Randomized, placebo-controlled trial of incobotulinumtoxina for upper-limb post-stroke spasticity

Abstract

Introduction: Efficacy and safety of incobotulinumtoxinA in post-stroke upper-limb spasticity were studied.

Methods: Subjects randomized 2:1 to incobotulinumtoxinA (fixed dose 400 U) or placebo, with fixed doses for the primary target clinical pattern (PTCP; flexed elbow, 200 U; flexed wrist, 150 U; clenched fist, 100 U). Doses for non-primary patterns were flexible within predefined ranges.

Results: At week 4, incobotulinumtoxinA led to larger improvements in PTCP Ashworth scale (AS) scores than placebo [least-squares mean change ± standard error: -0.9 ± 0.06 (n = 171) vs. -0.5 ± 0.08 (n = 88); P < 0.001], and more subjects were PTCP AS responders (≥1-point improvement) with incobotulinumtoxinA (69.6%) than with placebo (37.5%; P < 0.001). Investigator's Global Impression of Change confirmed superiority of incobotulinumtoxinA vs. placebo (P = 0.003). IncobotulinumtoxinA was associated with functional improvements, as demonstrated in responder rates for Disability Assessment Scale principal target at week 4 (P = 0.007). Adverse events were mainly mild/moderate, and were reported by 22.4% (incobotulinumtoxinA) and 16.8% (placebo) of subjects.

Conclusions: IncobotulinumtoxinA significantly improved upper-limb spasticity and associated disability, and was well-tolerated.

Keywords: Xeomin; botulinum toxins, type A; incobotulinumtoxinA; muscle spasticity; stroke.

Figure 1

Subject flow diagram. FAS indicates full analysis set; SES indicates safety evaluation set.

Figure 2

Ashworth scale scores. LS mean indicates least‐squares mean. (A) Change from baseline to week 4 for the primary target clinical pattern (PTCP, full analysis set, last observation carried forward). Error bars show the standard error. ^** P < 0.001 for incobotulinumtoxinA vs. placebo. (B) Responder analysis for the PTCP over time (full analysis set, worst case imputation). Subjects with an improvement (reduction) of ≥1 point on the Ashworth scale were classified as responders. ^** P < 0.001, ^* P = 0.004 for incobotulinumtoxinA vs. placebo. (C) Responder analysis for each clinical pattern group at week 4 (full analysis set, observed cases). Subjects with an improvement (reduction) of ≥1 point on the Ashworth scale were classified as responders. ^** P ≤ 0.001, ^* P = 0.028 for incobotulinumtoxinA vs. placebo.

Figure 3

Investigator's Global Impression of Change. LS mean indicates least‐squares mean. (A) Mean scores for the primary target clinical pattern (PTCP) at week 4 (full analysis set, worst case imputation). Error bars show the standard error. ^* P < 0.05 for incobotulinumtoxinA vs. placebo. (B) Frequency distribution for the PTCP 4 weeks after treatment (full analysis set, worst case imputation). P = 0.001 (Wilcoxon rank‐sum test).