Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: The STRIDE-PD study
Article first published online: 23 APR 2010
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 68, Issue 1, pages 18–27, July 2010
How to Cite
Stocchi, F., Rascol, O., Kieburtz, K., Poewe, W., Jankovic, J., Tolosa, E., Barone, P., Lang, A. E. and Olanow, C. W. (2010), Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: The STRIDE-PD study. Ann Neurol., 68: 18–27. doi: 10.1002/ana.22060
- Issue published online: 25 JUN 2010
- Article first published online: 23 APR 2010
- Accepted manuscript online: 23 APR 2010 12:00AM EST
- Manuscript Accepted: 5 APR 2010
- Manuscript Revised: 17 MAR 2010
- Manuscript Received: 22 DEC 2009
- Novartis Pharma A.G.
- Orion Copration
- Orion Pharma
Vol. 68, Issue 3, 412–413, Article first published online: 31 AUG 2010
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.
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.
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).
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