A critical review of incobotulinumtoxinA in the treatment of chronic sialorrhea in pediatric patients

ABSTRACT

Introduction

Sialorrhea, also known as hypersalivation, ptyalis, or drooling, results in physical and psychosocial complications that may have a significant negative impact on quality of life for both the patient and their caregiver. The goal of pharmacological treatment is to reduce excessive salivary flow, while maintaining a moist and healthy oral cavity; until recently, however, few of the agents used to treat chronic sialorrhea have been approved in pediatric patients.

Areas covered

This article summarizes early evidence for the use of botulinum neurotoxin A formulations in the treatment of children/adolescents with chronic sialorrhea, and findings of the recently completed phase III trial of incobotulinumtoxinA in this indication. Alternative therapies are also briefly discussed.

Expert opinion

IncobotulinumtoxinA is the first botulinum neurotoxin A to be approved for the treatment of chronic sialorrhea in children and adults, following the results of phase III trials that demonstrate the efficacy and safety of the drug in these patients. The authors expect that the positive findings will result in updates to clinical guidelines for the treatment of children with chronic sialorrhea.

Abbreviations

AE, adverse event; AESI, adverse event of special interest; BoNT/A, botulinum neurotoxin A; CI, confidence interval; CP, cerebral palsy; DIS, drooling impact scale; DQ, drooling quotient; DSFS, Drooling Severity and Frequency Scale; GICS, Global Impression of Change Scale; LS, least squares; mTDS, modified Teacher’s drooling scale; NR, not reported; PD, Parkinson’s disease; SAE, serious adverse event; SE, standard error; SIAXI, Sialorrhea in Adults Xeomin Investigation; SIPEXI, Sialorrhea Pediatric Xeomin Investigation; SNAP-25, synaptosomal associated protein-25; TBI, traumatic brain injury; TDS, Teacher Drooling Scale; USA, United States of America; uSFR, unstimulated Salivary Flow Rate; VAS, visual analog scale

KEYWORDS:

• Botulinum neurotoxin A
• chronic sialorrhea
• hypersalivation
• incobotulinumtoxinA
• pediatric

Article highlights

• Sialorrhea occurs when there is excessive production of saliva or an inability to transport saliva out of the oral cavity; it can have a significant negative impact on quality of life for both the patient and their caregiver

• It is generally accepted that the management of sialorrhea is best accomplished with a multidisciplinary team approach, but there are limited reliable study data to support use of the different therapies that are currently used for treating sialorrhea in children

• IncobotulinumtoxinA has shown good efficacy and safety after single and repeated injection cycles in a relatively large phase III trial of children/adolescents with chronic sialorrhea, resulting in its approval for pediatric sialorrhea in the USA

• Injection of botulinum neurotoxin A is best achieved using ultrasound to guide needle insertion

• IncobotulinumtoxinA may be a valuable treatment option for chronic sialorrhea because it has a similar treatment schedule in affected children and adults, and has demonstrated ongoing efficacy and safety after multiple injection cycles in phase III trials in both populations

• Further research to evaluate the combination of incobotulinumtoxinA with glycopyrrolate for specific saliva stimulating situations would be of interest, as would determination of which patients will likely obtain the greatest benefit from incobotulinumtoxinA, and investigation of incobotulinumtoxinA treatment in patients with posterior drooling.

Acknowledgments

The authors would like to thank Clara Jost, who was available as a model for the photos, and Mr. David Kühn, KVM Verlag, who supported the adaptation of the anatomy photo, and acknowledge Caroline Spencer and Dr. Sue Chambers (Rx Communications, Mold, UK) for medical writing assistance with the preparation of this manuscript, funded by Merz Pharmaceuticals.

Declaration of interests

WH Jost, A Steffen, and S Berweck are advisors and speakers for Merz Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this article has participated in research funded by the Parkinson Foundation, Tourette Association, Dystonia Coalition, AbbVie, Boston Scientific, Eli Lilly, Neuroderm, Prilenia, Revance, Teva but has no owner interest in any pharmaceutical company. They have received travel compensation or honoraria from the Tourette Association of America, Parkinson Foundation, International Association of Parkinsonism and Related Disorders, Medscape, and Cleveland Clinic, and royalties for writing a book with Robert Rose publishers. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Information resources

The following website provides support and resources for pediatric patients with sialorrhea and their caregivers: https://www.rch.org.au/uploadedFiles/Main/Content/plastic/salivabook.pdf.

The following website provides guidance for clinicians treating children/youth with cerebral palsy and sialorrhea, and provides an evidence-based care pathway for those affected: https://www.aacpdm.org/publications/care-pathways/sialorrhea.

The National Institute for Health and Care Excellence published an evidence summary for severe sialorrhea in children and young people with chronic neurological disorders with a focus on oral glycopyrrolate in 2017: https://www.nice.org.uk/advice/es5/resources/severe-sialorrhoea-drooling-in-children-and-young-people-with-chronic-neurological-disorders-oral-glycopyrronium-bromide-pdf-32176358341.

Updated German guidelines for the treatment of hypersalivation have been published [9].

The following book provides a comprehensive overview of the proper use of botulinum toxin in a number of indications: Wolfgang Jost. Atlas of Botulinum Toxin Injection, Dosage, Localization, Application, 3rd Edition. 2019. Quintessence Publishing, United Kingdom.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

Medical writing assistance with the preparation of this manuscript was funded by Merz Pharmaceuticals.