Baseline Dyskinesia Linked to Adverse Event Dyskinesia While on Istradefylline

Author(s):

Post-hoc data presented at the EAN Congress suggest patients with dyskinesia prior to starting treatment on the Kyowa Kirin agent were more likely to experience dyskinesia as an adverse event during treatment.

Stuart Isaacson, MD, director, Parkinsons Disease and Movement Disorder Center of Boca Raton

Stuart Isaacson, MD

Post-hoc data presented virtually at the European Academy of Neurology’s 6^th Congress suggest that istradefylline (Nourianz; Kyowa Kirin), patients with dyskinesia at baseline prior to starting treatment on the agent were more likely to experience dyskinesia as an adverse event (AE) during treatment than those without baseline dyskinesia.¹

Those on istradefylline 20-mg with baseline dyskinesia experienced an AE of dyskinesia at a rate of 24.7%, and the 40-mg group at a rate of 25.9%, compared to 14.1% of the placebo group with dyskinesia at baseline. Additionally, the istradefylline 20-mg and 40-mg groups without baseline dyskinesia had AE dyskinesia rates of 4.4% and 8.4%, respectively, compared to 3.5% in the placebo group.

Notably, though, both those with dyskinesia at baseline (n = 1515) and those without (n = 1204) treated with istradefylline experienced reductions in off time and an increase in on time without troublesome dyskinesia. The data were compiled by Stuart Isaacson, MD, director, Parkinson's Disease and Movement Disorders Center of Boca Raton, and colleagues.

"Uncontrolled, involuntary movements commonly known as dyskinesia can be very troublesome in patients with [Parkinson], especially those patients who experience ‘off’ episodes," Isaacson said in a statement.² "The results being presented at EAN suggest that dyskinesia is observed more often in patients with baseline dyskinesia before istradefylline was added to the treatment regimen and that the overall efficacy of istradefylline was not affected by patients' baseline status. We believe these data can be helpful to physicians as they make treatment decisions and may provide insight into the appropriate use of NOURIANZ in the treatment of 'off' time in patients with [Parkinson]."

Those who were on 20-mg and 40-mg istradefylline without dyskinesia at baseline (20 mg: n = 362; 40 mg: n = 419) experienced improvements in on time from baseline of 1.19 (±2.735) and 1.03 (±2.676) hours, respectively. These gains were from baseline hours of non-troublesome on time of 9.49 (standard deviation [SD], 2.454) and 9.50 (SD, 2.409). Those same participants on 20-mg had 6.87 hours (SD, 2.577) of off time at baseline, while those on 40-mg had 6.75 hours (SD, 2.430). Their respective reductions in off time were 1.29 hours (±2.6943) and 1.27 hours (±2.582).

Likewise, those who were on 20-mg and 40-mg istradefylline with dyskinesia at baseline (20 mg: n = 486 ; 40 mg: n = 460) experienced improvements in on time from baseline of 1.03 (±2.791) and 0.90 (±2.836) hours, respectively. Those on 20-mg had 5.71 hours (SD, 2.364) of on time at baseline, while those on 40-mg had 5.56 hours (SD, 2.178). They experienced reductions in off time of 1.18 hours (±2.394) and 1.17 hours (±2.459), respectively, from baseline.

Comparatively, those on placebo with dyskinesia (n = 423) and without dyskinesia (n = 569) at baseline had off times of 6.89 (SD, 2.350) and 5.81 (SD, 2.189) hours, respectively. Those placebo groups had mean reductions in off time of 0.80 (±2.337) and 0.79 (±2.703) hours, respectively. With regard to on time, at baseline, the placebo group with dyskinesia had 9.31 hours (SD, 2.558) and those without had 9.39 hours (SD, 2.425). Those improved by 0.73 (±2.739) and 0.62 (±2.658) hours, respectively.

“Dyskinesia as an AE was more frequent during istradefylline treatment, particularly in patients +BL-dyskinesia compared with —BL-dyskinesia patients. Istradefylline-induced improvements in off time and ON-WOTD time were not affected by the presence of baseline dyskinesia,” Isaacson and colleagues concluded.

The selective adenosine A2A receptor antagonist that acts via the indirect basal ganglia outflow pathway was approved by the FDA in August 2019, and became available to patients in October of that year.

In March, Isaacson spoke with NeurologyLive about how the challenge of treating off episodes is being addressed with combination therapy approaches and what treatments and delivery methods are available to combat absorption variation. Watch below to hear his perspective on how the current understanding of the disease and its medications is impacting physicians’ ability to reduce their patients’ OFF episodes.

REFERENCES

1. Isaacson SI, Ilattori N, Truong D, et al. Impact of baseline dyskinesia on the safety and efficacy of istradefylline, an adenosine A2A receptor antagonist, in patients with Parkinson’s disease: a pooled analysis of 8 clinical studies. Presented at: EAN Congress. Abstract EPO2206.

2. Impact of Baseline Dyskinesia on Safety and Efficacy of NOURIANZ® (istradefylline) in Patients with Parkinson's Disease Presented During "Virtual" European Academy of Neurology Meeting [press release]. Bedminster, NJ: Kyowa Kirin; Published May 26, 2020. Accessed June 4, 2020. prnewswire.com/news-releases/impact-of-baseline-dyskinesia-on-safety-and-efficacy-of-nourianz-istradefylline-in-patients-with-parkinsons-disease-presented-during-virtual-european-academy-of-neurology-meeting-301065566.html