Safety and Stability of Pulmonary Function in Patients with Decreased Respiratory Function Treated for Spasticity with OnabotulinumtoxinA

Toxins (Basel). 2020 Oct 19;12(10):661. doi: 10.3390/toxins12100661.

Abstract

Two randomized, placebo-controlled studies evaluated the pulmonary function safety of onabotulinumtoxinA (onabotA) for treatment of upper and/or lower limb spasticity. Patients with stable baseline respiratory status received one or two treatments with placebo, 240 U, or 360 U of onabotA. Pulmonary function tests, adverse events, and efficacy were measured at least every 6 weeks for 18 weeks (Study 1) or 30 weeks (Study 2). Study 1 enrolled 109 patients (n = 36-37/group) and Study 2 enrolled 155 patients (n = 48-54/group). Mean baseline forced vital capacity (FVC) was 76-78% of predicted per group in Study 1 and 71% of predicted per group in Study 2. In Study 1, change from baseline FVC values were significantly (p < 0.05) decreased vs. placebo at weeks 3 (240 U -57 mL vs. placebo +110 mL) and 12 (360 U -6 mL vs. +167 mL placebo). In Study 2, change from baseline FVC values were significantly decreased in the 360 U group vs. placebo at weeks 6 (-78 mL vs. +49 mL placebo), 13 (-60 mL vs. +119 mL placebo), 18 (-128 mL vs. +80 mL placebo), and 24 (-82 mL vs. +149 mL placebo). Individual pulmonary function-related adverse events were not correlated with PFT decreases. The most frequent pulmonary-related adverse events were nasopharyngitis (Study 1) and upper respiratory tract infection (Study 2). Ashworth scores were significantly improved at multiple time points in both studies. Injection of onabotA for spasticity in patients with decreased pulmonary function, at single and repeated doses of up to 360 U, was associated with small but statistically significant decreases in FVC or forced expiratory volume 1 s (FEV1) (>12% and 200 mL) that were subclinical and not correlated with any adverse clinical pulmonary events.

Keywords: botulinum toxin type A; forced expiratory volume; forced vital capacity; onabotulinumtoxinA; pulmonary function testing; respiratory function; spasticity.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine Release Inhibitors / adverse effects
  • Acetylcholine Release Inhibitors / therapeutic use*
  • Botulinum Toxins, Type A / adverse effects
  • Botulinum Toxins, Type A / therapeutic use*
  • Double-Blind Method
  • Europe
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lower Extremity / innervation*
  • Lung / drug effects
  • Lung / physiopathology*
  • Lung Diseases / diagnosis
  • Lung Diseases / physiopathology*
  • Male
  • Middle Aged
  • Muscle Spasticity / diagnosis
  • Muscle Spasticity / drug therapy*
  • Muscle Spasticity / physiopathology
  • Prospective Studies
  • Time Factors
  • Treatment Outcome
  • United States
  • Upper Extremity / innervation*
  • Vital Capacity

Substances

  • Acetylcholine Release Inhibitors
  • Botulinum Toxins, Type A