Laar, Teus
AU - Tissingh, Gerrit
AU - Munts, Alexander G.
AU - Dijk, Joke M.
AU - Deuschl, G. nther
AU - Lang, Anthony
AU - Dijkgraaf, Marcel G. W.
AU - de Haan, Rob J.
AU - de Bie, Rob M. A.
N1 - Funding Information: H.L. Frequin, J. Schouten, C.V.M. Verschuur, S.R. Suwijn, J.A. Boel, B. Post, B.R. Bloem, J.J. van Hilten, T. van Laar, G. Tissingh, A.G. Munts, J.M. Dijk, G. Deuschl, A.E. Lang, M.G. Dijkgraaf, and R. J. de Haan report no disclosures relevant to the manuscript. R.M.A de Bie reports grants from the Parkinson Vereniging (Dutch patient organization), Stichting ParkinsonFonds (Dutch funding organization for Parkinson disease research), Stichting Parkinson Nederland (Dutch funding organization for Parkinson disease research), and the Netherlands Organization for Health Research and Development (Dutch governmental fund for health research, project number 0-82310-97-11031). These organizations did not have a role in the study design, data collection, and analysis, the interpretation of data, writing the report, or the decision to submit the paper for publication. Go to Neurology.org/N for full disclosures. Funding Information: This trial is supported by grants from the Netherlands Organization for Health Research and Development (Dutch governmental fund for health research, project number 0-82310-97-11031), Parkinson Vereniging (Dutch patient organization), Stichting ParkinsonFonds (Dutch funding organization for Parkinson disease research), and Stichting Parkinson Nederland (Dutch funding organization for Parkinson disease research). These organizations did not have a role in the study design, data collection, and analysis, the interpretation of data, writing the report, or the decision to submit the paper for publication. Publisher Copyright: © American Academy of Neurology.
PY - 2023/1/24
Y1 - 2023/1/24
N2 - Background and ObjectivesThe Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease.MethodsThe LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations.ResultsA total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early-and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was-0.33 for bradykinesia,-0.29 for rigidity, and-0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively,-0.49,-0.36, and-0.44 (small to medium effect); and from baseline to week 40, respectively,-0.32,-0.19, and-0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01).DiscussionIn patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier.Classification of EvidenceThis study provides Class II evidence that the effect of levodopa on bradykinesia, rigidity, and tremor is larger after 22 weeks compared with 4 weeks of treatment.Trial Registration InformationISRCTN30518857, EudraCT number 2011-000678-72.
AB - Background and ObjectivesThe Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease.MethodsThe LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations.ResultsA total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early-and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was-0.33 for bradykinesia,-0.29 for rigidity, and-0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively,-0.49,-0.36, and-0.44 (small to medium effect); and from baseline to week 40, respectively,-0.32,-0.19, and-0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01).DiscussionIn patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier.Classification of EvidenceThis study provides Class II evidence that the effect of levodopa on bradykinesia, rigidity, and tremor is larger after 22 weeks compared with 4 weeks of treatment.Trial Registration InformationISRCTN30518857, EudraCT number 2011-000678-72.
UR - http://www.scopus.com/inward/record.url?scp=85147045938&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000201448
DO - https://doi.org/10.1212/WNL.0000000000201448
M3 - Article
C2 - 36253105
SN - 0028-3878
VL - 100
SP - E367-E376
JO - Neurology
JF - Neurology
IS - 4
ER -