Rasagiline for Parkinson's Disease May Alter Disease Course
S. Andrew Josephson

http://www.medscape.com/viewarticle/711123?src=rss

Posted: 11/30/2009; AccessMedicine from McGraw-Hill © 2009 The McGraw-Hill Companies




Current therapies for Parkinson’s disease (PD) have robust effects on symptoms (until the later stages of the disorder), but none has been proven to alter the course of the disease. Previous trials of multiple PD agents have failed to demonstrate this so-called neuroprotective effect. Rasagiline is ... often prescribed in the early stages of treatment...

The authors performed a double-blind trial of rasagiline versus placebo. In order to test whether rasagiline had neuroprotective effects, a delayed-start trial design was used... Conceptually, differences between treatment and placebo after the initial 36 weeks could be explained by effects on symptoms alone, disease modification, or both; however, changes that persist after the full 72 weeks, while all patients are receiving rasagiline, would likely be consistent with neuroprotective effects.

A total of 1176 patients with untreated PD were enrolled in the study...

In the group treated with 1 mg of rasagiline, all three primary endpoints were met, including a slower rate of worsening compared with placebo between weeks 12 and 36 (p = .01), less worsening between baseline and week 72 compared with placebo (p = .02), and noninferiority of the change in score between weeks 48 and 72 compared with the delayed-start group (p < .001). However, these three endpoints were not all met in the patients taking the 2-mg rasagiline dose. Although the 2-mg dose group did show less worsening between weeks 12 and 36 compared with placebo (p < .001), the change in total UPDRS score between baseline and week 72 was not significantly different from that in the delayed-start group (p = .60). Noninferiority was demonstrated in the change in score between weeks 48 and 72 compared with the delayed-start group (p < .001).

The results of this trial are somewhat confusing. Although rasagiline at a dose of 1 mg daily did seem to provide neuroprotective benefits, this was not replicated in the higher-dose group...
...It appears as if another trial will be needed to definitively determine if indeed a disease-modifying effect is present with rasagiline. In future trials, use of patients with more advanced disease may eliminate this possible confounder of symptomatic changes masking neuroprotective effects. Until that time, clinicians should consider the use of rasagiline for PD patients only in order to provide symptomatic benefit; alas, the elusive “holy grail” of neuroprotective effects in PD has not yet been found.