Istradefylline for OFF Episodes in Parkinson's Disease: A US Perspective of Common Clinical Scenarios

Abstract

The effective management of OFF episodes remains an important unmet need for patients with Parkinson's disease (PD) who develop motor complications with long-term levodopa therapy. Istradefylline is a selective adenosine A_2A receptor antagonist for the treatment of patients with PD experiencing OFF episodes while on levodopa/decarboxylase inhibitor. Originally approved in Japan, istradefylline was recently approved in the USA. In this article, we provide a specific review of the four clinical studies that the FDA included in the approval of istradefylline in the USA, and discuss common clinical scenarios, based on our experience, where treatment with istradefylline may benefit patients experiencing motor fluctuations.

Keywords: A2A receptors; OFF time; Parkinson’s disease; adenosine; istradefylline; motor fluctuations; treatment.

Figure 1

Reduction in OFF time and increases in good ON time (ON without troublesome dyskinesia) from the four randomized controlled studies (istradefylline versus placebo) that led to FDA approval. Study 1, 6002-US-005; Study 2, 6002-US-013; Study 3, 6002-0608; Study 4, 6002-009.

Figure 2

Summary of efficacy outcomes from the four randomized controlled studies (istradefylline versus placebo) that led to FDA approval. Study 1, 6002-US-005; Study 2, 6002-US-013;40 Study 3, 6002-0608; Study 4, 6002-009.