Rasagiline Slows Functional Decline in Patients With Parkinson's: Presented at ANA

By Andrew N. Wilner, MD

SALT LAKE CITY, Utah -- September 24, 2008 -- Early treatment with rasagiline 1 mg slows functional decline in patients with Parkinson's disease, according to research presented here at the American Neurological Association (ANA) 133rd Annual Meeting.

The ADAGIO delayed-start trial was the first prospectively-designed clinical trial to test the potential of rasagiline to delay the progression of Parkinson's disease.

Rasagiline is a selective, irreversible, second-generation monoamine oxidase B inhibitor and may possess neuroprotective properties, possibly due to its propargyl moiety, said Warren Olanow, MD, Mount Sinai School of Medicine, New York, New York.

"Neuroprotection is the holy grail of treatment for Parkinson's disease," Dr. Olanow observed in a presentation on September 23. "Symptoms such as falling, freezing, and dementia are nondopaminergic and a major cause of disability in the later stages of Parkinson's disease. We need neuroprotective therapies to address these symptoms."

For their study, Dr. Olanow and colleagues enrolled 1,176 patients with early, previously untreated Parkinson's disease. Diagnosis was based on the presence of resting tremor, bradykinesia, or rigidity. The study used a delayed-start design with 4 treatment arms: rasagiline 1 or 2 mg/day for 72 weeks (early start) or placebo for 36 weeks followed by rasagiline 1 or 2 mg/day for 36 weeks (delayed start).

At the end of the first, double-blind, placebo-controlled, 36-week phase, if there were a difference in outcome as measured by the Total Unified Parkinson's Disease Rating Scale (UPDRS), the placebo group would be switched to rasagiline.

Results at the end of 36 weeks show a significant benefit with rasagiline 1 mg compared with placebo in the UPDRS score as measured by the slope of rasagiline minus the slope of placebo = -0.05 (P = .0133). At that time, the placebo patients were switched to rasagiline 1 mg and both groups were followed for another 36 weeks.

At the end of 72 weeks, the early rasagiline group maintained its superiority. Further, there was noninferiority of the slopes of the 2 active-treatment groups, which suggests that the group that began treatment late could not catch up to the benefits achieved in UPDRS by the early treated group.

With rasagiline 2 mg, there was significant benefit at the end of 36 weeks compared to placebo. However, at the end of an additional 36 weeks, both groups had similar efficacy, suggesting there was no advantage of starting rasagiline 2 mg early. Dr. Olanow acknowledged that there was not a ready explanation why the 1 mg dose but not the 2 mg dose demonstrated persistent superiority to the late- start treatment.

Dr. Olanow concluded, "Early treatment with rasagiline 1 mg provides a benefit that cannot be achieved with later introduction of the same drug. This may be evidence of neuroprotection or preservation or enhancement of supportive, compensatory mechanisms."