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IncobotulinumtoxinA, a pure botulinumtoxinA formulation, is free of accessory proteins. This analysis provides pooled safety data from phase 3 trials of children/adolescents (2-17 years), investigating incobotulinumtoxinA for the treatment of spasticity associated with cerebral palsy (at doses ≤20 U/kg (max. 500 U) per injection cycle (IC) for ≤6 ICs; three trials) or sialorrhea associated with neurologic disorders (at total doses of 20-75 U per IC for ≤4 ICs; one trial) for ≤96 weeks. Safety endpoints included the incidences of different types of treatment-emergent adverse events (TEAEs) and immunogenicity. IncobotulinumtoxinA dose groups were combined. Of 1159 patients (mean age 7.3 years, 60.4% males) treated with incobotulinumtoxinA, 3.9% experienced treatment-related TEAEs, with the most common being injection site reactions (1.3%) (both indications), muscular weakness (0.7%) (spasticity), and dysphagia (0.2%) (sialorrhea). Two patients (0.2%) experienced a treatment-related treatment-emergent serious adverse event, and 0.3% discontinued the study due to treatment-related TEAEs. No botulinumtoxinA-naïve patients developed neutralizing antibodies (NAbs) after incobotulinumtoxinA. All children/adolescents with known pre-treatment status and testing positive for Nabs at final visit ( n = 7) were previously treated with a botulinumtoxinA other than incobotulinumtoxinA. IncobotulinumtoxinA was shown to be safe, with very few treatment-related TEAEs in a large, diverse cohort of children/adolescents with chronic conditions requiring long-term treatment and was without new NAb formation in treatment-naïve patients.

The most important salivary glands are the paired parotid and submandibular glands. Adults produce 1 to 1.5 liters of saliva which are then regularly swallowed. When the act of swallowing is disturbed, salivation occurs. More rarely, the cause can be found in increased saliva production, for example, when caused through medication. Sialorrhea impairs the quality of life substantially and is frequently often socially stigmatizing. Therapy includes conservative measures such as functional dysphagia therapy, oral or transdermal application of anticholinergics, as well as, in selected cases, radiation and surgical measures. Over the last 20 years, local injection of botulinum toxin has been successfully applied in the treatment of this condition. With approval of incobotulinumtoxinA toxin for children and adults, this procedure will become the therapy of choice for chronic sialorrhea. The results of the phase III registration trials have demonstrated high efficacy and good safety of the injection treatment in both children and adults., Competing Interests: WHJ ist Berater und Referent für Pharm Allergan, Ipsen Pharma und Merz Pharmaceuticals und war PI der SIAXI-Studie. TB ist Berater für Merz Pharmaceuticals und Pharm Allergan und Referent für Merz Pharmaceuticals, Pharm Allergan und Ipsen Pharma RL ist Referent für die Merz Pharmaceuticals. BS hat keine Interessenskonflikte. AS ist Berater und Referent für die Merz Pharmaceuticals. MW ist Referent für Referent für Pharm Allergan, Ipsen Pharma und Merz Pharmaceuticals. SB erhielt Referentenhonorare von Merz Pharmaceuticals, IPSEN Pharma und Pharm Allergan und Beraterhonorare von Merz Pharmaceuticals und IPSEN Pharma., (Thieme. All rights reserved.)

Sialorrhea, uncontrolled, excessive drooling, accompanies different, mostly neurological disorders from childhood to adulthood. With incobotulinumtoxinA (Xeomin, IncoBoNT/A, Merz Pharmaceuticals GmbH), an approved medication for the treatment of sialorrhea has been available since 2019. Patient selection, possible therapy goals, treatment and the management of specific treatment situations build the focus of this interdisciplinary expert consensus recommendations with the intent to facilitate access to treatment and to contribute to qualified botulinum toxin therapy., Competing Interests: Der Inhalt dieses Konsensus-Artikels, der in interdisziplinärer Absprache und Kooperation aller Autoren entstanden ist, wurde während drei Arbeitstreffen entwickelt. Merz Pharmaceuticals hat diese Arbeitstreffen finanziell unterstützt, darüber hinaus aber keinerlei Einfluss auf Inhalt und Gestaltung des Beitrags genommen. W. Jost ist oder war als Berater und Referent für folgende Firmen tätig: Abbvie, Bial, Desitin, Ipsen, Kyowa Kirin, Merz, Stada, UCB, Zambon T. Bäumer erhielt Referenten- und Beraterhonorare von Kinderzentrum Pelzerhaken, Abbvie/Allergan, Ipsen Pharma, Merz Pharmazeutika. Er erhielt Forschungsgelder von: Deutsche Forschungsgemeinschaft (FG 2698) und Ipsen Pharma A. Bevot erhielt Berater- und Referentenhonorare von Allergan/Abbvie, Merz, Novartis U. Birkmann erhielt Beraterhonorare von Merz Pharmaceuticals C. Buhmann erhielt Referenten- und/oder Beraterhonorare von AbbVie, Bial, Desitin, Kyowa Kirin, Merz Pharmazeutika, STADA Pharm, TAD Pharma, UCB und Zambon M. Grosheva erhielt Referenten- und Beraterhonorare von Merz Pharmaceuticals, MSD und Bayer Vital O. Guntinas-Lichius erhielt Referenten- und Beraterhonorare von Merz Pharmaceuticals U. Mlynczak erhielt Referenten- und Beraterhonorare von Merz Pharmaceuticals S. Paus ist oder war als Berater und Referent für folgende Firmen tätig: Abbvie, Allergan, Bayer, Bial, Ipsen, Merz, Novartis' C. Pflug erhielt Referenten- und/oder Beraterhonorare von AbbVie, Merz Pharmaceuticals und Olympus S. Schroeder war oder ist als Berater und Referent für folgende Firmen tätig: Allergan/Abbvie, Ipsen, Merz, Proveca A. Steffen ist Berater für Merz Pharmaceuticals, Inspire Medical und ZOLL Respicardia. Er erhielt Vortragshonorare und Reisekostenunterstützung von Intersect Medical und Clinigen. B. Wilken erhielt Referentenhonorare von Abbvie/Allergan, Takeda, Novartis, Eisai S. Berweck erhielt Referentenhonorare von Merz Pharmaceuticals, IPSEN Pharma und Pharm Allergan und Beraterhonorare von Merz Pharmaceuticals und IPSEN Pharma., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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.

Botulinum toxin (BoNT) is an established treatment option to reduce hypersalivation in children with chronic neurological disorders. Objective of this study was (1) to discriminate differences in efficacy and safety of repeated interventions using BoNT with a focus on different preparations used and (2) to look for effectiveness and treatment adherence from a qualitative research perspective in this single-center cohort study. We prospectively assessed goal attainment scaling, drooling severity and frequency score and the number of towels/day before, and 4 to 8 weeks after intervention. A parent questionnaire assessed therapy-related effects on quality of life retrospectively. A total of 19 out of 34 patients received repeated injections of BoNT (106 total). Mean dose: 95 units onabotulinumtoxinA (Botox®), 2383 units rimabotulinumtoxinB (Neuro-/Myobloc®). Outcome parameters showed a distinct reduction in all treatment groups with a higher efficacy of riB. The child's need for care was reduced in 79% and social interaction improved in 84%. Main reason for discontinuation was "not enough effect" and "formation of antibodies." riB showed to be more effective in reducing hypersalivation, but antibody-formation seems to be clinically relevant. Despite clinical efficacy treatment adherence is influenced by personal and environmental factors of parents and caretakers balancing the short-term clinical benefit versus the burden of intervention., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Botulinum toxin (BTX) offers a new treatment option to reduce drooling in adults and children. Antibody formation against BTX is known to be one reason for clinical secondary non-response to this treatment. This is a case report on the development of secondary non-response to BTX type B (BTX-B) in a 15-year-old male, with bilateral dyskinetic cerebral palsy (Gross Motor Function Classification System Level IV) with additional learning disability* and microcephaly, treated for the indication of drooling. After three successful treatment sessions, the fourth and fifth injections showed no clinical response. This was associated with the presence of antibodies against BTX-B as determined using the mouse diaphragm assay. Thus, formation of neutralizing antibodies against BTX-B appears to be an important issue, not only in patients treated for cervical dystonia but also in children treated for drooling. Subsequent injections with an adequate dose of BTX type A (BTX-A) did not show any clinical response either, although no antibodies to BTX-A were detected. Besides the unanswered questions of dosing and distribution, a second possible explanation could be that BTX-B gave rise to non-neutralizing antibodies that cross-react with BTX-A. The resulting immune complexes could be taken up by phagocytes and, thereby, impede clinical response.