OnabotulinumtoxinA for Lower-Limb Spasticity: Guidance from a Delphi Panel Approach (original) (raw)
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PM & R : the journal of injury, function, and rehabilitation, 2016
OnabotulinumtoxinA reduces muscle hypertonia associated with post-stroke spasticity (PSS). PSS manifests as several common postures. To define treatment paradigms for PSS upper-limb common postures. Modified Delphi method. Expert panel. Ten injectors experienced in the treatment and clinical research of PSS (physiatrists and neurologists) were invited to participate in the Delphi panel. The Delphi panel reviewed an electronic worksheet with PSS upper limb postures to define onabotulinumtoxinA treatment paradigms (Round 1). During Round 2, panel members discussed in person Round 1 results and voted until consensus (≥66% agreement). Recommendations were geared toward those with new or early injection experience. Expert consensus on onabotulinumtoxinA treatment parameters for PSS including muscles to inject, dose per muscle and posture, and treatment adjustments for suboptimal response. For each posture, consensus was reached on targeted subsets of muscles. Doses ranged for individual ...
Journal of Neural Transmission
The aim of this study in patients with post-stroke lower limb spasticity (PSLLS) was to evaluate the relationship between time of onabotulinumtoxinA treatment relative to stroke and efficacy outcomes. This was a phase 3, international, multicenter, randomized, 12-week, double-blind study, followed by a repeated treatment, open-label extension. Patients were aged 18–85 years with PSLLS (Modified Ashworth Scale [MAS] ≥ 3) of the ankle with the most recent stroke occurring ≥ 3 months before screening. Patients (double-blind phase) were randomized (n = 468) to onabotulinumtoxinA 300–400 U (300 U, mandatory ankle muscles (gastrocnemius, soleus, tibialis posterior); and ≤ 100 U, optional lower limb muscles (flexor digitorum longus, flexor hallucis longus, flexor digitorum brevis, extensor hallucis, and rectus femoris]) or placebo. Primary endpoint: MAS change from baseline (average score of weeks 4 and 6). Secondary endpoints: physician-assessed Clinical Global Impression of Change (CGI) ...
PM&R
Introduction: OnabotulinumtoxinA treatment for spasticity is dependent on numerous factors and varies according to selected treatment goals. Objective: To examine real-world onabotulinumtoxinA treatment utilization and effectiveness in patients with upper limb spasticity over 2 years from the Adult Spasticity International Registry (ASPIRE) study. Design: Multicenter, prospective, observational registry (NCT01930786). Setting: Fifty-four international clinical sites in North America, Europe, and Asia. Patients: Adults (naïve or non-naïve to botulinum toxins for spasticity) with upper limb focal spasticity related to upper motor neuron syndrome across multiple etiologies. Interventions: OnabotulinumtoxinA administered at clinician's discretion. Main Outcome Measures: OnabotulinumtoxinA utilization, clinician and patient satisfaction. Results: Four hundred eighty-four patients received ≥1 treatment of onabotulinumtoxinA for upper limb spasticity. Patients were on average 55.1 years old, 50.8% male, predominantly Caucasian (72.3%), and 38.6% were naïve to botulinum toxins. Stroke was the most frequently reported underlying etiology (74.0%). Most patients (81.2%) had moderate to severe spasticity at baseline. The most commonly treated upper limb clinical presentation was clenched fist (79.1% of patients). Across all presentations, onabotulinumtoxinA doses ranged between 5-600U. Electromyography (EMG) was most often utilized to localize muscles (≥57.0% of treatment sessions). Clinicians (92.9% of treatment sessions) and patients (85.7%) reported being extremely satisfied/satisfied that treatment helped manage spasticity, and clinicians (98.6%) and patients (92.2%) would definitely/probably continue onabotulinumtoxinA treatment. One hundred seventy-nine patients (37.0%) reported 563 adverse events (AEs); 15 AEs in 14 patients (2.9%) were considered treatment related. Sixty-nine patients (14.3%) reported 137 serious AEs; 3 serious AEs in 2 patients (0.4%) were considered treatment related. No new safety signals were identified. Conclusions: ASPIRE captured the real-world individualized nature of onabotulinumtoxinA utilization for upper limb spasticity over 2 years, with consistently high clinician-and patient-reported satisfaction. Data in this primary analysis will guide clinical use of onabotulinumtoxinA, as well as provide insights to improve educational programs on spasticity management.
Toxins
Background: OnabotulinumtoxinA (BoNT-A) can temporarily decrease spasticity following stroke, but whether there is an associated improvement in upper limb function is less clear. This study measured the benefit of adding weekly rehabilitation to a background of BoNT-A treatments for chronic upper limb spasticity following stroke. Methods: This was a multi-center clinical trial. Thirty-one patients with post-stroke upper limb spasticity were treated with BoNT-A. They were then randomly assigned to 24 weeks of weekly upper limb rehabilitation or no rehabilitation. They were injected up to two times, and followed for 24 weeks. The primary outcome was change in the Fugl-Meyer upper extremity score, which measures motor function, sensation, range of motion, coordination, and speed. Results: The 'rehab' group significantly improved on the Fugl-Meyer upper extremity score (Visit 1 = 60, Visit 5 = 67) while the 'no rehab' group did not improve (Visit 1 = 59, Visit 5 = 59; p = 0.006). This improvement was largely driven by the upper extremity "movement" subscale, which showed that the 'rehab' group was improving (Visit 1 = 33, Visit 5 = 37) while the 'no rehab' group remained virtually unchanged (Visit 1 = 34, Visit 5 = 33; p = 0.034). Conclusions: Following injection of BoNT-A, adding a program of rehabilitation improved motor recovery compared to an injected group with no rehabilitation.
High doses of onabotulinumtoxinA in post-stroke spasticity: a retrospective analysis
Journal of neural transmission (Vienna, Austria : 1996), 2015
We retrospectively evaluated the efficacy and safety of high doses of onabotulinumtoxinA (from 600 to 800 units) in 26 patients affected by upper and/or lower limb post-stroke spasticity. They were assessed before, 30 and 90 days after treatment. We observed a significant muscle tone reduction and a significant functional improvement (assessed with the Disability Assessment Scale). No adverse events were reported. In our retrospective analysis the treatment with high doses of onabotulinumtoxinA showed to be effective and safe.
Dose response with onabotulinumtoxinA for post-stroke spasticity: A pooled data analysis
Movement Disorders, 2010
Clinical trials demonstrate that ona-botulinumtoxinA reduces upper limb post-stroke spasticity, with therapeutic response influenced by injected dose. Individual studies provide limited insight regarding muscle group-specific dose-response relationships. Our objective was to characterize dose-response relationships between onabotulinumtoxinA and muscle tone in specific upper limb muscles. Individual patient data from seven multicenter, randomized, double-blind, placebo-controlled trials were pooled. Of 544 post-stroke patients enrolled, 362 received onabotulinumtoxinA and 182 received placebo, injected into the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), flexor digitorum profundus (FDP), and/or biceps brachii (BB). Ashworth Scale score change at week 6 (AshworthCBL) was the primary outcome measure for muscle tone. For a broader analysis of response, AshworthCBL/onabotulinumtoxinA dosage relationships were characterized using three techniques: (1) AshworthCBL plotted as a function of onabotulinum-toxinA dose in Units (U) [dose-response curve]; (2) mean AshworthCBL per onabotulinumtoxinA dose depicting the responses seen with specific dose injection clusters/groups for each specific muscle group; and (3) onabotulinumtoxinA dose estimated to produce a mean 1-point decrease in AshworthCBL as an indicator of clinically meaningful benefit of treatment. Increasing onabotulinumtoxinA doses produced greater AshworthCBLs (muscle tone improvements). The maximal week 6 response (E max) model indicated a saturating dose-response relationship, with mean E max AshworthCBL values of-1.48,-1.48,-0.63,-0.77, and-0.61 in the FCR, FCU, FDS, FDP, and BB, respectively. OnabotulinumtoxinA doses estimated to produce a mean 1-point decrease in AshworthCBL were: 22.5U, 18.4U, 66.3U, 42.5U in the FCR, FCU, FDS, and FDP, respectively, and not determinable in the BB. These analyses demonstrate a saturating effect of greater muscle tone improvements with increasing onabotuli-numtoxinA doses in post-stroke spasticity patients. These findings suggest potentially effective onabotuli-numtoxinA doses in selected muscle groups in this study population. V
Contemporary clinical trials communications, 2017
Introduction: Approximately 15 million people suffer a stroke annually, up to 40% of which may develop spasticity, which can result in impaired limb function, pain and associated involuntary movements affecting motor control. Robust clinical data on spasticity progression, associated symptoms development and functional impairment is scarce. Additionally, maximal duration of muscle tone reduction following botulinum toxin type A (BoNT-A) injections remains undetermined. The ONTIME pilot study aims to explore these issues and evaluate whether abobotulinumtoxinA 500 U (Dysport ® ; Ipsen) administered intramuscularly within 12 weeks following stroke delays the appearance or progression of symptomatic (disabling) upper limb spasticity (ULS). Methods: ONTIME is a 28-week, phase 4, randomised, double-blind, placebo-controlled, exploratory pilot study initiated at four centres across Malaysia, the Philippines, Singapore and Thailand. Subjects (n ¼ 42) with moderate to severe ULS (modified Ashworth scale [MAS] score 2) in elbow flexors or pronators, wrist flexors, or finger flexors will be recruited. Subjects will be randomised 2:1 to abobo-tulinumtoxinA 500 U or placebo (single dose 2e12 weeks after first-ever stroke). Primary efficacy will be measured by time between initial injection and visit at which reinjection criteria (MAS score 2 in the primary targeted muscle group and appearance or reappearance of symptomatic ULS) are met. Follow-up visits will be 4-weekly to a maximum of 28 weeks. Discussion: This pilot study will facilitate the design and sample size calculation of further confirmatory studies, and is expected to provide insights into the optimal management of post-stroke patients, including timing of BoNT-A therapy and follow-up duration.
Journal of pain and symptom management, 2016
Patients with post-stroke spasticity (PSS) commonly experience pain in affected limbs, which may impact quality of life. To assess onabotulinumtoxinA for pain in patients with PSS from the BOTOX(®) Economic Spasticity Trial, a multicenter, randomized, double-blind, placebo-controlled trial. Patients with PSS (N=273) were randomized to 22- to 34-weeks double-blind treatment with onabotulinumtoxinA + standard care (SC) or placebo injection + SC and were eligible to receive open-label onabotulinumtoxinA up to 52 weeks. Assessments included change from baseline on the 11-point pain numeric rating scale, proportion of patients with baseline pain ≥4 achieving ≥30% and ≥50% improvement in pain, and pain interference with work at week 12, end of double-blind treatment, and week 52. At baseline, most patients (74.3%) experienced pain and 47.4% had pain ≥4 (pain subgroup). Mean pain reduction from baseline at week 12 was significantly greater with onabotulinumtoxinA + SC (-0.77, 95% CI -1.14 ...
Journal of the neurological sciences, 2017
Current guidelines suggested a dosage up to 600units (U) of botulinum toxin type A (BoNT-A) (onabotulinumtoxinA or incobotulinumtoxinA) in reducing spastic hypertonia with low prevalence of complications, although a growing body of evidence showed efficacy with the use of high doses (>800U). The available evidence mainly referred to a single set of injections evaluating the efficacy and safety of the neurotoxin 30days after the treatment. In a prospective, non-randomized, open-label study, we studied the safety of repeated higher doses of incobotulinumtoxinA in post-stroke upper and lower limb spasticity. Two years after the first set of injections, we evaluated in 20 stroke survivors with upper and lower limb spasticity the long-term safety of repeated high doses of incobotulinumtoxinA (up to 840U) for a total of eight sets of injections. Patients reported an improvement of their clinical picture concerning a reduction of spasticity measured with the Asworth Scale (AS) for elbow...