Rotigotine transdermal system and evaluation of pain in patients with Parkinson’s disease: a post hoc analysis of the RECOVER study

BMC Neurology, Mar 2014

Background Pain is a troublesome non-motor symptom of Parkinson’s disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system. Improvements were also reported on a Likert pain scale (measuring any type of pain). This post hoc analysis of RECOVER further evaluates the effect of rotigotine on pain, and whether improvements in pain may be attributable to benefits in motor function or sleep disturbance. Methods PD patients with unsatisfactory early-morning motor impairment were randomized to optimal-dose (up to 16 mg/24 h) rotigotine or placebo, maintained for 4 weeks. Pain was assessed in the early-morning using an 11-point Likert pain scale (rated average severity of pain (of any type) over the preceding 12 hours from 0 [no pain] to 10 [worst pain ever experienced]). Post hoc analyses for patients reporting ‘any’ pain (pain score ≥1) at baseline, and subgroups reporting ‘mild’ (score 1–3), and ‘moderate-to-severe’ pain (score ≥4) were performed. Likert pain scale change from baseline in rotigotine-treated patients was further analyzed based on a UPDRS III/PDSS-2 responder analysis (a responder defined as showing a ≥30% reduction in early morning UPDRS III total score or PDSS-2 total score). As post hoc analyses, all p values presented are exploratory. Results Of 267 patients with Likert pain data (178 rotigotine, 89 placebo), 187 (70%) reported ‘any’ pain; of these 87 (33%) reported ‘mild’, and 100 (37%) ‘moderate-to-severe’ pain. Change from baseline pain scores decreased with rotigotine compared with placebo in patients with ‘any’ pain (-0.88 [95% CI: -1.56, -0.19], p = 0.013), and in the subgroup with ‘moderate-to-severe’ pain (-1.38 [-2.44, -0.31], p = 0.012). UPDRS III or PDSS-2 responders showed greater improvement in pain than non-responders. Conclusions The results from this post hoc analysis of the RECOVER study suggest that pain was improved in patients with PD treated with rotigotine; this may be partly attributable to benefits in motor function and sleep disturbances. Prospective studies are warranted to investigate this potential benefit and the clinical relevance of these findings.

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Rotigotine transdermal system and evaluation of pain in patients with Parkinson’s disease: a post hoc analysis of the RECOVER study

BMC Neurology Rotigotine transdermal system and evaluation of pain in patients with Parkinson's disease: a post hoc analysis of the RECOVER study Jan Kassubek 0 Kallol Ray Chaudhuri 1 2 Theresa Zesiewicz 6 Erwin Surmann 5 Babak Boroojerdi 4 Kimberly Moran 3 Liesbet Ghys 8 Claudia Trenkwalder 7 0 Department of Neurology, University of Ulm , Oberer Eselsberg 45, 89081 Ulm , Germany 1 MRC Centre for Neurodegeneration Research, King's College , London , UK 2 National Parkinson Foundation Centre of Excellence, King's College Hospital , London , UK 3 UCB Pharma , Smyrna, GA , USA 4 UCB Pharma , Raleigh, NC , USA 5 UCB Pharma , Monheim am Rhein , Germany 6 University of South Florida , Tampa, FL , USA 7 University of Gottingen, Department of Neurosurgery and Paracelsus-Elena Klinik, Center of Parkinsonism and Movement Disorders , Kassel , Germany 8 UCB Pharma , Brussels , Belgium Background: Pain is a troublesome non-motor symptom of Parkinson's disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system. Improvements were also reported on a Likert pain scale (measuring any type of pain). This post hoc analysis of RECOVER further evaluates the effect of rotigotine on pain, and whether improvements in pain may be attributable to benefits in motor function or sleep disturbance. Methods: PD patients with unsatisfactory early-morning motor impairment were randomized to optimal-dose (up to 16 mg/24 h) rotigotine or placebo, maintained for 4 weeks. Pain was assessed in the early-morning using an 11-point Likert pain scale (rated average severity of pain (of any type) over the preceding 12 hours from 0 [no pain] to 10 [worst pain ever experienced]). Post hoc analyses for patients reporting 'any' pain (pain score 1) at baseline, and subgroups reporting 'mild' (score 1-3), and 'moderate-to-severe' pain (score 4) were performed. Likert pain scale change from baseline in rotigotine-treated patients was further analyzed based on a UPDRS III/PDSS-2 responder analysis (a responder defined as showing a 30% reduction in early morning UPDRS III total score or PDSS-2 total score). As post hoc analyses, all p values presented are exploratory. Results: Of 267 patients with Likert pain data (178 rotigotine, 89 placebo), 187 (70%) reported 'any' pain; of these 87 (33%) reported 'mild', and 100 (37%) 'moderate-to-severe' pain. Change from baseline pain scores decreased with rotigotine compared with placebo in patients with 'any' pain (-0.88 [95% CI: -1.56, -0.19], p = 0.013), and in the subgroup with 'moderate-to-severe' pain (-1.38 [-2.44, -0.31], p = 0.012). UPDRS III or PDSS-2 responders showed greater improvement in pain than non-responders. Conclusions: The results from this post hoc analysis of the RECOVER study suggest that pain was improved in patients with PD treated with rotigotine; this may be partly attributable to benefits in motor function and sleep disturbances. Prospective studies are warranted to investigate this potential benefit and the clinical relevance of these findings. Parkinson's disease; Pain; Rotigotine; Dopamine receptor agonist - Background Pain is a common and challenging non-motor symptom of Parkinsons disease (PD), occurring in 40% to 85% of patients with PD [1], with a higher prevalence and intensity than in age-matched non-PD controls [1-5]. Pain is rated by patients as one of the most troublesome symptoms in both early and advanced stages of PD [6], and is associated with reduced health-related quality of life [6-10]. The complexity of PD-associated pain is exemplified by the many different types and distributions of pain, and the poor understanding of the mechanisms of the pain syndrome. The origin of pain in PD may be directly attributable to the patients motor symptoms such as rigidity, dystonia, akinesia, or postural abnormalities. Musculoskeletal pain is the most commonly reported type of pain (by up to 70% of patients [1,2,11]) and may be related to the presence of rigidity and akinesia, as well as comorbid rheumatologic and orthopedic diseases, which can result from pathologic postures such as camptocormia [12]. Pain associated with dystonic symptoms, including spasms, has been reported by up to 40% of PD patients [1,2,11] and is often associated with levodopa wearing off as the disease progresses, particularly in the early morning [13]. In addition to pain being secondary to motor symptoms, data also suggest that altered central pain processing in PD may lead to a decreased pain threshold and abnormal pain-evoked response, resulting in a predisposition to develop pain [11,13,14]. Rotigotine is a dopamine receptor agonist with activity across D1 through D5 receptors as well as select adrenergic and serotonergic sites [15]; continuous transdermal delivery of rotigotine m (...truncated)


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Jan Kassubek, Kallol Chaudhuri, Theresa Zesiewicz, Erwin Surmann, Babak Boroojerdi, Kimberly Moran, Liesbet Ghys, Claudia Trenkwalder. Rotigotine transdermal system and evaluation of pain in patients with Parkinson’s disease: a post hoc analysis of the RECOVER study, BMC Neurology, 2014, pp. 42, 14, DOI: 10.1186/1471-2377-14-42