Abstract Details

Title Influence of Istradefylline Treatment on Levodopa Dose Escalation in PD Patients from over 10 Years of Experience

Topic Movement Disorders

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 5-001

Objective To evaluate the impact of istradefylline treatment on levodopa dosage in Japanese patients.

Background Istradefylline, a selective adenosine A_2A receptor antagonist, is indicated in the USA and Japan as adjunctive treatment to levodopa/decarboxylase inhibitors in adults with Parkinson’s disease (PD) experiencing OFF-time.

Design/Methods With data from a Japanese electronic health record database, interrupted time series analyses were used to compare gradients of escalating levodopa daily dosage (LDD) (mg/month) before and after istradefylline initiation in patients with PD. Data were analyzed by period relative to istradefylline treatment initiation (year 0): term 1 (years -6-0), term 2 (years 0-2), and term 3 (years 2-6). Subgroup analyses were performed based on LDD before istradefylline initiation (≥400 vs <400mg/day) and treatment with vs without dopamine agonists (DAs), monoamine oxidase-B inhibitors (MAO-BIs), or catechol-O-methyltransferase inhibitors (COMTIs) prior to istradefylline initiation.

Results The analysis included 4026 patients; median LDD at baseline was 400mg (IQR, 300-500). Among patients receiving ≥400mg/day levodopa or not receiving MAO-BIs or COMTIs prior to istradefylline treatment, there was a significant reduction in the gradient of LDD increase for term 3 vs 1 (≥400mg/day levodopa, -2.666, p=0.007; no MAO-BIs, -1.819, p=0.004; no COMTIs, -1.412, p=0.027). Patients not treated with DAs prior to istradefylline had a similar but non-significant trend.

Conclusions This real-world analysis of Japanese prescription data for patients with PD indicates that istradefylline decreased the gradient of LDD increase over time, suggesting that istradefylline drove suppression of levodopa dose escalation. This effect was most notable in patients already receiving >400 mg LD/day and was observed with long-term istradefylline treatment for more than two years. These findings suggest that istradefylline without other dopaminergic therapies may slow progressive LDD increases over time. Thus, initiating istradefylline before other levodopa adjunctive therapies may reduce the occurrence or severity of levodopa-induced complications, with potential pharmacoeconomic implications for PD.

Authors/Disclosures
Shinji Asada, Other (Kyowa Kirin) PRESENTER	Mr. Asada has received personal compensation for serving as an employee of Kyowa Kirin.
Nobutaka Hattori, MD, PhD, FANA (Juntendo University School of Medicine)	Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PARKINSON Laboratories Co., Ltd. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyowa Kirin Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TEIJIN PHARMA LIMITED.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sumitomo Dainippon Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Kyowa Kirin Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie GK. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd. . Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka Holdings Co.,Ltd.. Prof. Hattori has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai Co., Ltd. . Prof. Hattori has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sumitomo Dainippon Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharma Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis Pharma K.K.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for DAIICHI SANKYO Co., Ltd.. Prof. Hattori has received stock or an ownership interest from PARKINSON Laboratories Co., Ltd. The institution of Prof. Hattori has received research support from Japan Society for the Promotion of Science (JSPS). The institution of Prof. Hattori has received research support from Japan Agency for Medical Research and Development (AMED). The institution of Prof. Hattori has received research support from Japan Science and Technology Agency, Health Labour Sciences Research Grant. The institution of Prof. Hattori has received research support from Japan Science and Technology Agency (JST). The institution of Prof. Hattori has received research support from Kyowa Kirin Co.,Ltd.. The institution of Prof. Hattori has received research support from Medtronic, Inc.. The institution of Prof. Hattori has received research support from Boston Scientific Corporation. The institution of Prof. Hattori has received research support from TEIJIN PHARMA LIMITED.. The institution of Prof. Hattori has received research support from AbbVie GK. The institution of Prof. Hattori has received research support from FP Pharmaceutical Corporation. The institution of Prof. Hattori has received research support from Dai-Nippon Sumitomo Pharma Co.,Ltd. The institution of Prof. Hattori has received research support from Nihon Medi-physics Co.,Ltd.,. The institution of Prof. Hattori has received research support from Eisai Co.,Ltd. . The institution of Prof. Hattori has received research support from Kirin Holdings Company, Limited. The institution of Prof. Hattori has received research support from Mitsubishi UFJ Trust and Banking Corporation. The institution of Prof. Hattori has received research support from GLORY LTD.. The institution of Prof. Hattori has received research support from Nippon Life Insurance Company. The institution of Prof. Hattori has received research support from Otsuka Pharmaceutical, Co.,Ltd. The institution of Prof. Hattori has received research support from AbbVie GK,. The institution of Prof. Hattori has received research support from Meiji Seika Pharma Co., Ltd.. The institution of Prof. Hattori has received research support from Ono Pharmaceutical Co., Ltd.. The institution of Prof. Hattori has received research support from FUJIFILM Wako Pure Chemical Corporation. The institution of Prof. Hattori has received research support from Sunwels,Inc.. The institution of Prof. Hattori has received research support from OHARA Pharmaceutical Co.,Ltd.. The institution of Prof. Hattori has received research support from PARKINSON Laboratories Co., Ltd.. The institution of Prof. Hattori has received research support from Ono Pharmaceutical Co., Ltd.. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Team Leader with RIKEN Center for Brain Science. Prof. Hattori has received personal compensation in the range of $500-$4,999 for serving as a Program officer with AMED: Japan Agency for Medical Research and Development.
	No disclosure on file
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Akihisa Mori, PhD (SNLD, Ltd.)	Mr. Mori has received personal compensation for serving as an employee of SNLD, Ltd., Japan.

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