A Randomized, Double-Blind, Placebo Controlled, Crossover Trial of incobotulinumtoxinA Treatment for Upper Limb Tremor.

[BACKGROUND] Proximal upper limb tremor is a common, functionally disabling condition. Medical therapy is often ineffective. IncobotulinumtoxinA can significantly improve tremor with minimal adverse effects.

[OBJECTIVES] We aimed to compare clinical, functional, and quality of life measures in patients with proximal upper limb tremor following incobotulinumtoxinA treatment.

[METHODS] We undertook a double-blind, randomized two-sequence, two-period, two-treatment, placebo-controlled cross-over trial. Twenty adult patients with proximal upper limb tremor were recruited from a tertiary movement disorders clinic. Patients were randomized 1:1 to alternate electromyographically guided intramuscular injections of either incobotulinumtoxinA or saline to the dominant upper limb using computer-generated randomization. Patients were injected at baseline, then 4 months after cross-over. Primary outcome was change in Goal Attainment Rating Scale (GARS) at two-months post intervention. Secondary outcomes were dominant upper limb The Essential Tremor Rating Assessment Scale (TETRAS), Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) and three patient-related outcome measures. Outcomes were assessed at baseline and monthly intervals for 3-months post each intervention.

[RESULTS] There was no significant improvement in the GARS at 2-months post injection (OR 1.83, 95% CI 0.14-24.32). Secondary outcomes showed a mean reduction in TETRAS score of -1.05 (95% CI -1.99 to -0.13) and FTM-TRS of -6.84 (95% CI -12.37 to -1.31) in those receiving incobotulinumtoxinA. There was no significant change in patient-rated outcome scores.

[CONCLUSION] Single dose incobotulinumtoxinA injections are effective in reducing objective measures of proximal upper limb tremor and function. This did not translate into improved patient-rated outcomes in this single therapeutic dose study.