Ten-year follow-up of three different initial treatments in de-novo PD - Arandomized trial

Background: The long-term effectiveness of three different initial drug reg imes in patients with early, mild PD was evaluated by the PD Research Group of the United Kingdom (PDRGUK). In 1995, the selegiline arm of the trial w as terminated following an interim analysis. Method: This was an open, rand omized trial. Between 1985 and 1990, 782 patients with de-novo PD were recr uited and randomized to one of three treatment arms: levodopa plus dopa dec arboxylase inhibitor; levodopa plus decarboxylase inhibitor and selegiline; or bromocriptine. The main endpoints were mortality, disability, and adver se events. Intention-to-treat analysis was used. Results: There was no sign ificant difference in mortality between the bromocriptine and the levodopa arms (hazard ratio 1.15 [95% CI 0.90, 1.47]). Patients initially randomized to bromocriptine had slightly worse disability scores throughout follow-up . This difference was significant during the first years. Patients in the b romocriptine arm returned to pretreatment disability levels one year earlie r than those in the levodopa arm. Patients randomized to bromocriptine had a significantly lower incidence of dyskinesias than those randomized to lev odopa (rate ratio 0.73 [95% CI 0.57, 0.93]). However, this difference was n ot significant when only moderate to severe dyskinesias were considered. Pa tients in the bromocriptine arm had slightly lower rates of dystonias and o n-off fluctuations, but moderate and severe forms were equally frequent in both arms. Conclusion: Starting treatment with the dopamine agonist bromocr iptine does not reduce mortality in PD. A slightly lower incidence of motor complications is achieved at the expense of significantly worse disability scores throughout the first years of therapy.