Long-term effect of initiating pramipexole vs levodopa in early Parkinson disease.
OBJECTIVE
To compare the long-term outcomes of subjects initially treated with pramipexole dihydrochloride with those of subjects initially treated with levodopa in the Comparison of the Agonist Pramipexole With Levodopa on Motor Complications of Parkinson's Disease (CALM-PD) trial.


METHODS
Up to 2 years of open extended follow-up of the CALM-PD subjects.


METHODS
Academic movement disorders clinics at 22 sites in the United States and Canada. Patients Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability were enrolled between October 1996 and August 1997, a subset of whom consented to extended follow-up until August 2003 (n = 222). Intervention Subjects were randomized to receive initial treatment with either pramipexole (n = 151) or levodopa (n = 150). Investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability.


METHODS
The primary outcome variable was the time-weighted average of self-reported disability scores in the "on" and "off" states as measured by the Schwab and England Activities of Daily Living Scale at the final visit. Secondary outcomes included the Unified Parkinson's Disease Rating Scale score, the presence and severity of dopaminergic motor complications, quality-of-life scale scores, Geriatric Depression Scale score, Epworth Sleepiness Scale score, and adverse events.


RESULTS
After a mean (SD) follow-up of 6.0 (0.2) years, mean (SD) self-reported weighted Schwab and England Activities of Daily Living Scale scores were similar in the initial pramipexole (79.9 [16.2]) and initial levodopa (82.5 [14.6]) groups (P = .19). Dopaminergic motor complications (wearing off, on-off effects, or dyskinesias) were more common in the initial levodopa group (68.4%) than in the initial pramipexole group (50.0%) (P = .002), although disabling dyskinesias were uncommon in both groups. The mean (SD) Epworth Sleepiness Scale score was significantly higher in the initial pramipexole group (11.3 [5.8]) than in the initial levodopa group (8.6 [4.7]) (P < .001). Mean (SD) changes from baseline in the total Unified Parkinson's Disease Rating Scale score did not significantly differ between the initial pramipexole (2.4 [17.4]) and initial levodopa (0.5 [17.1]) groups (P = .11).


CONCLUSIONS
The policies of initial pramipexole and initial levodopa use followed by open-label levodopa use resulted in similar self-reported disability 6 years after randomization. Persistent differences favoring initial pramipexole were seen in the rates of dopaminergic motor complications, with less severe somnolence favoring initial levodopa. Trial Registration clinicaltrials.gov Identifier: NCT00804479.
Department of Neurology, University of Rochester, 1351 Mt Hope Ave, Ste 220, Rochester, NY 14620, USA. kevin.biglan@ctcc.rochester.edu
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D000077487:Pramipexole; D011788:Quality of Life; D013995:Time; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D052160:Benzothiazoles; D007980:Levodopa; D000077487:Pramipexole