Objective: To determine the effect of long-term treatment with istradefylline (IST) on the time to onset of dyskinesia in Parkinson’s disease (PD) patients with wearing-off (WO).

Background: As PD progresses and levodopa treatment is prolonged, motor complications such as WO and levodopa-induced dyskinesia become a major treatment challenge. IST is an adenosine A_2A receptor antagonist approved in Japan and the US as an adjunct to levodopa/decarboxylase inhibitors in PD patients with WO. The impact of IST on the onset of dyskinesia remains unclear.

Method: In this 3-year, multicenter, randomized, open-label, parallel-group controlled study, 214 levodopa-treated PD patients with WO, but not dyskinesia, were randomized (1:1) to treatment with IST (IST group, n=105) or without IST (non-IST group, n=109). The primary endpoint was the time to onset of dyskinesia. Secondary endpoints included the time to onset of troublesome dyskinesia, changes in PD symptom rating scales, and safety.

Results: Over 3 years, the incidence of dyskinesia was 37.9% and 41.1% in the IST and non-IST groups, respectively. The median time to onset of dyskinesia was 1100 days and 1082 days, respectively, which was not significantly different between the two groups. In a subgroup analysis, the time to onset of dyskinesia in patients older than the median age (68 years) was longer in the IST group than in the non-IST group. In patients aged less than 68 years and in those aged less than 60 years at PD onset, the time to onset of dyskinesia was longer in the non-IST group than in the IST group. There were no significant differences between the two groups in the time to onset of troublesome dyskinesia, the changes in Movement Disorder Society-Unified PD Rating Scale part I, II, III or IV total scores, or the incidence of adverse drug reactions during the study period.

Conclusion: Although the main side effect of IST has been reported to be dyskinesia, the effects of IST on the development of dyskinesia in PD patients with WO were not different to those of other anti-PD drugs. IST was as effective and tolerable as other drugs over a long period of time. Therefore, IST could be a feasible treatment option for PD patients with WO without exacerbating the onset of dyskinesia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-istradefylline-on-the-onset-of-dyskinesia-in-parkinsons-disease-patients-with-wearing-off-a-randomized-controlled-study-odyssei/