Poland: Repeated injections of incobotulinumtoxinA (incoBoNT/A) are safe and effective for the treatment of sialorrhea associated with neurologic disorders in children and adolescents, according to results from the SIPEXI study.
The study, published in the journal Neurology provides Class I evidence that injection of incoBoNT/A decreases drooling in children aged 6–17 years with neurologic disorders.
Sialorrhea (drooling) is a chronic impairment that is observed commonly in children with neurodevelopmental disorders or intellectual disability and metabolic and neurodegenerative diseases. IncobotulinumtoxinA (incoBoNT/A; botulinum toxin A free from complexing proteins; Xeomin, Merz Pharmaceuticals GmbH) has been approved for the treatment of sialorrhea in adults in the United States in 2018 and in the European Union in 2019.
Steffen Berweck, Jagiellonian University, Krakow, Poland, and colleagues aimed to investigate the efficacy and safety of repeated injections of incoBoNT/A for treatment of chronic sialorrhea (drooling) associated with neurologic disorders (e.g., cerebral palsy, traumatic brain injury) or intellectual disability in children and adolescents in a prospective phase III study (SIPEXI [Sialorrhea Pediatric Xeomin Investigation]).
For this purpose, 2- to 17-year-old patients with sialorrhea due to neurologic disorders or intellectual disability were enrolled. Patients received bodyweight–dependent doses of incoBoNT/A (20–75 U). A main period with 1 injection cycle (placebo-controlled, double-blind, 6- to 17-year-olds) was followed by an open-label extension with up to 3 further cycles.
An additional cohort of 2- to 5-year-olds received active treatment throughout the study. Coprimary endpoints were the change in unstimulated salivary flow rate (uSFR) from baseline to week 4 and the carers' Global Impression of Change Scale (GICS) rating at week 4. Adverse events were recorded.
In the main period, 220 patients aged 6–17 years were randomized and treated (148 patients in incoBoNT/A group, 72 patients in the placebo group). A total of 35 patients aged 2–5 years received incoBoNT/A (no placebo). 214 patients aged 6–17 years and 33 patients aged 2–5 years continued treatment in the open-label extension period.
Key findings include:
For the 6- to 17-year-olds, a significant difference between incoBoNT/A and placebo was seen in mean uSFR decrease (difference −0.06 g/min) and the carers' GICS rating (difference 0.28 points) at week 4, in favor of active treatment.
The secondary endpoints consistently supported these results.
A sustained benefit was observed during the extension.
Incidences of adverse events were comparable between incoBoNT/A and placebo and did not increase notably with repeated injections.
The most common adverse events were respiratory infections.
Efficacy and safety were also favorable in the uncontrolled cohort of 2- to 5-year-olds.
"This study provides Class I evidence that injection of incobotulinumtoxinA decreases drooling in children aged 6 to 17 years with neurologic disorders," wrote the authors.
"Both co–primary efficacy endpoints were reached and superiority of incoBoNT/A over placebo was confirmed," they concluded. "IncoBoNT/A (up to 75 U, up to 4 cycles) is an effective and well-tolerated treatment for sialorrhea associated with neurologic disorders in children."
Reference:
Placebo-Controlled Clinical Trial of IncobotulinumtoxinA for Sialorrhea in Children SIPEXI Steffen Berweck, Marcin Bonikowski, Heakyung Kim, Michael Althaus, Birgit Flatau-Baqué, Daniela Mueller, Marta Dagmara Banach Neurology Oct 2021, 97 (14) e1425-e1436; DOI: 10.1212/WNL.0000000000012573