Dose‐Dependent Effects of AbobotulinumtoxinA (Dysport) on Spasticity and Active Movements in Adults With Upper Limb Spasticity: Secondary Analysis of a Phase 3 Study

O’Dell, Michael W.; Brashear, Allison; Jech, Robert; Lejeune, Thierry; Marqué, P.; Bensmaïl, Djamel; Ayyoub, Ziyad; Simpson, David M.; Volteau, Magali; Vilain, Claire; Picaut, Philippe; Graciès, Jean Michel

doi:10.1016/j.pmrj.2017.06.008

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…It is well known that the amount of active BoNT-A injected is positively correlated to the duration of action (muscle paralysis) of the treatment. This dose–duration relationship has been clearly demonstrated in animal models [28], and a dose–efficacy relationship has been seen in patients with upper limb spasticity, though duration of response was not explored in this study [40]. Other clinical studies from the field of aesthetic medicine, however, have provided evidence for a dose–duration relationship [41,42,43].…”

Section: Discussionmentioning

confidence: 62%

AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients

Field

Splevins

Picaut³

et al. 2018

Toxins

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116

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Botulinum neurotoxin type-A (BoNT-A) blocks the release of acetylcholine from peripheral cholinergic nerve terminals and is an important option for the treatment of disorders characterised by excessive cholinergic neuronal activity. Several BoNT-A products are currently marketed, each with unique manufacturing processes, excipients, formulation, and non-interchangeable potency units. Nevertheless, the effects of all the products are mediated by the 150 kDa BoNT-A neurotoxin. We assessed the quantity and light chain (LC) activity of BoNT-A in three commercial BoNT-A products (Dysport®; Botox®; Xeomin®). We quantified 150 kDa BoNT-A by sandwich ELISA and assessed LC activity by EndoPep assay. In both assays, we assessed the results for the commercial products against recombinant 150 kDa BoNT-A. The mean 150 kDa BoNT-A content per vial measured by ELISA was 2.69 ng/500 U vial Dysport®, 0.90 ng/100 U vial Botox®, and 0.40 ng/100 U vial Xeomin®. To present clinically relevant results, we calculated the 150 kDa BoNT-A/US Food and Drug Administration (FDA)-approved dose in adult upper limb spasticity: 5.38 ng Dysport® (1000 U; 2 × 500 U vials), 3.60 ng Botox® (400 U; 4 × 100 U vials), and 1.61 ng Xeomin® (400 U; 4 × 100 U vials). EndoPep assay showed similar LC activity among BoNT-A products. Thus, greater amounts of active neurotoxin are injected with Dysport®, at FDA-approved doses, than with other products. This fact might explain the long duration of action reported across multiple indications, which benefits patients, caregivers, clinicians, and healthcare systems.

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Section: Discussionmentioning

confidence: 62%

AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients

Field

Splevins

Picaut³

et al. 2018

Toxins

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116

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“…[10][11][12] Full details of patient flow and of patient demographics, baseline characteristics, and mean dose of abobotulinumtoxinA injected into each of the muscle groups can be found in the original study publications. [10][11][12]18 In general, patient demographics and baseline characteristics were similar between studies; across double-blind treatment groups of both studies, the mean age was 51 to 53 years, 62% to 70% of patients were male, and in 83% to 92% of patients, the cause of spastic paresis was stroke. CX A values at baseline of the double-blind study are shown in Table 1.…”

Section: Patientsmentioning

confidence: 88%

Composite active range of motion (CX_A) and relationship with active function in upper and lower limb spastic paresis

Bayle

Maisonobe

Raymond³

et al. 2020

Clin Rehabil

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Objective: The aim of this study is to evaluate a novel composite measure of active range of motion (XA) and determine whether this measure correlates with active function. Design: Post hoc analysis of two randomized, placebo-controlled, double-blind studies with open-label extensions exploring changes in active function with abobotulinumtoxinA. Setting: Tertiary rehabilitation centers in Australia, Europe, and the United States. Subjects: Adults with upper ( n = 254) or lower ( n = 345) limb spastic paresis following stroke or brain trauma. Interventions: AbobotulinumtoxinA (⩽5 treatment cycles) in the upper or lower limb. Main measures: XA was used to calculate a novel composite measure (CXA), defined as the sum of XA against elbow, wrist, and extrinsic finger flexors (upper limb) or soleus and gastrocnemius muscles (lower limb). Active function was assessed by the Modified Frenchay Scale and 10-m comfortable barefoot walking speed in the upper limb and lower limb, respectively. Correlations between CXA and active function at Weeks 4 and 12 of open-label cycles were explored. Results: CXA and active function were moderately correlated in the upper limb ( P < 0.0001–0.0004, r = 0.476–0.636) and weakly correlated in the lower limb ( P < 0.0001–0.0284, r = 0.186–0.285) at Weeks 4 and 12 of each open-label cycle. Changes in CXA and active function were weakly correlated only in the upper limb (Cycle 2 Week 12, P = 0.0160, r = 0.213; Cycle 3 Week 4, P = 0.0031, r = 0.296). Across cycles, CXA improvements peaked at Week 4, while functional improvements peaked at Week 12. Conclusion: CXA is a valid measure for functional impairments in spastic paresis. CXA improvements following abobotulinumtoxinA injection correlated with and preceded active functional improvements.

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“…Four such studies have demonstrated the efficacy of aboBoNTA (Dysport®) in improving clinical outcomes and function across a number of indications; these include adults with upper or lower limb spastic paresis following a stroke or traumatic brain injury ( 15 – 17 ), children with lower limb spastic paresis as a result of cerebral palsy ( 18 , 19 ), and adults with cervical dystonia ( 20 ). These trials established the clinical efficacy of aboBoNTA; a separate dose-ranging analysis in the upper limb reported dose-dependent improvements in spasticity and in active movement with aboBoNTA ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

Duration of Symptom Relief Between Injections for AbobotulinumtoxinA (Dysport®) in Spastic Paresis and Cervical Dystonia: Comparison of Evidence From Clinical Studies

et al. 2020

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Background: Botulinum toxin-A is a well-established treatment for adult and pediatric spastic paresis and cervical dystonia. While guidelines and approved labels indicate that treatment should not occur more frequently than every 12 weeks, studies and real-world evidence show that the timing of symptom recurrence between treatments may vary. Methods: We report retreatment criteria and response duration (retreatment intervals) from four pivotal, double-blind, placebo-controlled studies with open-label extensions involving patients treated with abobotulinumtoxinA (aboBoNTA) for upper limb (NCT01313299) or lower limb (NCT01249404) spastic paresis in adults, lower limb spastic paresis in children (NCT01249417), and cervical dystonia in adults (NCT00257660). We review results in light of recently available preclinical data. Results: In spastic paresis, 24.0-36.9% of upper limb patients treated with aboBoNTA and 20.1-32.0% of lower limb patients did not require retreatment before 16 weeks. Moreover, 72.8-93.8% of aboBoNTA-treated pediatric patients with lower limb spastic paresis did not require retreatment before 16 weeks (17.7-54.0% did not require retreatment before 28 weeks). In aboBoNTA-treated patients with cervical dystonia, 72.6-81.5% did not require retreatment before 16 weeks. Conclusion: AboBoNTA, when dosed as recommended, offers symptom relief beyond 12 weeks to many patients with spastic paresis and cervical dystonia. From recently available preclinical research, the amount of active neurotoxin administered with aboBoNTA might be a factor in explaining this long duration of response.

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Dose‐Dependent Effects of AbobotulinumtoxinA (Dysport) on Spasticity and Active Movements in Adults With Upper Limb Spasticity: Secondary Analysis of a Phase 3 Study

Abstract: I.

Cited by 11 publications

References 28 publications

AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients

AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients

Composite active range of motion (CX_A) and relationship with active function in upper and lower limb spastic paresis

Duration of Symptom Relief Between Injections for AbobotulinumtoxinA (Dysport®) in Spastic Paresis and Cervical Dystonia: Comparison of Evidence From Clinical Studies

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Dose‐Dependent Effects of AbobotulinumtoxinA (Dysport) on Spasticity and Active Movements in Adults With Upper Limb Spasticity: Secondary Analysis of a Phase 3 Study

Abstract: I.

Cited by 11 publications

References 28 publications

AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients

AbobotulinumtoxinA (Dysport®), OnabotulinumtoxinA (Botox®), and IncobotulinumtoxinA (Xeomin®) Neurotoxin Content and Potential Implications for Duration of Response in Patients

Composite active range of motion (CXA) and relationship with active function in upper and lower limb spastic paresis

Duration of Symptom Relief Between Injections for AbobotulinumtoxinA (Dysport®) in Spastic Paresis and Cervical Dystonia: Comparison of Evidence From Clinical Studies

Contact Info

Product

Resources

About

Composite active range of motion (CX_A) and relationship with active function in upper and lower limb spastic paresis