Istradefylline Versus Opicapone for “Off” Episodes in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Abstract

Background: In recent times, the US-FDA approved istradefylline and opicapone as an adjunct to levodopa/carbidopa for managing the "off" episodes in Parkinson’s disease. Purpose: Current meta-analysis was performed to determine the safety and efficacy of these drugs in the management of “off” episodes and to recognize which among them would provide therapeutic benefits clinically. Methods: A thorough literature search was performed through the Cochrane Library, PubMed, and clinicaltrials.gov for a period from January 2003 to October 2020, with the following keywords: Istradefylline, KW-6002, opicapone, BIA 9-1067, and Parkinson’s disease. Those randomized, double-blind placebo/active comparator-controlled trials that analyzed the efficacy and safety of istradefylline and opicapone and that were published in the English language were included. In this analysis, the outcomes focused on the least square mean change in “off” time and Unified Parkinson’s Disability Rating Scale (UPDRS) III score from baseline to the end of the study, and the incidence of treatment-emergent adverse events (TEAEs) and dyskinesia. Results: Both drugs have shown significant reduction in “off” time duration (mean difference [MD] = –0.70; 95% CI [–1.11, –0.30]; P < 0.001 for istradefylline and MD = –0.85; 95% CI [–1.09, –0.61]; P < .001 for opicapone). Istradefylline showed significant improvement in UPDRS III (MD = –1.56; 95% CI [–2.71, –0.40]; P < .008), but the same was not observed with opicapone (MD = –0.63; 95% CI [–1.42, –0.15]; P < .12). The incidence of TEAEs and dyskinesia reportedly were higher in the intervention group rather than with the placebo, (risk ratio RR =1.11, 95% CI [1.02,1.20] for istradefylline and RR =1.12, 95% CI [1.00,1.25] for opicapone, and for dyskinesia particularly, the incidence was higher with opicapone as compared to istradefylline (RR = 3.47, 95% CI [2.17, 5.57], and RR = 1.77, 95% CI [1.29, 2.44], respectively). Conclusions: Both drugs were comparable in efficacy; however, istradefylline seemed to be better in reducing the UPDRS III score. Although the incidence of TEAEs and dyskinesia were higher with both the drugs, the incidence of dyskinesia was more in the opicapone group.

P2X7 Receptor and Purinergic Signaling: Orchestrating Mitochondrial Dysfunction in Neurodegenerative Diseases

“…However, the therapeutic effects begin to wane and are gradually outweighed by side effects such as on-off fluctuations with or without dyskinesia, clinically characterized by the absence and recurrence of motor symptoms with continued use of this combination ( Armstrong and Okun, 2020 ; Sahoo et al, 2020 ). In addition to existing therapies, researchers have suggested the inclusion of drugs aimed at inhibiting A2A purinergic receptors, which inhibit the amplification of signaling through A2A receptors and reduce signaling through D2 dopaminergic receptors ( Sahoo et al, 2020 ; Singh et al, 2021 ). These changes explain the positive effect of A2A receptor antagonists on enhancing motor function without progression of levodopa-induced dyskinesias ( Fuxe et al, 2015 ; Navarro et al, 2016 ).…”