Efficacy and safety of abobotulinumtoxinA in spastic lower limb

Abstract

Objective:To demonstrate single abobotulinumtoxinA injection efficacy in lower limb vs placebo for adults with chronic hemiparesis and assess long-term safety and efficacy of repeated injections.Methods:In a multicenter, double-blind, randomized, placebo-controlled, single-cycle study followed by a 1-year open-label, multiple-cycle extension, adults ≥6 months after stroke/brain injury received one lower limb injection (abobotulinumtoxinA 1,000 U, abobotulinumtoxinA 1,500 U, placebo) followed by ≤4 open-label cycles (1,000, 1,500 U) at ≥12-week intervals. Efficacy measures included Modified Ashworth Scale (MAS) in gastrocnemius–soleus complex (GSC; double-blind primary endpoint), physician global assessment (PGA), and comfortable barefoot walking speed. Safety was the open-label primary endpoint.Results:After a single injection, mean (95% confidence interval) MAS GSC changes from baseline at week 4 (double-blind, n = 381) were as follows: −0.5 (−0.7 to −0.4) (placebo, n = 128), −0.6 (−0.8 to −0.5) (abobotulinumtoxinA 1,000 U, n = 125; p = 0.28 vs placebo), and −0.8 (−0.9 to −0.7) (abobotulinumtoxinA 1,500 U, n = 128; p = 0.009 vs placebo). Mean week 4 PGA scores were as follows: 0.7 (0.5, 0.9) (placebo), 0.9 (0.7, 1.1) (1,000 U; p = 0.067 vs placebo), and 0.9 (0.7, 1.1) (1,500 U; p = 0.067); walking speed was not significantly improved vs placebo. At cycle 4, week 4 (open-label), mean MAS GSC change reached −1.0. Incremental improvements in PGA and walking speed occurred across open-label cycles; by cycle 4, week 4, mean PGA was 1.9, and walking speed increased +25.3% (17.5, 33.2), with 16% of participants walking >0.8 m/s (associated with community mobility; 0% at baseline). Tolerability was good and consistent with the known abobotulinumtoxinA safety profile.Conclusions:In chronic hemiparesis, single abobotulinumtoxinA (Dysport Ipsen) administration reduced muscle tone. Repeated administration over a year was well-tolerated and improved walking speed and likelihood of achieving community ambulation.Clinicaltrial.gov identifiers:NCT01249404, NCT01251367.Classification of evidence:The double-blind phase of this study provides Class I evidence that for adults with chronic spastic hemiparesis, a single abobotulinumtoxinA injection reduces lower extremity muscle tone.

Effects on walking of simultaneous upper/lower limb abobotulinumtoxina injections in patients with stroke or brain injury with spastic hemiparesis

“…AbobotulinumtoxinA (Dysport®, aboBoNT-A) has proven efficacious in the treatment of both LL and UL spasticity when injected separately (8,9). Repeated aboBoNT-A injections into the LL or UL have been associated with improvement in both active movement and function, with increased walking speed observed following repeated LL injections (10,11).…”

“…We report here the results of a post hoc analysis of data from a phase 3 study of aboBoNT-A (11). The objective of this analysis was to evaluate walking speed in patients with spastic hemiparesis who received abo-BoNTA, comparing outcomes in those patients treated solely in the LL with those receiving simultaneous treatment in both the LL and UL.…”

“…The phase 3, open-label (OL) extension study of aboBoNT-A (NCT01251367) followed a double-blind (DB) study (NCT01249404), as described previously (11). Briefly, the DB phase was a multicentre, prospective, randomized, placebocontrolled study in adults with chronic hemiparesis who received a single injection of 1,000 U or 1,500 U aboBoNT-A or placebo into both soleus and gastrocnemius muscles and ≥ 1 other (investigator-selected) LL muscle(s).…”

Botulinum toxin for spasticity: a case for change to the Pharmaceutical Benefits Scheme

“…For cerebral palsy, only adults who were treated as children can receive botulinum toxin, in spite of the fact that current research and clinical experience suggest that adult patients with cerebral palsy respond well to the toxin 12 . For instances of stroke, while upper limb spasticity post‐stroke can be treated (minimally), post‐stroke lower limb spasticity and foot dystonia are excluded, although the reduction of both is critical to walking 13 …”

“…12 For instances of stroke, while upper limb spasticity post-stroke can be treated (minimally), post-stroke lower limb spasticity and foot dystonia are excluded, although the reduction of both is critical to walking. 13 Unfortunately, the PBS guidelines reflect outdated information about the treatment of spasticity in either the upper or lower limbs following stroke (and other neurological disorders). Several methodological flaws such as inappropriate patient selection, injection protocols and study designs were reported with botulinum toxin trials.…”