Analysis of pramipexole dose–response relationships in Parkinson's disease

Ying Wang,1 Sheng-Gang Sun,2 Sui-Qiang Zhu,3 Chun-Feng Liu,4 Yi-Ming Liu,5 Qing Di,6 Hui-Fang Shang,7 Yan Ren,8 Wei Xiang,9 Sheng-Di Chen1 1Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of Neurology, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 3Department of Neurology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 4Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, 5Department of Neurology, Qilu Hospital Affiliated to Shandong University, Jinan, 6Department of Neurology, Nanjing Brain Hospital, Nanjing, 7Department of Neurology, West China Hospital Affiliated to Sichuan University, Chengdu, 8Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, 9Medical Department, Boehringer Ingelheim (China) Investment Co., Ltd., Shanghai, People’s Republic ofChina Background: Pramipexole (PPX), a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson’s disease (PD). A critical dose level above which a better benefit-to-harm ratio exists has not been examined.Methods: Chinese PD patients (n=464) were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II) and Motor Examination (III) of the Unified Parkinson’s Disease Rating Scale (UPDRS II+III) was used as a covariate for final score adjustment.Results: Sustained-release (SR) and immediate-release (IR) PPX showed similar efficacy based on score changes at 18 weeks, with comparable tolerability. Approximately two-third of patients received PPX at ≥1.5 mg/d, and one fourth of patients had ≥20% tremor contribution to UPDRS II+III. After treatment, patients receiving PPX ≥1.5 mg/d showed better improvement in UPDRS II+III scores (P=0.0025), with similar trends with the IR and SR formulations. Patients with ≥20% tremor contribution showed better improvement in UPDRS II+III scores (P=0.0017). No differences were seen based on PD stage or combined levodopa dose. The overall proportions of adverse events (AEs) were similar. More patients discontinued because of intolerable side effects, and more investigator-defined drug-related AEs were recorded in the