Objective: To investigate the efficacy and safety of istradefylline for the treatment of postural abnormality in patients with Parkinson’s disease (PD).

Background: Postural abnormality in PD patients is often refractory to dopaminergic drugs, and currently, no established treatment approach exists. Istradefylline, an adenosine A_2A receptor antagonist, is indicated as an adjunctive treatment to levodopa preparations in PD patients experiencing OFF time and is currently available in Japan and the US.

Method: In a multicenter, open-label, 24-week prospective study, PD patients with postural abnormality receiving levodopa treatment and experiencing wearing-off phenomenon were administered oral istradefylline for 6 months: 20 mg/day for 4 weeks followed by 40 mg/day. The primary endpoint was the mean change from baseline to week 24 in the 14-item Unified Dystonia Rating Scale (UDRS) total score. Mean changes in Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) part I and III, Freezing of Gait Questionnaire, Clinical Global Impression-Global Improvement, PD Questionnaire-8 scores, and Modified Hoehn and Yahr scale (ON/OFF state) were secondary endpoints.

Results: Overall, 31 patients (female, 58.1%; mean [standard deviation] age, 73.3 [7.7] years) were enrolled. The mean (95% confidence interval [CI]) UDRS total score improved from baseline (15.2 [12.4, 18.0], n=25) over the study [Figure 1], with a significant mean (95% CI) improvement of 4.84 (1.97, 7.71; P=0.002 [by paired t-test]) at week 24. None of the severity scores for all 14 items of the UDRS worsened. The mean change (95% CI; regression coefficient) from baseline to week 24 in the MDS-UPDRS part III score was 7.84 (4.34, 11.34; −6.129; P<0.001 [by mixed effect model]). Other secondary endpoints did not change significantly. The most commonly reported adverse drug reactions (ADRs) were malaise, dyskinesia exacerbation, and visual hallucinations in 2 (6.5%) patients each. No serious ADRs were observed.

Conclusion: Topline results from this study demonstrated the efficacy and safety of istradefylline, a drug that acts by non-dopaminergic mechanism, in PD patients with postural abnormality. Istradefylline may be a potential treatment option for postural abnormality in PD patients treated with levodopa preparations and experiencing OFF time.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-istradefylline-in-parkinsons-disease-patients-with-postural-abnormality-results-from-a-multicenter-open-label-study-in-japan/