Objective: The aim of this meta-analysis is to synthesize evidence about the efficacy of the adenosine receptor antagonists (Istradefylline and Preladenant) for patients with Parkinson’s disease.

Background: Multiple A2a receptor antagonists have been developed for the treatment of PD and their efficacy has been assessed in multiple clinical trials.

Methods: We searched PubMed through, November, 2015, using relevant keywords. Records were screened for relevant studies and data were extracted to online data extraction sheet and were analyzed. Outcomes of (off time, on time without troublesome dyskinesia, on time with troublesome dyskinesia, UPDRS III, and UPDRS II) were pooled as mean difference or weighted mean difference between the two groups from baseline to endpoints. Statistical analyses were conducted by RevMan version 5.3 for windows and Open[Meta-analyst].

Results: Ten RCTs (Istradefylline: 7 RCTs, n=2231; and Preladenant: 3 RCTs, n=1507 patients) were included. The overall effect estimate favored Istradefylline than placebo in terms of: (1) daily time off (20 mg/day: WMD -0.62, 95% CI -1.06 to -0.17; 40 mg/day: WMD -0.80, 95% CI -1.22 to -0.38); (2) on time without troublesome dyskinesia (20 mg/day: WMD 0.74, 95% CI 0.31 to 1.18; 40 mg/day: WMD 0.85, 95 % CI 0.40 to 1.31); and (3) UPDRS III “on state” (20 mg/day: WMD -0.91, 95% CI -1.71 to -0.11; 40 mg/day: WMD -1.61; 95 % CI -2.49 to -0.73). However, the overall effect estimate did not favor Istradefylline over placebo in terms of: (1) on time with dyskinesia (20 mg/day: WMD 0.89, 95% CI -0.66 to 2.44; 40 mg/day: WMD 0.98, 95 % CI -0.08 to 2.048); (2) UPDRS II during off state (20 mg/day: WMD -0.48, 95% CI -1.13 to 0.15; 40 mg/day: WMD -0.51, 95 % CI -1.30 to 0.26); and (3) UPDRS II during on state (20 mg/day: WMD 0.09, 95% CI -0.54 to 0.73); 40 mg/day: WMD -0.18, 95 % CI -0.49 to 0.11). For the Preladenant, the overall effect size favored Preladenant than Placebo in terms of “daily time off” and “on time without dyskinesia” but this effect size was not significant for the 2 mg, 5 mg, and 10 mg doses compared to placebo.

Conclusions: Istradefylline could improve the motor functions during the “on state” and it was effective in reducing the “off time” without increasing the “on time with troublesome dyskinesia”. Current evidence suggests that Preladenant can reduce the “off time”. However, further randomized controlled trials on Preladenant are needed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/istradefylline-and-preladenant-as-adjuvant-therapies-for-patients-with-parkinsons-disease/