Efficacy and safety of incobotulinumtoxinA in post-stroke upper-limb spasticity in Japanese subjects: results from a randomized, double-blind, placebo-controlled study (J-PURE)

Abstract

Background Upper-limb spasticity frequently occurs after stroke and there is a clinical need for more effective therapies. The Phase III J-PURE study assessed the efficacy and safety of incobotulinumtoxinA up to 400 U for post-stroke upper-limb spasticity in Japan. Methods In the 12-week main period (MP) of this double-blind, placebo-controlled study, Japanese subjects with upperlimb spasticity received one injection cycle of incobotulinumtoxinA 400 U, 250 U, or matching placebo. Eligible subjects enrolled in an open-label extension (OLEX) period of three injection cycles of incobotulinumtoxinA 400 U (32-40 weeks). The primary objective was to establish the efficacy of a single incobotulinumtoxinA injection using the Modified Ashworth Scale (MAS) wrist score. Secondary efficacy outcomes and safety were also assessed. Results Among 100 treated subjects, AUCs for incobotulinumtoxinA 400 and 250 U were significantly different versus placebo (p = 0.0014 and p = 0.0031, respectively) for change from baseline in MAS wrist score to the end of the MP, with similar results from baseline to week 4. IncobotulinumtoxinA 400 U was superior versus placebo across other spasticity patterns and at most study visits. Improvements were maintained throughout the OLEX period. Disability Assessment Scale and Investigator's Clinical Global Impression scores improved significantly for incobotulinumtoxinA 400 U versus placebo from baseline to week 4 (p = 0.0067 and p < 0.0001, respectively). IncobotulinumtoxinA was well tolerated up to 52 weeks, with no unexpected adverse events. Conclusion IncobotulinumtoxinA reduced (pathologically) increased muscle tone, improved functionality and was well tolerated in Japanese subjects with post-stroke upper-limb spasticity.

Pain Reduction in Adults with Limb Spasticity Following Treatment with IncobotulinumtoxinA: A Pooled Analysis

“…This pooled analysis of six studies, four of which were randomised, double-blind and placebo-controlled in design, showed that incobotulinumtoxinA significantly reduces pain compared with placebo in adult patients with upper limb spasticity-associated pain. These results confirm the pain-relieving benefits of incobotulinumtoxinA observed in the individual studies [12,14,15,27,34]. In this pooled population of patients with limb spasticity considered suitable for treatment with BoNT-A, approximately 60% of patients experienced pain at baseline.…”

“…Analyses were based on pooled results from six prospective, multicentre, Phase 2 or 3 studies of incobotulinumtoxinA (Xeomin ® ; Merz Pharmaceuticals GmbH, Frankfurt, Germany) in the treatment of upper (five studies: MRZ_60201_0307); [12,14,27,34]) and/or lower (one study: [15]) limb muscle spasticity in adults. The studies were part of the clinical development programme for incobotulinumtoxinA and were performed across multiple countries and continents worldwide, including Europe, Canada, USA, Japan, India and Russia.…”

“…The prevalence of pain among patients with limb spasticity varies widely from 46% to 74% depending on the patient population studied [19][20][21]. The efficacy of BoNT-A in reducing pain in patients with upper and lower limb spasticity has been investigated in clinical studies, either as a primary outcome [20][21][22][23][24][25] or a secondary outcome [12,14,15,17,[26][27][28][29][30][31][32][33][34][35]. These studies have involved cohorts with sizes varying from 11 patients [29] to 487 patients [23].…”

Can Incobotulinumtoxin-A Treatment Improve Quality of Life Better Than Conventional Therapy in Spastic Muscle Post-Stroke Patients? Results from a Pilot Study from a Single Center

“…The 12-week, double-blind, placebo-controlled study shows that active movement improves in the study group that received treatment with botulinum toxin type A. Furthermore, the scale of disability and clinical evaluation according to the examiner′s overall impression show that INCO reduced increased muscle tone, improved functionality, and was well tolerated in Japanese subjects with upper limb spasticity after stroke [ 27 ].…”

Clinical Uses of a Robot (Hybrid-Assisted Limb or HAL™) in Patients with Post-stroke Spasticity after Botulinum Toxin Injections

“…Botulinum neurotoxins (BoNTs) have been approved for spasticity treatment in many countries. There is strong evidence that they reduce muscle tone in spasticity (5,6), but it is uncertain whether they are useful in improving functional disabilities of the limbs such as increasing active range of motion (ROM). Spasticity is defined as increased muscle tone as a consequence of upper motor neuron dysfunction or loss.…”