Abstract / Summary
This double-blind, placebo-controlled, phase II trial (NCT04766723) investigated the efficacy and safety of incobotulinumtoxinA (Xeomin®) in the treatment of essential tremor (ET) of the upper limb (UL). Adults with ET of the UL were randomized 2:1 (n = 78) and treated (n = 77) with intramuscular injections of incobotulinumtoxinA or placebo at semi-flexible doses into their motor-dominant arm. The primary endpoint was the change from baseline to week 6 in maximum tremor amplitude at wrist level. Baseline characteristics of treated patients were well matched across treatment arms. The primary endpoint was not met; maximum tremor amplitude at the wrist decreased from baseline to week 6 in both groups, with changes numerically favoring placebo (least squares mean treatment difference 0.21, p = 0.28). At week 6, compared with the placebo group, the incobotulinumtoxinA group had improvement in The Essential Tremor Rating Assessment Scale (TETRAS) performance dominant UL score (p = 0.006) and Quality of Life in ET (QUEST) total score (p = 0.073). However, these secondary outcomes must be interpreted descriptively as exploratory findings. Although the p-value and the 95% confidence interval including zero did not support statistical significance, the observed numerical treatment difference in change from baseline in QUEST total score suggests that the treatment effect may be consistent with the minimal clinically important difference in favor of incobotulinumtoxinA. Improvement in TETRAS Activities of Daily Living UL score was similar in both groups at week 6 (p = 0.933). IncobotulinumtoxinA was generally well tolerated. Treatment of UL ET with incobotulinumtoxinA did not show superiority over placebo for the primary endpoint. Secondary and other efficacy endpoints should therefore be viewed as exploratory, generating hypotheses suggesting potential improvements in TETRAS UL performance score and quality of life that require confirmation in further research. IncobotulinumtoxinA demonstrated a favorable safety profile without any new or unexpected safety concerns.