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The Rotigotine Patch for Early Parkinson's Disease
Abstract and Commentary
By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg receives research support from Boehringer-Ingelheim.
Synopsis: The rotigotine transdermal system (Neupro) is a safe and effective treatment for early Parkinson's Disease.
Source: Jankovic J, et al. Transdermal Rotigotine: Double-blind, Placebo-Controlled Trial in Parkinson Disease, Arch Neurol. 2007; 64(5): 676-682.
Dopamine agonists have played a key role in the treatment of Parkinson's Disease (PD) for many years, but until recently were only available in the United States as oral medications that needed to be taken several times daily. This pharmaceutical-sponsored randomized, double-blind, multicenter, placebo-controlled trial examined the safety and efficacy of the rotigotine transdermal system (Neupro), a non-ergolinic dopamine agonist medication delivered via a 24-hour cutaneous patch, in the treatment of early PD. The primary outcome measure was the "20% responder rate," defined as the percentage of subjects who achieved a 20% reduction (improvement) in the sum of the activities of daily living (part II) and motor (part III) subsets of the Unified Parkinson's Disease Rating Scale (UPDRS).
A total of 277 subjects with early PD (5 years duration) who were not on dopaminergic therapy were randomized in a 2:1 ratio to receive either rotigotine (n=181) or placebo (n = 96). Subjects were recruited from fifty sites in the United States and Canada. There was a 3-week flexible-dose titration phase, followed by 24 weeks of maintenance therapy with either rotigotine or placebo. The maintenance dose of rotigotine was either 2, 4, or 6 mg/24 hours based on optimal clinical response (mean = 5.7 mg/24 hours).
At the end of the maintenance phase, the rotigotine-treated group had a significantly greater 20% responder rate than the placebo group (48% vs 20% of subjects, p < 0.001). Several secondary endpoints, including the percentage change in the sum of the UPDRS part II and III scores (-15.1% vs. 7.3%, p < 0.001) and the percentage of patients who demonstrated clinical improvement on the Clinical Global Impression Scale (57% vs. 30%, P < 0.001) were also improved in the rotigotine vs. placebo group. The sum of the UPDRS part II and III scores improved by about 4 points in the rotigotine group vs. a 1.3 point worsening in the placebo group (p < 0.05). The most common adverse event was application site reaction (usually mild or moderate in severity), which occurred in 44% of patients who received rotigotine vs. 12% of those who received placebo. Other common adverse effects included nausea (41% vs. 17% in the placebo group) and somnolence (33% vs. 20% in the placebo group).
The recently FDA-approved rotigotine patch is a welcome new addition to the armamentarium of treatment options for early Parkinson's disease. The mechanism of action of rotigotine is comparable to that of oral dopamine agonists, but the 24-hour transdermal patch is a novel delivery system that allows for treatment of patients who cannot take oral medications, can be administered independent of mealtimes, and has the potential to increase patient adherence. The absolute improvement in UPDRS scores was small but significant, and clinically relevant as reflected by the Clinical Global Impression Scale. Physicians who use this medication should be aware of the high frequency of application site reactions, and that transdermal administration does not eliminate the nausea that commonly occurs with this class of medications. Further studies are needed to determine whether the more continuous dopamine receptor stimulation provided by this medication may reduce susceptibility to motor complications such as wearing off and dyskinesias.