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Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study.
Ann Neurol. 2010 Jul; 68(1):18-27.AN

Abstract

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 4x 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.

Authors+Show Affiliations

Institute of Neurology, IRCCS San Raffaele Pisana, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20582993

Citation

Stocchi, Fabrizio, et al. "Initiating Levodopa/carbidopa Therapy With and Without Entacapone in Early Parkinson Disease: the STRIDE-PD Study." Annals of Neurology, vol. 68, no. 1, 2010, pp. 18-27.
Stocchi F, Rascol O, Kieburtz K, et al. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol. 2010;68(1):18-27.
Stocchi, F., Rascol, O., Kieburtz, K., Poewe, W., Jankovic, J., Tolosa, E., Barone, P., Lang, A. E., & Olanow, C. W. (2010). Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Annals of Neurology, 68(1), 18-27. https://doi.org/10.1002/ana.22060
Stocchi F, et al. Initiating Levodopa/carbidopa Therapy With and Without Entacapone in Early Parkinson Disease: the STRIDE-PD Study. Ann Neurol. 2010;68(1):18-27. PubMed PMID: 20582993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. AU - Stocchi,Fabrizio, AU - Rascol,Olivier, AU - Kieburtz,Karl, AU - Poewe,Werner, AU - Jankovic,Joseph, AU - Tolosa,Eduardo, AU - Barone,Paulo, AU - Lang,Anthony E, AU - Olanow,C Warren, PY - 2010/6/29/entrez PY - 2010/6/29/pubmed PY - 2010/7/21/medline SP - 18 EP - 27 JF - Annals of neurology JO - Ann Neurol VL - 68 IS - 1 N2 - 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 4x 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. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/20582993/Initiating_levodopa/carbidopa_therapy_with_and_without_entacapone_in_early_Parkinson_disease:_the_STRIDE_PD_study_ L2 - https://doi.org/10.1002/ana.22060 DB - PRIME DP - Unbound Medicine ER -