Long-term safety of repeated high doses of incobotulinumtoxinA injections for the treatment of upper and lower limb spasticity after stroke

Santamato, Andrea; Intiso, Domenico; Baricich, Alessio; Picelli, Alessandro; Smania, Nicola; Fortunato, Francesca; Seripa, Davide; Fiore, Pietro; Ranieri, Maurizio

doi:10.1016/j.jns.2017.04.052

Cited by 23 publications

(28 citation statements)

References 17 publications

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“…The safety profile observed during the OLEX was similar to the study MP, with no new or unexpected AEs. Repeated incobotulinumtoxinA injections were well tolerated overall, consistent with previous studies of botulinum neurotoxin type A formulations in the treatment of post-stroke spasticity [ 14 , 16 , 22 – 25 ], including a study investigating the long-term safety of repeated high doses of incobotulinumtoxinA over 2 years [ 26 ].…”

Section: Discussionsupporting

confidence: 79%

IncobotulinumtoxinA Efficacy and Safety in Adults with Upper-Limb Spasticity Following Stroke: Results from the Open-Label Extension Period of a Phase 3 Study

et al. 2018

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IntroductionThe objective of the study was to investigate the efficacy and safety of repeated incobotulinumtoxinA injections for the treatment of upper-limb post-stroke spasticity in adults.MethodsAdults 18–80 years of age with post-stroke upper-limb spasticity who completed the 12-week randomized, double-blind, placebo-controlled main period (MP) of a phase 3 trial (NCT01392300) were eligible to enrol in the 36-week open-label extension period (OLEX). The OLEX included three treatment cycles at fixed 12-week injection intervals; subjects were injected with 400 U incobotulinumtoxinA into the affected upper limb. Efficacy assessments included evaluation of muscle tone using the Ashworth Scale (AS) and the Global Impression of Change Scale (GICS) assessed by the investigator, subject, and caregiver. The incidence of adverse events (AEs) was monitored throughout the OLEX.ResultsA total of 296 of 299 subjects (99.0%) who completed the MP received incobotulinumtoxinA in the OLEX, and 248 subjects completed the 36-week OLEX. The proportion of subjects with at least a 1-point improvement in AS score from each incobotulinumtoxinA treatment to the respective 4-week post-injection visit ranged by cycle from 52.3% to 59.2% for wrist flexors, 49.1% to 52.3% for elbow flexors, 59.8% to 64.5% for finger flexors, 35.5% to 41.2% for thumb flexors, and 37.4% to 39.9% for forearm pronators (P < 0.0001 for all). Over 90% of subjects were assessed by the investigator to be at least minimally improved (4 weeks post-injection) on the GICS during each injection cycle; 61.0% in the 1st cycle, 58.2% in the 2nd cycle, and 57.4% in the 3rd cycle were considered much improved or very much improved on the GICS. Three percent of subjects (9/296) reported treatment-related AEs; the most frequently reported were pain in the extremity (n = 2, 0.7%) and constipation (n = 2, 0.7%). Serious AEs were reported by 22 subjects (7.4%); however, none were considered treatment-related.ConclusionsRepeated injections of incobotulinumtoxinA for the treatment of post-stroke upper-limb spasticity led to significant improvements in muscle tone and investigator’s global impression of change. Treatment was well tolerated, with no serious treatment-related AEs.FundingMerz Pharmaceuticals GmbH.

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Section: Discussionsupporting

confidence: 79%

IncobotulinumtoxinA Efficacy and Safety in Adults with Upper-Limb Spasticity Following Stroke: Results from the Open-Label Extension Period of a Phase 3 Study

et al. 2018

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“…In both the onabotulinumtoxinA/onabotulinumtoxinA and the placebo/onabotulinumtoxinA groups, improvements in muscle tone and global clinical response were observed in all repeat cycles, and the magnitude of the improvement generally increased with repeated treatments of onabotulinumtoxinA. This incremental benefit with each [19,20].…”

Section: Discussionmentioning

confidence: 90%

“…Furthermore, the second phase of the trial was open-label and nonblinded. Whereas this is a well-accepted design for assessing efficacy of repeat treatment and long-term safety in clinical trials [19,29], this approach may be subject to potential bias because of the lack of blinding of the open-label phase. The lack of significance in pain outcomes in this study is noteworthy because of its contrast with previous spasticity studies (eg, Botox Economic Spasticity Trial [BEST, NCT00549783]) showing a decrease in pain in individuals injected with onabotulinumtox-inA [30].…”

Section: Discussionmentioning

confidence: 99%

OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity: A Randomized Trial

Wein

Esquenazi

Jost

et al. 2018

PM&R

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“…Some previous studies evaluated the histologic changes of lacrimal gland after BTA injection in the lacrimal gland of rabbits, and showed that BTA injections were not associated with inflammation or structural changes of acini or ductules such as atrophy and fibrosis [9,15]. BTA is also widely used for treating limb spasticity, and previous studies demonstrated a consistent efficacy and safety of repeated BTA injections in patients with upper and lower limb spasticity [16,17]. Taken together, these findings suggest that BTA can be injected in the lacrimal gland repeatedly at the same dosage if needed, and each injection may have a similar efficacy for treating epiphora.…”

Section: Discussionmentioning

confidence: 99%

Repeated injections of botulinum toxin-A for epiphora in lacrimal drainage disorders: qualitative and quantitative assessment

Ahn

Kang

2019

Eye

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Purpose To report the outcome of repeated botulinum toxin-A (BTA) injections in the lacrimal glands in patients with epiphora. Methods We performed retrospective chart review of patients who were injected with 2.5 units of BTA in the lacrimal gland. Epiphora and tear production were assessed by the Munk score and Schirmer-1 test, respectively, pre-injection and at 1 and 3 months post injection. Regarding repeated injections, the effects of the first were compared to those of the second and third injections. Results Forty-six eyes of 35 patients had an average of 2.3 injections per eye (range, 1-6). The mean Munk score significantly decreased from 3.72 to 1.87 at 1 month (p < 0.001) and 2.21 at 3 months (p < 0.001) after injection. The mean Schirmer-1 score also significantly decreased from 15.35 mm to 10.52 mm at 1 month (p < 0.001) and 12.48 mm at 3 months (p < 0.001) after injection. The mean reduction rates of Munk and Schirmer-1 scores after the second (66.1% and 29.8%, respectively) and the third injections (56.1% and 23.3%, respectively) were not significantly different from those after the first injection (63.3% and 26.1%, respectively) (p > 0.05 for each comparison). There was a significant correlation between the difficulty in exposing the lacrimal gland for injection and the risk of complication (p = 0.017). Conclusion BTA injection in the lacrimal gland showed favourable outcomes; repeated injections did not compromise efficacy. BTA injection can be safely repeated for epiphora, especially in patients whose lacrimal gland can be easily exposed.

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Long-term safety of repeated high doses of incobotulinumtoxinA injections for the treatment of upper and lower limb spasticity after stroke

Cited by 23 publications

References 17 publications

IncobotulinumtoxinA Efficacy and Safety in Adults with Upper-Limb Spasticity Following Stroke: Results from the Open-Label Extension Period of a Phase 3 Study

IncobotulinumtoxinA Efficacy and Safety in Adults with Upper-Limb Spasticity Following Stroke: Results from the Open-Label Extension Period of a Phase 3 Study

OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity: A Randomized Trial

Repeated injections of botulinum toxin-A for epiphora in lacrimal drainage disorders: qualitative and quantitative assessment

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