Real-world evidence on levodopa dose escalation in patients with Parkinson's disease treated with istradefylline
- PMID: 38134023
- PMCID: PMC10745149
- DOI: 10.1371/journal.pone.0269969
Real-world evidence on levodopa dose escalation in patients with Parkinson's disease treated with istradefylline
Abstract
Objective: Istradefylline, a selective adenosine A2A receptor antagonist, is indicated in the US and Japan as adjunctive treatment to levodopa/decarboxylase inhibitors in adults with Parkinson's disease (PD) experiencing OFF time. This study aimed to observe patterns of dose escalation of levodopa over time in patients initiated on istradefylline.
Methods: Using Japanese electronic health record data, interrupted time series analyses were used to compare levodopa daily dose (LDD, mg/day) gradients in patients before and after initiation of istradefylline. Data were analyzed by period relative to istradefylline initiation (Month 1): pre-istradefylline (Months -72 to 0), early istradefylline (Months 1 to 24), and late istradefylline (Months 25 to 72). Subgroup analyses included LDD before istradefylline initiation (<400, ≥400 to <600, ≥600 mg/day) and treatment with or without monoamine oxidase-B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, or dopamine agonists before istradefylline initiation.
Results: The analysis included 4026 patients; mean (SD) baseline LDD was 419.27 mg (174.19). Patients receiving ≥600 mg/day levodopa or not receiving MAO-B inhibitors or COMT inhibitors demonstrated a significant reduction in LDD increase gradient for pre-istradefylline vs late-phase istradefylline (≥600 mg/day levodopa, -6.259 mg/day each month, p<0.001; no MAO-B inhibitors, -1.819 mg/day each month, p = 0.004; no COMT inhibitors, -1.412 mg/day each month, p = 0.027).
Conclusions: This real-world analysis of Japanese prescription data indicated that slowing of LDD escalation was observed in patients initiated on istradefylline, particularly in those receiving ≥600 mg/day levodopa, suggesting istradefylline may slow progressive LDD increases. These findings suggest that initiating istradefylline before other levodopa-adjunctive therapies may mitigate LDD increases, potentially reducing occurrence or severity of levodopa-induced complications in long-term istradefylline treatment.
Copyright: © 2023 Hattori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Conflict of interest statement
I have read the journal’s policy and the authors of this manuscript have the following competing interests: NH: Research funding from AbbVie, Asahi Kasei Medical, Astellas, Boston Scientific, Daiichi Sankyo, Dai-Nippon Sumitomo, Eisai, FP Pharmaceutical, Kyowa Kirin, Medtronic, Mitsubishi Tanabe, MiZ, Nihon Medi-Physics, Nihon Pharmaceutical, Nippon Boehringer Ingelheim, OHARA, Ono Pharmaceutical, Otsuka, Takeda; consulting for Dai-Nippon Sumitomo; advisory boards for Dai-Nippon Sumitomo, Kyowa Kirin, Otsuka, Sanofi, Takeda; subcontracting (trial cases) for Biogen Japan, Hisamitsu, Meiji Seika; contract research for Biogen Japan, Mitsubishi Tanabe; honoraria from AbbVie, Alexion, Boston Scientific, Daiichi Sankyo, Dai-Nippon Sumitomo, FP Pharmaceutical, Kyowa Kirin, Lundbeck Japan, Medtronic, MSD K.K., Mylan, Nippon Boehringer Ingelheim, Novartis, Otsuka, Pfizer Japan, Takeda. DK: Honoraria for statistical analysis, consulting, and lecturing from Kyowa Kirin Co., Ltd. SA, TK, TN & AM: Employment with Kyowa Kirin Co., Ltd. AS: Honoraria for statistical analysis, consulting, and lecturing from Kyowa Kirin Co., Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Figures
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