Abstract Details

Title Comparative Safety of Istradefylline in Parkinson’s Disease: A Systematic Review of Randomized Controlled Trials and Real-world Studies

Topic Movement Disorders

Presentation(s) P7 - Poster Session 7 (5:00 PM-6:00 PM)

Poster/Presentation
Number 5-016

Objective

To assess the relative safety of istradefylline vs. other Parkinson’s Disease (PD) adjuncts based on randomized controlled trials (RCTs) and real-world evidence (RWE).

Background

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

Design/Methods

A systematic search for studies published until January 1^st, 2024 was conducted. Relative safety was estimated using a Bayesian network meta-analysis (NMA) of RCTs and presented as OR [95% credible interval (CrI)]. Random and fixed-effect models were explored for all outcomes. Inconsistency was assessed through loop-specific approach and heterogeneity was evaluated by global I² statistic and between-study heterogeneity. Incidence rates of safety outcomes were summarized from RWE.

Results

A total of 100 RCTs and 55 RWE publications met the predefined inclusion criteria, and 76 RCTs (n=22,967 patients) were included in NMA. Istradefylline demonstrated lower odds of hallucination (OR=0.25 [95%CrI: 0.06, 0.97]), treatment-emergent AEs (0.43 [0.25, 0.73]), treatment-related AEs (0.33 [0.19, 0.56]), serious AEs (0.56 [0.32, 0.99]), and withdrawals due to AEs (0.37 [0.19, 0.68]) vs. amantadine. Istradefylline demonstrated lower odds of hypotension vs. catechol-O-methyl transferase inhibitors (COMTis) (0.19 [0.03, 0.82]) and monoamine oxidase type B inhibitors (MAO-Bis) (0.09 [0.01, 0.52]), lower odds of dyskinesia (0.63 [0.40, 0.99]) vs. COMTis, and lower odds of nausea (0.57 [0.33, 0.99]) vs. dopamine agonists (DAs). In a sensitivity analysis of RCTs after year 2000, there was a reduction in the odds of dyskinesia (0.55 [0.38, 0.82]) and hallucination (0.41 [0.16, 1.00]) for istradefylline vs. DAs. RWE data were heterogenous but indicate that istradefylline displayed a lower incidence of dyskinesia compared with MAO-Bis, somnolence compared with DAs and COMTis, nausea compared with all comparators, and peripheral edema and hallucinations compared with amantadine.

Conclusions

Overall, istradefylline exhibits a favorable safety profile compared to other PD adjunct therapies, as demonstrated by both RCTs and RWE.

Authors/Disclosures
Sagari R. Bette, MD (Parkinson's Disease and Movement Disorders Center of Boca Raton) PRESENTER	Dr. Bette has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amneal. Dr. Bette has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amneal. Dr. Bette has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyowa Kirin. Dr. Bette has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merz. Dr. Bette has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Supernus. Dr. Bette 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. Bette has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Merz. Dr. Bette has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Supernus.
Joyce Z. Qian, PhD (Kyowa Kirin, Inc.)	Dr. Qian has received personal compensation for serving as an employee of Kyowa Kirin, Inc..
Hannah Cummings, PhD	Dr. Cummings has received personal compensation for serving as an employee of Kyowa Kirin.
Katsumi Shinoda, PhD (Kyowa Kirin Co., Ltd.)	Dr. Shinoda has received personal compensation for serving as an employee of Kyowa Kirin Co., Ltd..
Hiroo Shimoda	Hiroo Shimoda has received personal compensation for serving as an employee of Kyowa Kirin Co., Ltd..
Ashley Thai, MD	Dr. Thai has received personal compensation for serving as an employee of Kyowa Kirin.
Sarah Batson (Mtech Access)	No disclosure on file
Stephen Mitchell (Mtech Access)	Stephen Mitchell has nothing to disclose.
Gabrielle Redhead (Mtech Access)	Gabrielle Redhead has nothing to disclose.
Daniel D. Truong, MD, FAAN (PMDI)	The institution of Dr. Truong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Supernus. The institution of Dr. Truong has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Amneal. The institution of Dr. Truong has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Neurocrine Biosciences. The institution of Dr. Truong has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. The institution of Dr. Truong has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Truong has received research support from Abbvie. The institution of Dr. Truong has received research support from Aeon. The institution of Dr. Truong has received research support from Biogen. The institution of Dr. Truong has received research support from Bukwang. The institution of Dr. Truong has received research support from Cerevel. The institution of Dr. Truong has received research support from Eli Lilly. The institution of Dr. Truong has received research support from Enterin. The institution of Dr. Truong has received research support from Ipsen. The institution of Dr. Truong has received research support from Lundbeck. The institution of Dr. Truong has received research support from Neurocrine. The institution of Dr. Truong has received research support from Neuroderm. The institution of Dr. Truong has received research support from Parkinson Foundation. The institution of Dr. Truong has received research support from Prilenia. The institution of Dr. Truong has received research support from Revance. The institution of Dr. Truong has received research support from Sunovion. Dr. Truong has received publishing royalties from a publication relating to health care. Dr. Truong has received publishing royalties from a publication relating to health care. Dr. Truong has a non-compensated relationship as a President with International Association for Parkinsonism and Related Disorders that is relevant to AAN interests or activities.

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