IncobotulinumtoxinA May Reduce Sialorrhea in Parkinson’s Disease

LOS ANGELES—IncobotulinumtoxinA may treat sialorrhea in Parkinson’s disease and other neurologic disorders effectively, according to a trial described at the 70th Annual Meeting of the American Academy of Neurology. The treatment effect may persist for as long as 16 weeks.

Various neurologic disorders, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), may cause troublesome sialorrhea. Olaf Michel, PhD, Vice Chair of the Department of Otorhinolaryngology at the University Hospital Brussels, and colleagues conducted a phase III trial to investigate the safety and efficacy of incobotulinumtoxinA as a treatment for sialorrhea.

Olaf Michel, PhD

The researchers enrolled 184 participants (age 18 to 80) with chronic troublesome sialorrhea resulting from Parkinson’s disease or atypical parkinsonism, stroke, or traumatic brain injury (TBI) into the trial. They randomized participants in a double-blinded fashion to 75 U of incobotulinumtoxinA (ie, the low-dose group), 100 U of incobotulinumtoxinA (ie, the high-dose group), or placebo. The low-dose group received 15 U in each submandibular gland and 22.5, in each parotid gland. The high-dose group received 20 U in each submandibular gland and 30 U in each parotid gland. Follow-up lasted for 16 weeks after injection. The study’s primary outcomes were unstimulated salivary flow rate (uSFR) at week four, compared with baseline, and Global Impression of Change Scale (GICS) at week four.

In all, 74 participants were randomized to the low dose, 74 to the high dose, and 36 to placebo. The three groups were well balanced, but the proportion of women in the placebo group was lower than that in the treatment groups. Sialorrhea was associated with Parkinson’s disease in 70.6% of patients, atypical Parkinson syndromes in 8.7%, stroke in 17.9%, and TBI in 2.7%.

The investigators localized injection sites using anatomical landmarks in 39.2% of the low-dose group, 44.6% of the high-dose group, and 50% of the placebo group. They used ultrasound guidance to localize injection sites in 60.8% of the low-dose group, 55.4% of the high-dose group, and 50% of the placebo group.

At week four, changes in uSFR and GICS were similar in the placebo and low-dose groups. Improvements in these measures reached statistical significance in the high-dose group at week four, however. At weeks eight through 12, the improvements in uSFR and GICS in both active treatment groups were significant. Improvements in the uSFR and GICS in both dose groups were maintained at week 16, but were lower in the low-dose group than in the high-dose group. Dr. Michel and colleagues observed no relevant differences in outcomes according to the technique used to localize injection sites. They also observed no unexpected side effects.

At the end of the 16-week study, all patients entered a 48-week extension period during which they received three additional injections of dose-blinded incobotulinumtoxinA at 16-week intervals. The treatment effect stabilized and did not decline during the extension, and the investigators observed no accumulation of adverse events.