Rasagiline for Motor Fluctuations in the Elderly with Parkinson's Disease

Abstract & Commentary

By Claire Henchcliffe, MD, Associate Professor of Neurology and Neuroscience, Weill Cornell Medical College. Dr. Henchcliffe reports she is on the speakers bureau and advisory board for Allergan and Teva; speakers bureau for Boehringer-Ingelheim, GlaxoSmithKline, and Novartis; advisory board for Merz; and is a consultant for Gerson Lehman Group and Guidepoint Global.

Synopsis: In a post-hoc analysis, rasagiline, as an adjunct to levodopa, is both efficacious in reducing "off" time and well-tolerated in individuals older than 70 years with moderate-to-advanced Parkinson's disease.

Source: Tolosa E, Stern M. Efficacy, safety and tolerability of rasagiline as adjunctive therapy in elderly patients with Parkinson's disease. Europ J Neurol 2012;19:258-264.

This post-hoc analysis pooled data from two large Phase 3 clinical trials testing rasagiline as adjunctive therapy to levodopa, and sought to examine efficacy, safety, and tolerability in elderly vs younger subjects (≥ 70 vs < 70 years). The trials were (1) PRESTO: 26 weeks duration, rasagiline 0.5 mg daily and 1 mg daily vs placebo; and (2) LARGO: 18 weeks duration, rasagiline 1 mg daily vs placebo; entacapone treatment as comparator. Of 768 pooled subjects, 216 individuals were > 70 years, and mean age in the younger vs elderly cohort treated with rasagiline was 59.9 ± 7.0 vs 74.6 ± 3.6 years. Use of dopamine agonists was higher in the younger group (67.9 vs 55.9%) but other concomitant medications are not reported. Primary efficacy endpoint was reduction in mean total daily "off" time, which was numerically slightly better in the elderly group (-1.41 h rasagiline vs -0.43 h placebo, P < 0.01) than in the younger group (-1.43 h rasagiline vs -0.7 h placebo, P < 0.001). The elderly group experienced an increase of 0.58 h (rasagiline) vs 0.25 h (placebo) "on" time without troublesome dyskinesias, but an increase in "on" time with troublesome dyskinesias from 0.18 h (baseline) to 0.72 h in the elderly group (nonsignificant increase in the younger group). Rasagiline was well tolerated in both groups. With one adverse event of particular concern in elderly patients, hallucinations occurred in 6.5% of the elderly vs 1.7% of the younger group.


As the population ages, it is imperative that therapeutic testing be addressed in the elderly. This is particularly important as the elderly are more at risk from drug-associated side effects, particularly if cognitive deficits or other age-related medical illnesses are present. "Wearing off" of levodopa effect at the end of dose is often disabling and distressing to the patient. Management options include the MAO-B inhibitors rasagiline and selegiline, dopamine agonists, catechol-O-methyltransferase inhibitors, and in some cases, deep brain stimulation therapy. For the most part, there are few evidence-based guidelines in the elderly population. Despite the limitations of post-hoc analyses, therefore, this data mining approach offers valuable information supporting the use of rasagiline as an adjunct to levodopa for reduction in "wearing off" in those over 70 years old. Furthermore, although there were more adverse events in this cohort, it had a good tolerability profile overall. Their data do not allay concerns over increasing "on" time with troublesome dyskinesias, and this occurred more frequently in the elderly vs younger subjects: attention will still need to be paid to appropriate adjustment in levodopa-based medications. Unfortunately, data on other medications are lacking and it is possible that the younger patients were more likely to take amantadine, which has antidyskinetic properties. This study does not replace a properly powered prospective trial aimed at answering the question of safety and efficacy of rasagiline in the elderly. Nor does it include data broken down by decade (for example, it would be desirable to see data in the > 75 or > 80 year olds). However, it emphasizes that future studies need to include older patients with Parkinson's disease, and does provide some initial data to physicians treating older individuals.