Adenosine A2A Receptor Antagonist Istradefylline For Levodopa Induced Complications In Parkinson’s Disease

Objective:To assess the efficacy and safety of adjuvant istradefylline therapy versus placebo in PD patients with levodopa induced complications. And look forward to acquire the optimal dose of istradefylline through the subgroup analysis.Methods:We searched the Cochrane Movement Disorder Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, latest issue), MEDLINE (PubMed), EMBASE, China Biological Medicine Database (CBM-disc), Chinese National Knowledge Infrastructure Database (CNKI). Searched the abstracts of International Congress of Parkinson’s Disease and Movement Disorders conference proceedings of recent years. The date of search was from begining to April 2015. There were no language restrictions. Collect randomized controlled trials (RCTs) which compared istradefylline with placebo for levodopa induced complications in Parkinson’s Disease. Data analyzed by RevMan5.1 soft ware.Results:The 7 included trials recruited a total of 2231 participants,1552 patients received istradefylline,679patients received placebo. Meta-analysis showed that:(1) About effectiveness:compare with placebo, istradefylline was more likely to improve the awake time per day spent in the "OFF" state (MD=-0.60,95%CI [-0.91,-0.30]), motor impairment scores in ON state using UPDRS motor III (MD=-1.07,95%CI [-1.75,-0.39]). A subgroup analysis showed that:there was statistically significant istradefylline 20mg and 40mg improve the two outcome, awake time per day spent in the "OFF" state:20mg (MD=-0.60,95%CI [-1.04,-0.15]),40mg (MD=-0.78,95%CI [-1.20,-0.36]), motor impairment scores in ON state using UPDRS motor Ⅲ:20mg (MD=-1.02,95%CI [-2.04,0.00]),40mg (MD=-1.45,95%CI [-2.53,-0.37]), and there was no statistically significant Compare istradefylline 20mg with 40mg:awake time per day spent in the "OFF" state:MD= 0.17,95%CI [-0.23,0.56], motor impairment scores in ON state using UPDRS motor Ⅲ:MD = 0.90,95%CI [-0.32,2.11]. (2) About the safety:Istradefylline was more likely to increase of the total adverse events and dyslinesia (RR= 1.10,95%CI [1.04, 1.18]), (RR= 1.52,95%CI [1.19,1.93]). There was no significant differences in the occurrence of nausea and constipation and so on (RR= 1.37,95%CI [0.94,1.98]), (RR= 1.43,95%CI [0.90,2.27]). Compare istradefylline 20mg with 40mg, there was no significant differences in the occurrence of adverse events, total adverse events:RR= 1.02,95%CI [0.94,1.09]; dyslinesia:RR= 0.85,95%CI [0.60,1.20]; nausea:RR= 0.96,95%CI [0.47,1.95].Conclusion Istradefylline is effective in levodopa-induced complications in Parkinson’s disease. And istradefylline has a well tolerance and safety. Further high-quality randomized controlled trials are needed to provide reliable evidence on the treatment of patients with Parkinson’s disease.