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

Jan Kassubek, Kallol Ray Chaudhuri, Theresa Zesiewicz, Erwin Surmann, Babak Boroojerdi, Kimberly Moran, Liesbet Ghys, Claudia Trenkwalder, Jan Kassubek, Kallol Ray Chaudhuri, Theresa Zesiewicz, Erwin Surmann, Babak Boroojerdi, Kimberly Moran, Liesbet Ghys, Claudia Trenkwalder

Abstract

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.

Figures

Figure 1
Figure 1
Likert pain scale change from baseline in patients with pain at baseline.†ANCOVA model with treatment and region as factors and baseline pain score as the covariate. ANCOVA: analysis of covariance; CI: confidence interval; LS: least square; SD: standard deviation.
Figure 2
Figure 2
Likert pain scale change from baseline in rotigotine-treated patients by A. UPDRS III responder status, and B. PDSS-2 responder status.†ANCOVA model with UPDRS III/PDSS-2 responder status and region as factors and baseline pain score as the covariate. ANCOVA: analysis of covariance; CI: confidence interval; LS: least square; PDSS-2: Parkinson’s Disease Sleep Scale; SD: standard deviation; UPDRS III: Unified Parkinson’s Disease Rating Scale.

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