Rotigotine transdermal patch benefits durable for restless legs syndrome
MedWire News: A rotigotine transdermal patch provides long-term symptom relief for patients with moderate-to-severe idiopathic restless legs syndrome, a 5-year study shows.
The study was an open-label extension of a 6-week randomized trial that demonstrated the efficacy, versus placebo, of a once-daily rotigotine transdermal patch, at a maximum dose of 4 mg/24 hours.
The average rotigotine dose taken by the study patients was 2·43 mg/24 h after 4 weeks of titration, and 3·09 mg/24 h by the end of the study, at which point 49% of patients were taking the maximum dose. Most dose adjustments happened during the first year.
A total of 295 patients entered the open-label phase, 126 of whom completed the 5-year study. The 169 patients who discontinued did so mostly because of adverse events (89 patients), as well as lack of efficacy (31 patients), and other reasons including withdrawal of consent, protocol deviations, and poor compliance.
Patients who completed the study achieved good control of symptoms, Diego García-Borreguero (Sleep Research Institute, Madrid, Spain) and colleagues report in The Lancet Neurology. Average total International Restless Legs Syndrome study group severity rating scale scores fell from 27.7 at enrollment to the double-blind trial to 9.0 at the end of the 5-year extension.
However, 23% of patients met Max Planck Institute (MPI) criteria for augmentation, with 13% meeting MPI criteria for clinically significant augmentation on at least one assessment.
Fifteen of the patients who had clinically significant augmentation were taking rotigotine at doses of 1-3 mg/24 h, which is the range approved by the European Medicines Agency, and 24 patients were taking the maximum 4 mg/24 h dose. Twelve patients discontinued treatment because of clinically significant augmentation.
Editorialist Christopher Earley (Johns Hopkins University School of Medicine, Baltimore, Maryland, USA) highlighted the problem of augmentation and the high rate of drop-out.
"If dopamine agonists fail after 5-10 years of use, what can be used for the remaining 10-30 years to manage the symptoms of restless legs syndrome?" he asked.
He said that the benefits provided by the rotigotine patch are "not unexpected," given that "virtually all" dopamine agonists to date have proved beneficial to patients with restless legs syndrome.
But he questioned the wisdom of the continued development of dopaminergic drugs, all of which were developed in models of Parkinson's disease, which bears little apparent relation to restless legs syndrome.
Earley concluded: "The findings raise important questions as to what we are treating with dopamine agonists, what we are not treating, and how we induce the pharmaceutical industry to think differently about restless legs syndrome and, thus, push development towards truly new and improved treatments."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Eleanor McDermid