Interim Analysis of Istradefylline Effects on Tremor in Parkinson's Disease Patients—Promising Benefits on Tremor Control
Irma Zhang1, Michelle Umali2, Gonul Ozay2, Luke Lovelace2, Michael Barry3, Lina Ariza Serrano2, Alexandre Mason-Sharma2, Lana Raslan2, Yasar Torres-Yaghi2, Fernando Pagan2
1Neurology, Georgetown University School of Medicine, 2Neurology, Georgetown University Hospital, 3Pritzker Institute of Biomedical Science and Engineering, Illinois Institute of Technology
Objective:

To evaluate the effect of istradefylline on motor symptoms in tremor-dominant Parkinson’s disease.

Background:
Istradefylline is an adenosine A2A antagonist used to address “OFF” episodes in PD. Patients report improvement in tremor when treated with istradefylline, but no studies have been conducted thus far on this subject.
Design/Methods:

In this 6-month open-label, single-arm, pilot study, 27 patients with PD were treated with 40 mg daily istradefylline (after titrating up from 20 mg for two weeks) as add-on therapy for motor symptom management. Selected patients have levodopa-resistant tremor-dominant PD. Patient motor and non-motor symptoms were evaluated through MDS-UPDRS part I-IV at baseline and 24 weeks. Additional MDS-UPDRS Part III assessments were completed at weeks four and eight.

Ten patients have completed the study so far. Total MDS-UPDRS part III and tremor scale scores (Parts 3.15-3.18) were analyzed for each visit. Differences were calculated between baseline, 8 weeks, and 24 weeks.
Results:

The sums of the tremor scale scores within MDS-UPDRS part III were compared at 8 and 24 weeks vs. baseline for the 10 patients who have completed the study. There was an observed mean reduction of 7.4 points between 8w and baseline and 7.6 points between 24w and baseline (p < 10-6 for both time points, two-tailed permutation test).

MDS-UPDRS Part III total decreased by an average of 25.6 points between 8w and baseline (decreased in 9/10 patients, p = 0.002148), and 23.7 between 24w and baseline (decreased in 10/10 patients, p = 0.001953). Analysis of MDS-UPDRS Part III total data used two-tailed sign tests.
Conclusions:

Istradefylline was effective in decreasing both the tremor subcomponent and total MDS-UPDRS Part III score for patients who have completed the study. Additional findings are incoming as the remaining patients complete the study, including tremor amplitude scores utilizing a state-of-the art tremor mobile app.

10.1212/WNL.0000000000205879