In May, the FDA approved the rotigotine transdermal system (Neupro), the first skin patch for treating early-stage PD symptoms in the US. The patch has been available in Europe since March 2006. However, each of the experts was divided whether the new formulation is an improvement over existing dopamine agonists.
Rotigotine, a non-ergolinic dopamine agonist, is delivered continuously via a silicone-based skin patch 24 hours a day.
FDA approval was based on several studies funded by the patch manufacturer Schwarz; these randomized, double-blinded, and placebo-controlled studies included more than 1,500 patients with early-stage PD who were not taking other PD therapies. Two of these studies were published in Neurology.
One study found that the drug significantly improved Parkinson symptoms — as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) — in newly diagnosed patients who had little other drug therapy and were not taking levodopa-carbidopa or direct dopamine agonists (Neurology 2007;68:272–276).
The rotigotine group had more responders (48 percent) compared to placebo (19 percent), which was statistically significant (p<0.0001).
A second Neurology study (2007;68:1262–1267) found that rotigotine, as adjunctive therapy, demonstrated improvement in patients with more advanced PD, who were taking levodopa-carbidopa therapy but no other direct dopamine agonist. Compared to placebo, there were significant decreases in mean off-time of 1.8 hours per day for the rotigotine patch (at 8 mg daily) and 1.2 hour a day for the 12 mg patch. There was a greater than 30 percent responder rate in 55.6 percent of patients (with the 8 mg patch) and 55.1 percent (with the 12 mg patch) compared to 34.5 percent in the placebo group.
The rotigotine skin patch can be used for initial therapy or for adjunctive treatment with levodopa, as is true for pramipexole (Mirapex) and ropinirole (Requip), said Eric Ahlskog, PhD, MD, professor of neurology at Mayo Medical School and the chair of the Mayo-Rochester section of movement disorders in Rochester, MN.
“The drug is associated with all the expected adverse effects of dopamine agonists, but in no greater frequency than the currently available oral agents,” said Blair Ford, MD, associate professor of neurology at Columbia University.
Drs. Ahlskog and Ford cited several safety and efficacy concerns, including the high incidence of skin reactions that were common with the rotigotine patch, as well as daytime somnolence, which also occurs with pramipexole and ropinirole. “There is a high incidence of skin reactions to the patch, approaching 50 percent, but for most individuals, the reaction is mild, and does not lead to discontinuation of the treatment,” Dr. Ford said.
Dr. Ahlskog added that rotigotine's D3 receptor stimulation also may be responsible for the occasional pathological compulsive behaviors — such as gambling and hypersexuality — in some patients using adjunctive therapy of agonists like pramipexole and ropinirole.
Dr. Ford noted that the patch may help patients who have difficulty with oral medication. “For patients with dysphagia or problems with gastrointestinal absorption, and for pre-operative patients who can take nothing by mouth, the transdermal route may provide a significant advantage,” he said. “In addition, the once-a-day dosing schedule may improve patient compliance.”
Beyond its new formulation in a skin patch, however, rotigotine does not show an advantage over similar dopamine agonists like pergolide, ropinirole, and pramipexole, experts told Neurology Today.
William J. Weiner, MD, professor of neurology at the University of Maryland School of Medicine in Baltimore, pointed out that the patches might cause discomfort and skin irritation for some patients. “Neurologists should be aware that much of the discussion of continuous dopaminergic stimulation as a better mode of administration leading to improved efficacy is theoretical and not proven.”