UK-BNO-230019. DOP: January 2023.
BOTOX® has proven evidence and experience in post‑stroke spasticity (PSS) in both the upper and lower limb5-7
BOTOX® has proven efficacy in upper limb PSS6
BOTOX® significantly* reduced finger flexor tone compared to placebo at Week 6 and 126
Adapted from Brashear A, et al 2002.6
*p<0.001 versus placebo.
Study context: A randomised, double-blind, placebo-controlled, multi-centre trial assessed the efficacy and safety of BOTOX® in 126 subjects with increased flexor tone in the wrist and fingers after a stroke. The primary endpoint was Disability Assessment Scale score at Week 6.6
BOTOX® significantly* reduced wrist flexor tone compared to placebo at Week 6 and 126
Adapted from Brashear A, et al 2002.6
*p<0.001 versus placebo.
Study context: A randomised, double-blind, placebo-controlled, multi-centre trial assessed the efficacy and safety of BOTOX® in 126 subjects with increased flexor tone in the wrist and fingers after a stroke. The primary endpoint was Disability Assessment Scale score at Week 6.6
BOTOX®: Up to 46% reduction in wrist flexor tone with repeated treatment8
Adapted from Elovic EP, et al. 20088
Patients reinjected every 12 weeks starting at week 0.
Botulinum toxin type A <250 U: n=66.
All changes from baseline were significant (p<0.01).
Study context: A multi-centre, open-label, repeated-dose study, to assess the safety and evaluate the effects of repeated treatments with BOTOX® on functional disability, quality of life and muscle tone of patients with upper limb post-stroke spasticity, as well as its effect on caregivers.8
BOTOX® has proven efficacy in lower limb PSS9-11
BOTOX® treatment met the primary endpoint as it led to a significant improvement in ankle MAS compared to placebo in the ITT population (p=0.01)9
The post-hoc analysis showed that additional BOTOX® injections to the toe flexors significantly improved both the ankle MAS and CGI scores compared to placebo (p=0.002 and p=0.023 respectively).9
Adapted from Esquenazi A, et al. 20199
Study context: This was a multicentre, randomised, double-blind, placebo-controlled 12 week study of the efficacy and safety of BOTOX® for treating post-stroke lower limb spasticity of the ankle. The primary outcome was the change form baseline in MAS of the ankle, using the averaged score of weeks 4 and 6.9
Significantly* more patients improved their ankle MAS score by ≥1 grade following BOTOX® treatment compared to placebo over 1 year10
The mean change from baseline in ankle MAS (average score of Weeks 4 and 6) was superior for BOTOX® (-0.81 [SD=0.874]) compared with placebo (-0.61 [SD=0.835], p=0.01).10
Sustained benefits of BOTOX® were observed in the subsequent 1-year open-label phase.10
Adapted from Wein T, et al. 201810
*p≤0.04 vs placebo.
Study context: a multicentre, randomised, double-blind, placebo-controlled trial evaluating the efficacy, safety and sustained benefit of BOTOX® in adults with post-stroke lower limb spasticity. Primary endpoint was ankle MAS change from baseline (average score at Weeks 4 and 6).10
BOTOX®: Improvement in ankle muscle tone continued after repeated treatment11
Adapted from Allergan Data on File11
**p <0.001 vs. placebo.
In the placebo-controlled cycle, the patients received either BOTOX® 300 U or placebo. In the open label phase, all the patients received BOTOX® 300 U. Mean baseline of MAS ankle score: BOTOX®: 3.28. Placebo: 3.24.
The primary efficacy endpoint was the area under the curve (AUC) of the change from baseline MAS ankle score during the 12-week double-blind phase.11
Treatment with BOTOX® within 4–6 weeks significantly improved all four measures of gait analysis at Week 8 compared to placebo12
Adapted from Tao W, et al. 201512
There was no clinically meaningful improvement in function as measured by the PRS and speed of gait. BOTOX® should only be used for the treatment of focal spasticity in adult post-stroke patients if muscle tone reduction is expected to result in improved function (e.g. improvements in gait), or improved symptoms (e.g. reduction in muscle spasms or pain), and/or to facilitate care.5
This low-powered study provides limited initial evidence that treating post-stroke spasticity early on with BOTOX® may lead to positive results for patients. †p<0.05.
Please refer to the BOTOX® SmPC for further information relating to dosing and administration. The recommended dose for focal lower limb spasticity associated with stroke is 300 Units to 400 Units (maximum), divided among up to 6 muscles as follows. Gastrocnemius medial head: 75 Units, 3 sites; Gastrocnemius lateral head: 75 Units, 3 sites; Soleus: 75 Units, 3 sites; Tibialis posterior: 75 Units, 3 sites; Flexor hallucis longus: 50 Units, 2 sites; Flexor digitorum longus: 50 Units, 2 sites; Flexor digitorum brevis: 25 Units, 1 site.5
BOTOX® helps patients benefit from pain reduction13-15
Upper limb pain14 (week 6 after each treatment vs. baseline)
BOTOX®: sustained reduction in mean score of the pain domain of the Disability Assessment Scale across 4 treatment cycles (n=110, 94, 77, 25) vs. baseline14
BOTOX®: 25–33% of patients benefitted from reduction in disability caused by pain (n=111)14
Study context: Evaluation of the long-term efficacy and safety of BOTOX® in post-stroke spasticity patients who completed a 12-week placebo-controlled study and received multiple open-label treatments with BOTOX® for 42 weeks. The 4-point Disability Assessment Scale was used to assess four domains, of which pain was one.14
Lower limb pain15 (week 10 vs. baseline)
Significantly more patients had a ≥50% reduction in pain score during passive stretch at week 10, post second injection, with BOTOX® than with placebo (p=0.039)15
Study context: The BOTOX® Economic Spasticity Trial (BEST) was a multi centre, randomised, double-blind, placebo-controlled trial - aimed at comparing the effectiveness of BOTOX® plus standard care, versus placebo plus standard care, on pain. Pain intensity in response to limb stretch was assessed on an 11-point numeric rating scale ranging from 0 (no pain) to 10 (pain as bad as it can be imagined).15
BOTOX® helps significantly more patients achieve both upper and lower limb functional goals compared to placebo6,16
UPPER LIMB
...of wrist and finger spasticity patients reported improvements toward their functional goals at week 6 (n=64, p<0.001 versus placebo)6
LOWER LIMB
...of lower limb spasticity patients reported treatment benefits at week 16 (n=28, p≤0.05 versus placebo)16
BoNTA, botulinum toxin type A; CGI: Clinical Global Impression of Change; FDL: flexor digitorum brevis; FHL: flexor hallucis longus; ITT: intention-to-treat; MAS: Modified Ashworth Scale; PRS: Physician’s Rating Scale; PSS: post-stroke spasticity; SD: standard deviation; QoL: quality of life; U: units.
BOTOX® (botulinum toxin type A) is indicated for the treatment of focal spasticity including:5
- wrist and hand disability due to upper limb spasticity associated with stroke in adults
- ankle and foot disability due to lower limb spasticity associated with stroke in adults
References
- Allergan. Data on file. INT/0423/2016(1). 2018.
- Aurora S K, Winner P et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache 2011;51(9):1358-1373
- Blumenfeld A M, Stark R J et al. Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study. J Headache Pain 2018;19(1):13
- Allergan. Data on file. 014
- BOTOX® Summary of Product Characteristics. Available at: www.medicines.org.uk. Accessed November 2022
- Brashear A, Gordon MF et al. Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke. NEJM 2002;347:395-400
- Kaji R, Osako Y et al. Botulinum toxin type A in post-stroke lower limb spasticity: a multicenter, double-blind, placebo-controlled trial. J Neurol. 2010;257(8):1330-7
- Elovic EP, Brashear A et al. Repeated treatments with botulinum toxin type a produce sustained decreases in the limitations associated with focal upper-limb poststroke spasticity for caregivers and patients. Archives of physical medicine and rehabilitation 2008;89: 799-806
- Esquenazi A, Wein TH et al. Optimal muscle selection for onabotulinumtoxina injections in poststroke lower-limb spasticity: a randomized trial. Am J Phys Med Rehabil. 2019;98:360-368
- Wein T, Esquenazi A et al. OnabotulinumtoxinA for the treatment of poststroke distal lower limb spasticity: a randomized trial. PM&R. 2018;10(7):693-703
- Allergan, Data on file. 023: BOTOX
- Tao W, Yan D et al. Gait improvement by low-dose botulinum toxin A injection treatment of the lower limbs in subacute stroke patients. J Phys Ther Sci. 2015;27:759-762
- Ward AB, Wissel J et al. Functional goal achievement in post-stroke spasticity patients: the BOTOX® Economic Spasticity Trial (BEST). J Rehabil Med. 2014;46:504-513
- Gordon MF, Brashear A et al. Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke. Neurology. 2004;63(10):1971-3
- MHRA. BOTOX® 50 Allergan Units Powder for Solution for Injection. PL 00426/0018 UKPAR
- Allergan. Data on file. BOTOX 0684. November 2018
- Allergan. Data on file. BOTOX 0680. November 2018
Please refer to the BOTOX® Summary of Product Characteristics for further information on adverse events, contraindications and special warnings and precautions for use.
Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or via the MHRA Yellow Card app, available in the Google Play or Apple App Stores.
Adverse events should also be reported to AbbVie on [email protected]
Date of preparation: November 2022. UK-BTX-220208.
