Risk factors for developing dyskinesia among Parkinson's disease patients with wearing-off: J-FIRST

Background: Dyskinesia frequently occurs during long-term treatment with levodopa in patients with Parkinson's disease (PD) and impacts quality of life. Few studies have examined risk factors for developing dyskinesia in PD patients exhibiting wearing-off. Therefore, we investigated the risk factors and impact of dyskinesia in PD patients exhibiting wearing-off. Methods: We investigated the risk factors and impact of dyskinesia in a 1-year observational study of Japanese PD patients exhibiting wearing-off (J-FIRST). Risk factors were assessed by logistic regression analyses in patients without dyskinesia at study entry. Mixed-effect models were used to evaluate the impact of dyskinesia on changes in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Part I and PD Questionnaire (PDQ)-8 scores from one timepoint before dyskinesia was observed. Results: Of 996 patients analyzed, 450 had dyskinesia at baseline, 133 developed dyskinesia within 1 year, and 413 did not develop dyskinesia. Female sex (odds ratio [95% confidence interval]: 2.636 [1.645–4.223]) and administration of a dopamine agonist (1.840 [1.083–3.126]), a catechol-O-methyltransferase inhibitor (2.044 [1.285–3.250]), or zonisamide (1.869 [1.184–2.950]) were independent risk factors for dyskinesia onset. MDS-UPDRS Part I and PDQ-8 scores increased significantly after the onset of dyskinesia (least-squares mean change [standard error] at 52 weeks: 1.11 [0.52], P = 0.0336; 1.53 [0.48], P = 0.0014; respectively). Conclusion: Female sex and administration of a dopamine agonist, a catechol-O-methyltransferase inhibitor, or zonisamide were risk factors for dyskinesia onset within 1 year in PD patients exhibiting wearing-off. Nonmotor symptoms and quality of life deteriorated after dyskinesia onset.