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Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: The STRIDE‐PD study
Author(s) -
Stocchi Fabrizio,
Rascol Olivier,
Kieburtz Karl,
Poewe Werner,
Jankovic Joseph,
Tolosa Eduardo,
Barone Paulo,
Lang Anthony E.,
Olanow C. Warren
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22060
Subject(s) - entacapone , dyskinesia , medicine , carbidopa , catechol o methyl transferase , parkinson's disease , levodopa , hazard ratio , anesthesia , randomized controlled trial , clinical endpoint , disease , confidence interval , allele , biochemistry , chemistry , gene
Objective L‐dopa is the most widely used and most effective therapy for Parkinson disease (PD), but chronic treatment is associated with motor complications in the majority of patients. It has been hypothesized that providing more continuous delivery of L‐dopa to the brain would reduce the risk of motor complications, and that this might be accomplished by combining L‐dopa with entacapone, an inhibitor of catechol‐O‐methyltransferase, to extend its elimination half‐life. Methods We performed a prospective 134‐week double‐blind trial comparing the risk of developing dyskinesia in 747 PD patients randomized to initiate L‐dopa therapy with L‐dopa/carbidopa (LC) or L‐dopa/carbidopa/entacapone (LCE), administered 4× daily at 3.5‐hour intervals. The primary endpoint was time to onset of dyskinesia. Results In comparison to LC, patients receiving LCE had a shorter time to onset of dyskinesia (hazard ratio, 1.29; p = 0.04) and increased frequency at week 134 (42% vs 32%; p = 0.02). These effects were more pronounced in patients receiving dopamine agonists at baseline. Time to wearing off and motor scores were not significantly different, but trended in favor of LCE treatment. Patients in the LCE group received greater L‐dopa dose equivalents than LC‐treated patients ( p < 0.001). Interpretation Initiating L‐dopa therapy with LCE failed to delay the time of onset or reduce the frequency of dyskinesia compared to LC. In fact, LCE was associated with a shorter time to onset and increased frequency of dyskinesia compared to LC. These results may reflect that the treatment protocol employed did not provide continuous L‐dopa availability and the higher L‐dopa dose equivalents in the LCE group. ANN NEUROL 2010;68:18–27