Safety and effectiveness of istradefylline in patients with Parkinson’s disease: interim analysis of a post-marketing surveillance study in Japan

Abstract

Background: Istradefylline is a first-in-class, non-dopaminergic, selective adenosine A 2A receptor antagonist for the treatment of Parkinson's disease (PD) in patients experiencing the wearing-off phenomenon with levodopa (L-DOPA). The authors present an interim report from a post-marketing surveillance (PMS) evaluating the safety and effectiveness of long-term istradefylline in a real-world setting.Research design and methods: Istradefylline safety was assessed by the incidence of adverse events (AE) and adverse drug reactions (ADRs). Effectiveness was assessed using the physician's assessment of off-time, off-time symptoms and motor dysfunction, unified PD rating scale (UPDRS) Part III score, and the physician's global assessment.Results: This analysis evaluated 476 patients. Istradefylline was generally well tolerated, despite dyskinesia and hallucination being the most common ADRs. Reduction in off-time was observed in 38.2% of patients, off-time symptoms were improved or markedly improved in 44.7%, and motor dysfunction was improved or markedly improved in 48.5%. The mean UPDRS Part III score decreased from 33.7 to 30.3 at the end of the study. The physician's global assessment rated the drug as effective in 61.3% of patients. Conclusions: This PMS provides useful safety and effectiveness data for long-term treatment with istradefylline in a real-world setting for patients with PD exhibiting the wearing-off phenomenon with L-DOPA. ARTICLE HISTORY

Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson’s Disease: A New Therapeutic Strategy

“…In the last years, a considerable number of drugs that do not have DA activity have emerged and have been tested in clinical phases in an attempt to control the motor fluctuations (on-off phases) related with PD (for a review see [23]) and importantly, to deliver novel disease-modifying therapies. On the one hand, adenosine A 2A antagonists (istradefylline, preladenant, and tozadenant (NCT02453386)) have been proposed because adenosine participates in the onset of motor misbalance [24][25][26][27][28]. Istradefylline is another A 2A antagonist that has been approved as add-on therapy by the FDA in 2019 (NCT01968031).…”

Synthesis and Structure Activity Relationships of Chalcone based Benzocycloalkanone Derivatives as Adenosine A1 and/or A2A Receptor Antagonists

“…Prepared as for 2a from 4-hydroxy-1-indanone (0.500 g, 3.375 mmol) and 4-hydroxybenzaldehyde (0.412 g, 3.375 mmol) to yield 2b as brown powder (0.690 g, 81 %): Rf: 0.13 (DCM/EtOAc 10:1); mp: 276. 3…”

“…Furthermore, the first in class selective A 2A AR antagonist, istradefylline (1a) has been approved for manufacturing and marketing as Nouriast ® in Japan only since 2013 as a novel antiparkinsonian agent for wearing-off phenomena associated with levodopa treatment [2]. A post-marketing surveillance study conducted in Japan proved istradefylline (1a) safe and effective; it is generally well tolerated, despite dyskinesias and hallucinations as common adverse effects [3]. Recently, the USFDA approved istradefylline (1a) as add-on drug to treat off episodes in adults with Parkinson's disease (PD) [4].…”

Common Myths and Misconceptions That Sidetrack Parkinson Disease Treatment, to the Detriment of Patients

“…The newly approved adenosine A 2a antagonist istradefylline has modest benefits as an adjunct to carbidopa/ levodopa compared with placebo but with limited overall efficacy. 4,5 Amantadine has mild symptomatic PD benefit but with utility primarily restricted to attenuation of levodopa-induced dyskinesia. 6,7 These other medications will not be discussed further in this article.…”