Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD

Background: Ten-year follow-up results from the Parkinson's Disease Research Group of the United Kingdom trial demonstrated that there were no long-term advantages to initiating treatment with bromocriptine compared with l-dopa in early Parkinson disease (PD). Increased mortality in patients on selegiline combined with l-dopa led to premature termination of this arm after 6 years. Methods: Between 1985 and 1990, 782 patients were recruited into an open pragmatic multicenter trial and were randomized to l-dopa/decarboxylase inhibitor (DDCI), l-dopa/DDCI plus selegiline, or bromocriptine. The main endpoints were mortality, disability, and motor complications. For final follow-up, health-related quality of life and mental function were also assessed. Results: Median duration of follow-up at final assessment was 14 years in the 166 (21%) surviving participants who could be contacted. After adjustment for baseline characteristics, disability scores were better in the l-dopa than in the bromocriptine arm (Webster: 16.6 vs 19.8; p = 0.03; Northwestern University Disability: 34.3 vs 30.0, p = 0.05). Physical functioning (difference 20.8; 95% CI 10.0, 31.6; p < 0.001) and physical summary scores (difference 5.2; 95% CI 0.7, 9.7; p = 0.03) on the 36-item short-form health survey were also superior on l-dopa. Differences in mortality rates and prevalence of dyskinesias, motor fluctuations, and dementia were not significantly different. Conclusion: Initial treatment with the dopamine agonist bromocriptine did not reduce mortality or motor disability and the initially reduced frequency in motor complications was not sustained. We found no evidence of a long-term benefit or clinically relevant disease-modifying effect with initial dopamine agonist treatment.