Adenosine A2A receptor antagonist istradefylline 20 versus 40 mg/day as augmentation for Parkinson's disease: a meta-analysis

Background: Adenosine A2A receptor antagonist istradefylline 20 mg/day has been approved this year for manufacturing and market in Japan. Therefore, we did this meta-analysis to systematically evaluate the clinical applicability of 40 mg/day as augmentation to levodopa in patients with Parkinson's disease (PD). Method: Randomized controlled trials (RCT) that compared istradefylline with placebo for short-course treatment of PD in adults were systematically reviewed up to November 2013. Outcome measurements were daily off time and unified Parkinson's disease rating scale (UPDRS) Part III score (on state). Random-effect model was used. Result: Data were obtained from four RCTs. In these RCTs, 405 patients received istradefylline 20 mg/day and 420 patients received 40 mg/day. The pooled weighted mean difference was 0.17 with 95% confidence interval (CI) = [-20.23, 0.56] on daily off time and 0.70 with 95% CI = [-0.89, 2.29] on UPDRS Part III score (on state). The adverse events analysis showed that 20 and 40 mg/day had comparable acceptability. Heterogeneity was not existed. Conclusion: These results indicate that istradefylline 40 mg/day as augmentation shows potential promise on clinical applicability, and is worthy of further study. Limited by the number of included RCTs, future studies are needed to verify and support this conclusion, and assess the long-term effect of istradefylline, the effect of istradefylline as monotherapy and other dose of istradefylline.