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

Abstract

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.

Parkinson’s Disease Multimodal Complex Treatment (PD-MCT): Analysis of Therapeutic Effects and Predictors for Improvement

“…Since the scale depicts the impact of dyskinesia on activities of daily living and includes subjective as well as objective dyskinesia rating, it might be superior to the MDS-UPDRS IV in detecting treatment effects [ 57 ]. The UDysRS is frequently used in publications presenting positive effects of pharmacological agents as Amantadine on dyskinesia [ 58 , 59 , 60 ].…”

Nigral Iron Deposition Is Associated With Levodopa-Induced Dyskinesia in Parkinson’s Disease

“…Parkinson's disease (PD) is a progressive movement disorder caused primarily by the loss of nigrostriatal neurons and depletion of dopamine (Thomas and Beal, 2007). Dopamine replacement therapeutics, such as levodopa, relieve the symptoms of PD but can lead to a motor complication known as levodopa-induced dyskinesia (LID), which is a major cause of disability in PD patients (Pahwa et al, 2019). LID is observed in approximately 90% of PD patients after 10 years of levodopa treatment (Manson et al, 2012).…”

Impact of disease stage and age at Parkinson’s onset on patients’ primary concerns: Insights for targeted management

“…When an impact of dyskinesia on activities of daily living (ADLs) was evaluated, the percentage of patients reporting severe impact on ADLs by dyskinesia was less than 5%. Moderate impact was less than 30% whereas the majority reported mild or even no impact from dyskinesia [36]. Nevertheless, dyskinesia is the visible sign that might lead to social embarrassment or stigmatisation and continue to be a matter of debate on its impact on different subgroups of PD patients.…”