Effect of early use of abobotulinumtoxinA (DYSPORT®) after stroke on spasticity progression: First results of a pilot study

Abstract

Objective To determine whether early post-stroke (within 12 weeks) abobotulinumtoxinA (aboBoNT-A; Dysport ® ) injections delay the appearance or progression of upper limb symptomatic spasticity. Prevalence and severity of spasticity continues to increase during the first year after stroke. However, muscle tone changes in the affected limb may be apparent within 2 weeks of stroke. AboBoNT-A is a recognized effective focal intervention for reducing upper limb spasticity, but is usually administered ≥ 3 months post-stroke. There are limited data regarding whether early treatment with botulinum toxin A delays development of symptomatic post-stroke spasticity. Material/Patients and methods The ONTIME pilot study was a 28-week, phase IV, randomized (2:1, aboBoNT-A 500U:placebo), double-blind study to assess the impact of aboBoNT-A intramuscular injections administered within 2–12 weeks post-stroke on appearance or reappearance of symptomatic spasticity in patients with Modified Ashworth Scale (MAS; muscle tone) score ≥ 2 at baseline. Primary endpoint was time between first injection and visit when composite reinjection criteria were met. Reinjection criterion was a novel composite index, defined as a MAS score ≥ 2 and one of the following signs of symptomatic (disabling) spasticity: pain, involuntary movements, impaired active or passive function. Results Forty-two patients (28 aboBoNT-A, 14 placebo; 78.6% male; mean [SD] age, 59.8 [12.3] years; MAS ≥ 2) from Malaysia, Philippines, Singapore and Thailand were randomized and injected; 76.2% had symptomatic spasticity and median [range] time since stroke was 5.86 [2.3–11.7] weeks. In most patients (73.8%), elbow flexors were selected as the primary target muscle group. Median [95% CI] time to reaching reinjection criteria was 156.0 [86.0–206.0] days for aboBoNT-A and 32.0 [29.0–114.0] days for placebo ( P = 0.0176). Discussion/Conclusion Median time between first injection (administered in patients 2–12 weeks post-stroke, MAS ≥ 2) and appearance of reinjection criteria (signs of symptomatic spasticity) was statistically significantly longer with aboBoNT-A compared with placebo. Safety profile was consistent with the known profile of aboBoNT-A.