Early versus delayed initiation of entacapone in levodopa-treated patients with Parkinson's disease: a long-term, retrospective analysis.
BACKGROUND
We analysed data from three clinical trials in Parkinson's disease (PD) patients with wearing-off to determine whether early enhancement of levodopa therapy with entacapone can lead to better long-term outcomes than delayed entacapone treatment.


METHODS
Post-hoc analysis of pooled data from three randomized, double-blind, placebo-controlled studies and their long-term, open-label extension phases. In all three studies, patients on levodopa/dopa-decarboxylase inhibitor (DDCI) were first randomized to entacapone ('early-start' group) or placebo ('delayed-start' group) for the initial 6-month double-blind phase, after which all patients received open-label levodopa/DDCI and entacapone treatment for up to 5 years.


RESULTS
A total of 488 PD patients with wearing-off were included in the analysis. A statistically significant benefit of early initiation of levodopa/DDCI and entacapone was found, with an improvement in Unified Parkinson's Disease Rating Scale Part III (motor) score of -1.66 (95% confidence intervals [-3.01, -0.31]) points compared with the delayed-start treatment group (P < 0.05). Levodopa/DDCI and entacapone therapy was well tolerated. There was no excess of dyskinesia in the early-start group.


CONCLUSIONS
These data suggest that early rather than delayed addition of entacapone to levodopa/DDCI in PD patients with wearing-off provides a modest clinical benefit over levodopa/DDCI that is maintained for up to 5 years.
Nissinen
H
H
Orion Pharma, Espoo, Finland. helena.nissinen@orionpharma.com
Kuoppamäki
M
M
Leinonen
M
M
Schapira
A H
AH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002396:Catechols / Q000008:administration & dosage* / Q000009:adverse effects; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies
D000978:Antiparkinson Agents; D002396:Catechols; D009570:Nitriles; D007980:Levodopa; C071192:entacapone