Impact of dyskinesia on activities of daily living in Parkinson's disease: Results from pooled phase 3 ADS-5102 clinical trials

Abstract Introduction In Parkinson's disease, dyskinesias result from disease progression and chronic levodopa therapy. Using Unified Dyskinesia Rating Scale (UDysRS) data pooled from two pivotal trials of ADS-5102 (amantadine) extended-release capsules in dyskinetic patients, we assessed the impact of dyskinesia on activities of daily living (ADLs), and the effects of ADS-5102 versus placebo. Methods Patients had troublesome dyskinesia (≥1 h/day) and at least mild functional impact of dyskinesia per Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part IV, item 4.2. UDysRS Parts 1B, 3, and 4 scores at baseline were summarized descriptively. Twelve-week changes in score distributions and total scores were tested for significant differences between treatments. Results Among 196 patients, the majority (63%–73%) characterized their dyskinesia at baseline as having at least a mild impact on walking and balance ; public and social settings ; exciting or emotional settings ; doing hobbies and other activities ; handwriting ; and dressing (six of ten ADLs in UDysRS Part 1B). By clinician ratings (in Parts 3 and 4), greatest impairment was most often observed in the trunk (62% of patients) and occurred most often for the ADL of dressing (64% had at least moderate impairment). ADS-5102 significantly reduced the patient-rated impact of dyskinesia on six of ten ADLs in Part 1B, the clinician-rated intensity of dyskinesia in all seven body regions assessed in Part 3, and the clinician-rated disability during three of four ADL tasks assessed in Part 4. Improvements in Parts 1B, 3, and 4 total scores were also statistically significant. Conclusion Dyskinesia can impair multiple tasks of daily living. Further studies may help characterize its underreported impact. By several measures, ADS-5102 treatment was associated with significant improvement of dyskinesias.