IncobotulinumtoxinA significantly reduced unstimulated salivary flow rate for patients with sialorrhea.
Wolfgang H. Jost, MD
Treatment with incobotulinumtoxinA (Xeomin) significantly reduced unstimulated salivary flow rate (uSFR) for patients with sialorrhea in patients with Parkinson disease, stroke, and other etiologies, according to findings from the phase 3 SIAXI trial.
In the trial, which was detailed in a poster at the 2018 AANEM Annual Meeting,1 incobotulinumtoxinA reduced the mean uSFR by -0.12 grams per minute at a 100U dose. There was also an improvement of 1.04 points compared with baseline in global impression of change scale (GICS) at 4 weeks with the neurotoxin. Based on these findings, in July 2018 the FDA approved incobotulinumtoxinA for the treatment of adult patients with sialorrhea, making it the only neurotoxin approved for this indication.
"In the SIAXI study, consistent reduction in salivary flow rate, and increasing improvements in clinical outcomes and quality of life, were observed with repeated injections of incobotulinumtoxinA 75 or 100 U for sialorrhea," lead author Wolfgang H. Jost, MD, and colleagues wrote in their poster. "Long-term incobotulinumtoxinA treatment for sialorrhea was well tolerated, with no major differences between the cycles. No additional safety concerns were reported."
In the study, 184 patients were randomized to received placebo (n = 36) or incobotulinumtoxinA at 75U (n = 74) or 100U (n = 74). The neurotoxin was administered at either 15U for the lower dose group or 20U for the higher into each submandibular gland and at 22.5U and 30U, respectively, into each parotid gland. Patients enrolled with sialorrhea most commonly had Parkinson disease (70.3%), followed by stroke (18.2%), atypical Parkinson syndromes (8.8%), and traumatic brain injury (2.7%).
At week 4 of the first cycle, there was a mean change from baseline of -0.07 and -0.12 for the 75U and 100U doses of incobotulinumtoxinA, respectively, compared with -0.03 for placebo. At week 16, there was a -0.06 and -0.11 drop for the smaller and larger dose, respectively, versus a 0.01 gain with placebo.
Mean uSFR continued to decline with continued incobotulinumtoxinA treatment. The study included a total of 4 cycles, each lasting 16 weeks, with repeated treatment at the beginning of each cycle. At the end of the study, the mean change in uSFR was -0.16 and -0.17 for the 75U and 100U doses, respectively. Placebo was discontinued after the first cycle.
At week 4 of the first cycle, mean changes in GICS scores from baseline were 0.47, 0.84, 1.04, for placebo, 75U, and 100U, respectively. At week 16, these scores were 0.20, 0.34, and 0.72, respectively. By the end of the study, there was a mean change from baseline of 1.29 with the 75U dose and of 1.41 with the 100U dose of incobotulinumtoxinA.
There were marked improvements with the neurotoxin in drooling severity and frequency scale (DSFS) scores. At week 4 of the first cycle, the sum DSFS score was -0.53 with placebo compared with -1.37 and -1.58 with the 75U and 100U doses, respectively. At week 4 of cycle 4, the sum DSFS score was -3.13 with the 75U dose and -3.08 with the 100U dose. Similar findings were seen for DSFS severity and frequency.
Overall, Radboud oral motor inventory for Parkinson’s disease (mROMP) scores remained stable over the course of the study. Additionally, there were consistent improvements in EQ-5D-3L scores for patients receiving incobotulinumtoxinA.
Most adverse events (AEs) were mild to moderate in severity and resolved by the end of the study. Across the 4 cycles of treatment, the most common incobotulinumtoxinA-related AEs with the 75U and 100U dose, respectively, were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%). There were no serious treatment-related AEs reported during the first cycle; however, in the full study, serious speech disorder did emerge for 1 patient treated with the 75U dose and serious dysphagia for 1 patient treated with the 100U dose.
IncobotulinumtoxinA is also approved for the treatment of upper limb spasticity (ULS), cervical dystonia (CD), and blepharospasm. A poster detailing a pooled analysis of studies conducted across these 3 indications was also presented at the 2018 AANEM meeting.2 This study showed an overall low incidence of AEs, with most being mild to moderate in severity and no serious treatment-related AEs. The pooled analysis also noted that patients did not develop neutralizing antibodies to the neurotoxin.
In studies allowing repeat dosing, there was a trend toward lower incidence of AEs with subsequent treatments. In cycle 1 for those with CD, 59.1% of patients experienced an AE, which declined to 37.7% by cycle 6. Similar findings were seen for blepharospasm (56.4% dropping to 47.2%) and ULS (24.6% dropping to 4.3%).