26 April 2012 -
Brussels (Belgium), 1800 CET
Data presented at the 64th American Academy of Neurology (AAN) Annual Meeting
Insights into the effects of Neupro® (rotigotine transdermal system) on common non-motor symptoms of Parkinson’s disease (PD) were presented today at the 64th AAN Annual Meeting in New Orleans, USA.
A post-hoc analysis of data from five, randomized, double-blind, placebo-controlled trials investigated the effect of rotigotine transdermal system on neuropsychiatric features and fatigue in patients with PD. Improvements were observed with rotigotine transdermal system versus placebo in items assessing apathy, anhedonia, anxiety, anxiety/depression, depression and fatigue.1 In addition, a post hoc analysis of data from the RECOVER™* study investigated the effect of rotigotine transdermal system on pain in patients with PD, and in some patients with pain, improvements were observed with rotigotine transdermal system versus placebo.2
“Post hoc analyses of large amounts of data like these provide valuable insights into the potential impact of rotigotine on the everyday lives of people with Parkinson’s, and signal a need for further study in this area,”
said Professor Robert Hauser, Director, Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, FL.
Results presented below should be viewed in the context of the post-hoc analyses. In addition the p-values reported are exploratory and prospective studies are warranted to confirm these findings.
Summary of PD data presented at AAN 2012
ABSTRACT TITLE: Rotigotine transdermal system improves neuropsychiatric features (apathy, anhedonia, anxiety, and depression) and fatigue in patients with Parkinson’s disease: A post-hoc analysis of five double-blind placebo-controlled studies1
Post-hoc analysis of five placebo-controlled studies of rotigotine transdermal system in patients with early-PD (SP512, SP513), advanced-PD (PREFER, CLEOPATRA-PD), and PD with unsatisfactory control of early-morning motor symptoms (RECOVER™) was conducted*. Individual items assessing apathy, anhedonia, anxiety, anxiety/depression, depression and fatigue were identified from the scales used in these studies - the Non-Motor Symptoms Scale (NMSS), the Beck Depression Inventory (BDI-II), the 39-item Parkinson’s Disease Questionnaire (PDQ-39), the 8-item Parkinson’s disease questionnaire (PDQ-8) and the 5-item EuroQol Group questionnaire (EQ-5D).
Depression: Compared with placebo, improvements were observed with rotigiotine transdermal system in all 3 items assessing feelings of depression (p<0.02)
Anxiety/depression: Compared with placebo, improvements were observed with rotigotine transdermal system in the 1 item assessing anxiety/depression in 2 of 3 studies (p<0.03)
Anxiety: Compared with placebo, an improvement was observed with rotigotine transdermal system in 1 of 3 items assessing anxiety (p=0.002)
Apathy: Compared with placebo, improvements were observed with rotigotine transdermal system in all 3 items assessing apathy (p<0.04)
Anhedonia: Compared with placebo, improvements were observed with rotigotine transdermal system in 1 of 2 items assessing anhedonia (p=0.026)
Fatigue: Compared with placebo, improvements were observed with rotigotine transdermal system in 2 of 3 items assessing fatigue (p<0.003)
ABSTRACT TITLE: Rotigotine transdermal system improves pain in patients with Parkinson’s disease: A post-hoc analysis of patients reporting pain in the RECOVER study2
RECOVER™* (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine) was a double-blind, placebo-controlled study (n=287) that demonstrated significant improvements in early-morning motor function and nocturnal sleep disturbance with rotigotine transdermal system.* Secondary efficacy measures in the RECOVER™ study were the Nocturnal, Akinesia, Dystonia and Cramps Score (NADCS) and exploratory outcome measures included the Likert Pain Scale.3
For the post-hoc analysis, baseline Likert pain scores (0=no pain up to 10 =worst pain experienced) were available for 267 patients (89 placebo, 178 rotigotine). Seventy percent of patients had a score ≥1 (any pain) and of these, 47% scored 1-3 (mild pain), and 53% scored ≥4 (moderate to severe pain).
Improvements in pain were observed among patients with a score ≥1 at baseline with a treatment difference of -0.88 (p=0.0128), and in those with a score ≥4 with a treatment difference of -1.38 (p=0.0117). Treatment difference in the 1-3 sub-group was -0.37, (p=0.3756).
The Nocturnal Akinesia, Dystonia and Cramps Score (NADCS) was used to measure the severity of these symptoms, from 0 (normal) to 4 (maximal severity). In patients with a pain score ≥1, improvements were observed with rotigotine transdermal system versus placebo in NADCS with a treatment difference of -0.54 (p=0.0275). Treatment differences for 1-3 and ≥4 subgroups were -0.47 (p=0.1416), and -0.62 (p=0.0825).
* In SP513, PREFER, CLEOPATRA-PD and the RECOVER study patients received rotigotine transdermal system from 2-16 mg/24 hours. In the US the maximum recommended dosage of rotigotine transdermal system for patients with early-stage and advanced PD is 6 mg/24 hours and 8 mg/24 hours, respectively.
NOTES TO EDITORS
About Neupro® in the U.S.
Neupro® (Rotigotine Transdermal System) is indicated for the treatment of the signs and symptoms of idiopathic Parkinson’s disease and moderate-to-severe primary Restless Legs Syndrome (RLS). For more information about Neupro visit: www.neupro.com
Neupro® in the U.S. Important Safety Information
Neupro® contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people.
Patients treated with Neupro® have reported falling asleep while engaged in activities of daily living and somnolence. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for somnolence was 16% for early-stage Parkinson’s disease, 4% for advanced-stage Parkinson’s disease, and 6% for Restless Legs Syndrome. Some patients perceived no warnings signs, such as excessive drowsiness. Patients should be advised to exercise caution while driving, operating heavy machinery or working at heights during treatment with Neupro®.
There is an increased risk for hallucinations in patients with advanced-stage Parkinson’s disease treated with Neupro®. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for hallucinations was 4%, and this difference increased with increasing dose. Patients also may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during Neupro® treatment or after starting or increasing the dose of Neupro®.
Neupro® may cause symptomatic postural/orthostatic hypotension and syncope, especially during dose escalation, elevated blood pressure, elevated heart rate, weight gain and fluid retention. Neupro® should be used with caution in patients with severe cardiovascular disease.
Case reports suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and other intense urges, and the inability to control these urges while taking medications, including Neupro®, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease. Patients should be monitored for the development of new or increased urges while being treated with Neupro®. Dose reduction or discontinuation of Neupro® should be considered if such urges develop.
Neupro® may increase the dopaminergic side effects of levodopa and may cause and/or exacerbate pre-existing dyskinesia. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for dyskinesia was 7% for advanced-stage Parkinson’s disease, and this difference increased with increasing dose.
Neupro® can cause application site reactions, and some may be severe. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for application site reactions was 15% for early-stage Parkinson’s disease, 23% for advanced-stage Parkinson’s disease, and 39% for Restless Legs Syndrome. Most reactions were mild or moderate in intensity and were limited to the patch area.
Patients with Parkinson’s disease have a higher risk of developing melanoma than the general population. Patients should be monitored for melanomas frequently when using Neupro®.
Dopaminergic medicinal products, including Neupro®, may cause augmentation and rebound in RLS patients.
The most common adverse reactions (≥5% greater than placebo) for the highest recommended doses of Neupro® for treatment of Parkinson’s disease are nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, hyperhidrosis, and insomnia. The most common adverse reactions (≥5% greater than placebo) for the highest recommended dose of Neupro® for treatment of Restless Legs Syndrome are application site reactions, nausea, somnolence, and headache.
Additional important safety information for Neupro® can be accessed at: www.neupro.com/pi
About Neupro® in the European Union
Neupro® (rotigotine) is approved in the European Union for the treatment of the signs and symptoms of early-stage idiopathic Parkinson’s disease, as monotherapy (i.e. without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or on-off fluctuations). Neupro® is also approved in the European Union for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in adults.
Neupro® in the European Union Important Safety Information
Neupro® is contraindicated in case of hypersensitivity to the active substance or to any of its excipients, and in case of magnetic resonance imaging (MRI) or cardioversion. Neupro® should be removed if the patient has to undergo MRI or cardioversion to avoid skin
It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the risk of postural/orthostatic hypotension associated with dopaminergic therapy and reported during Neupro® treatment. Neupro® has been associated with somnolence and episodes of sudden sleep onset. Patients treated with dopamine agonists including Neupro®, have been reported pathological gambling, increased libido and hypersexuality. Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy. Therefore it is recommended to taper
Hallucinations have been reported, and patients should be informed that hallucinations can occur.
Cases of cardiopulmonary fibrotic complications have been reported in some patients treated with ergot-derived dopaminergic agents. Neuroleptics given as antiemetic should not be given to patients taking dopamine agonists. Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
External heat, from any source should not be applied to the area of the patch. Exposure of a skin rash or irritation to direct sunlight could lead to changes in the skin color. If a generalized skin reaction (e.g. allergic rash) associated with the use of Neupro® is observed, Neupro® should be discontinued.
Caution is advised when treating patients with severe hepatic impairment or acute worsening of renal function, a dose reduction might be needed.
The incidence of some dopaminergic adverse events, such as hallucinations, dyskinesia, and peripheral oedema generally is higher when given in combination with L-dopa. This should be considered when prescribing Neupro®.
Neupro® contains sodium metabisulphite, a sulphite that may cause allergic-type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people.
Neupro® should not be used during pregnancy. Breast-feeding should be discontinued.
In restless legs syndrome augmentation may occur. Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in severity of symptoms, and spread of symptoms to involve other body parts.
At the beginning of therapy, dopaminergic adverse reactions, such as nausea and vomiting, may occur. These are usually mild or moderate in intensity and transient, even if treatment is continued.
Adverse drug reactions reported in more than 10% of Parkinson’s patients treated with Neupro® are nausea, vomiting, application site reactions, somnolence, dizziness and headache. The majority of these application site reactions are mild or moderate in intensity.
Adverse drug reactions reported in more than 10% of RLS patients treated with Neupro® are nausea, application site reactions, asthenic conditions (including fatigue, asthenia, malaise) and headache. The majority of these application site reactions are mild or moderate in intensity.
All Neupro® supply should be stored in a refrigerator (2o C-8oC). There is no need for patients to transport Neupro® patches in special containers and they must not be stored in a freezer compartment.
Please refer to the European Summary of Product Characteristics for full prescribing information (Revised August 2011):
Hauser R, Nausieda P, Surmann E, Moran K, Barone P. Rotigotine transdermal system improves neuropsychiatric features (apathy, anhedonia, anxiety, and depression) and fatigue in patients with parkinson’s disease: A post-hoc analysis of five double-blind placebo-controlled studies. Presented at the American Academy of Neurology Annual Meeting, New Orleans, April 21-28 2012. Abstract number 500.
RECOVER study investigators. Rotigotine transdermal system improves pain in patients with Parkinson’s disease: A post-hoc analysis of patients reporting pain in the RECOVER study. Presented at the American Academy of Neurology Annual Meeting, New Orleans, April 21-28 2012. Abstract number 501.
Trenkwalder C, Kies B et al., Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: a double-blind, randomized, placebo-controlled study (RECOVER) 2011 Movement Disorders 26 (1), 90-99
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