Abstract Details

Title Comparative Safety of Istradefylline Among Parkinson’s Disease Adjunctive Therapies: A Systematic Review and Meta-analysis of Randomized Controlled Studies

Topic Movement Disorders

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-017

Objective

To evaluate the safety of istradefylline vs. other PD adjuncts based on randomized controlled trials (RCTs) available at the time of US approval.

Background

Istradefylline has demonstrated a significant reduction in “OFF” time when used as an adjunct to levodopa/carbidopa in patients with Parkinson’s Disease (PD).

Design/Methods

A systematic review (SR) published in 2011 was updated with additional RCTs 1/1/2010-4/15/2019 of dopamine agonists (DAs), catechol-O-methyl transferase (COMT) inhibitors, monoamine oxidase type B (MAO-B) inhibitors, amantadine, and istradefylline as adjuncts to levodopa. Pair-wise meta-analysis and Bucher indirect comparisons were used to generate estimates of relative safety. Results are presented as OR [95% CI].

Results Among 64 RCTs eligible for inclusion across the original (n=44) and updated (n=20) SRs, 57 RCTs involving 11,517 patients were included for meta-analysis. Istradefylline data were extracted from clinical study reports. At 40 mg, istradefylline demonstrated significantly lower odds of dyskinesia and somnolence compared to DAs (1.30 [1.01, 1.69] and 2.50 [1.28, 5.00], respectively) and lower odds of hypotension compared to MAO-B inhibitors (8.33 [1.67, 50.00]). At 20 mg, the odds of dyskinesia were significantly lower for istradefylline vs. COMT inhibitors (1.52 [1.09, 2.13]), DAs (1.61 [1.16, 2.22]), and all interventions (1.45 [1.06, 2.00]). Relative to istradefylline, amantadine had significantly increased odds of hallucinations (40mg: 3.57 [1.30, 10.00]; 20mg: 4.76 [1.64, 14.29]) vs. istradefylline at 40 and 20mg, and insomnia and withdrawals due to treatment emergent adverse events (TEAEs) at 20mg (8.33 [1.06, 50.00] and 2.86 [1.18, 6.67], respectively). The odds of overall incidence of TEAEs including constipation, dyskinesia, hallucination, hypotension, insomnia, orthostatic hypotension, and somnolence were significantly lower for istradefylline compared with COMT inhibitors (40mg: 1.33 [1.03, 1.75]; 20mg: 1.32 [1.01, 1.72]) and amantadine (40mg: 3.45 [1.85, 6.25]; 20mg: 3.33 [1.82, 6.25]).

Conclusions Istradefylline is associated with a generally favorable safety profile relative to others adjunct medications in this study.

Authors/Disclosures
Joyce Z. Qian, PhD (Kyowa Kirin, Inc.) PRESENTER	Dr. Qian has received personal compensation for serving as an employee of Kyowa Kirin, Inc..
Yasar A. Torres-Yaghi, MD	Dr. Torres-Yaghi has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda. Dr. Torres-Yaghi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Torres-Yaghi has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Amneal. Dr. Torres-Yaghi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Abbott. Dr. Torres-Yaghi has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Kyowa Kirin. Dr. Torres-Yaghi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Dr. Torres-Yaghi has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sunovion .
Hannah Cummings, PhD	Dr. Cummings has received personal compensation for serving as an employee of Kyowa Kirin.
Hiroo Shimoda	Hiroo Shimoda has received personal compensation for serving as an employee of Kyowa Kirin Co., Ltd..
Satoru Ito (Kyowa Kirin Co., Ltd.)	No disclosure on file
Sarah Batson (Mtech Access)	No disclosure on file
Stephen Mitchell (Mtech Access)	Stephen Mitchell has nothing to disclose.
Fernando L. Pagan, MD, FAAN (Georgetown University Hospital Dept of Neurology)	Dr. Pagan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acorda. Dr. Pagan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Adamas. Dr. Pagan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amneal. Dr. Pagan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merz. Dr. Pagan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kyowa Kirin. Dr. Pagan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sunovion. Dr. Pagan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Pagan has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for US World Meds. Dr. Pagan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Supernus. Dr. Pagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Pagan has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Acorda. Dr. Pagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Adamas. Dr. Pagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amneal. Dr. Pagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sunovion. Dr. Pagan has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Teva. Dr. Pagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurocrine. Dr. Pagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sunovion. Dr. Pagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Supernus. Dr. Pagan has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Parkinsonism and related Disorders. Dr. Pagan has stock in Keiferx. The institution of Dr. Pagan has received research support from US World Meds. The institution of Dr. Pagan has received research support from Novartis.

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