Doses Of incobotulinumtoxinA Research Articles

Goal Attainment and Ambulation With Increasing Doses of IncobotulinumtoxinA: A Post Hoc Analysis of the TOWER Study

Goal Attainment and Ambulation With Increasing Doses of IncobotulinumtoxinA: A Post Hoc Analysis of the TOWER Study

Pooled Safety Analysis of IncobotulinumtoxinA in the Treatment of Neurological Disorders in Adults

The pooled incidences of treatment-emergent adverse events (TEAEs) were examined by indication using the integrated clinical database of Merz-sponsored, placebo-controlled, or repeat-dose studies of incobotulinumtoxinA in adults with cervical dystonia, blepharospasm, limb spasticity, sialorrhea, or essential tremor of the upper limb. Overall incidences of TEAEs, serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (TEAESIs; indicating possible toxin spread), and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection and for repeated dose cycles of incobotulinumtoxinA. The most frequent events after a single dose of incobotulinumtoxinA are summarized. After a single cycle, incidences of overall TEAEs were similar between incobotulinumtoxinA and the placebo in most indications, although between-indication differences were observed. Few TEAEs led to incobotulinumtoxinA discontinuation; there were no fatal TEAEs with incobotulinumtoxinA. In general, repeated cycles did not increase the incidence of any event. The most frequent TR-TEAEs were indication-dependent, including dysphagia for indications affecting the head or neck. The TR-TEAESIs across all indications were most commonly muscular weakness, dysphagia and dry mouth. Overall, the results of this pooled analysis support and extend the favorable safety and tolerability profile of incobotulinumtoxinA for the treatment of adult neurological disorders established by individual clinical studies.

Spasticity-related pain in children/adolescents with cerebral palsy. Part 2: IncobotulinumtoxinA efficacy results from a pooled analysis.

This pooled analysis of data from three Phase 3 studies investigated the effects of incobotulinumtoxinA on spasticity-related pain (SRP) in children/adolescents with uni-/bilateral cerebral palsy (CP). Children/adolescents (ambulant and non-ambulant) were evaluated for SRP on increasingly difficult activities/tasks 4 weeks after each of four incobotulinumtoxinA injection cycles (ICs) using the Questionnaire on Pain caused by Spasticity (QPS; six modules specific to lower limb [LL] or upper limb [UL] spasticity and respondent type [child/adolescent, interviewer, or parent/caregiver]). IncobotulinumtoxinA doses were personalized, with all doses pooled for analysis. QPS key item responses were available from 331 and 155 children/adolescents with LL- and UL-spasticity, respectively, and 841/444 (LL/UL) of their parents/caregivers. IncobotulinumtoxinA efficacy was evident with the first IC. Efficacy was sustained and became more robust with further subsequent ICs. By Week 4 of the last (i.e. fourth) IC, 33.8-53.3% of children/adolescents reported complete SRP relief from their baseline pain for respective QPS items. Children/adolescents reported reductions in mean LL SRP intensity at levels that surpassed clinically meaningful thresholds. Similarly, parents/caregivers observed complete SRP relief and less frequent SRP with incobotulinumtoxinA. Similar results were found for UL SRP. These findings indicate that incobotulinumtoxinA could bring considerable benefit to children/adolescents with spasticity by reducing SRP, even during strenuous activities.

The use of IncobotulinumtoxinA in spastic forms of cerebral palsy: a review of randomized clinical trials

Botulinum therapy has been used to treat increased muscle tone and spasticity in cerebral palsy (CP) over almost 30 years. Despite this, every year a large number of published scientific articles present new clinical studies devoted to various aspects of the use of botulinum toxin type A (BTA) products in children. The article discusses in detail the results of three major international randomized clinical trials concerning determination the efficacy and safety of the product Xeomin (IncobotulinumtoxinA) in spastic forms of cerebral palsy. All these studies were performed in accordance with the criteria of evidence-based medicine - randomized, prospective, multicenter, comparative, and longitudinal with a large number of patients, clear inclusion and exclusion criteria. The TIM (Treatment with incobotulinumtoxinA in Movement) study demonstrated the effectiveness of the treatment of spasticity of the lower extremities muscles when using different doses of IncobotulinumtoxinA (8, 6 and 2 units/kg of body weight to correct one pathological pattern) in a double-blind study. The TIMO (Treatment with IncobotulinumtoxinA in Movement Open Label) study showed the efficacy and safety of high doses of IncobotulinumtoxinA (total doses of 16-20 units/kg of body weight) in the treatment of spasticity of the lower and upper extremities with prolonged use. The XARA study (IncobotulinumtoxinA in Arm Treatment in Cerebral Palsy) presented data on the high efficacy of IncobotulinumtoxinA when using a multi-level approach for the treatment of lower and upper limb spasticity in CP children and adolescents, which reflects the real clinical needs of a large number of patients. In each of these studies, the safety of the use of IncobotulinumtoxinA was also evaluated. Good tolerability of therapy was demonstrated (84.1% of patients completed all visits in total according to three studies - TIM, TIMO and XARA) and its safety (the frequency of adverse events associated with therapy was observed in less than 2% of cases). Treatment with IncobotulinumtoxinA was characterized by the lack of an immunologic response - Xeomin as a starting therapy provides a stable effect without fading associated with the development of neutralizing antibodies.

Safety Profile and Lack of Immunogenicity of IncobotulinumtoxinA in Pediatric Spasticity and Sialorrhea: A Pooled Analysis.

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.

Russian consensus on the use of incobotulinumtoxinA in children with cerebral palsy for the treatment of spasticity and sialorrhea

Botulinum therapy for cerebral palsy (CP) is considered not only as one of the effective approaches for the treatment of increased muscle tone and spasticity, but also as a method of excessive salivation correction. The article presents an overview of the results of Russian and foreign studies on the efficacy and safety of incobotulinumtoxinA for the treatment of spasticity of the lower and upper limbs, as well as sialorrhea in patients with CP. The article also provides a consensus opinion of Russian specialists working with patients with CP and using Xeomin (incobotulinumtoxinA) in their practice for the treatment of spasticity and sialorrhea. This consensus was based on the results of a Russian retrospective multicenter study on the use of incobotulinumtoxinA for the treatment of spasticity and sialorrhea in CP, data from recently published international clinical trials, and our own clinical experience. We present detailed practical recommendations on the calculation of the total dose of incobotulinumtoxinA per procedure for the treatment of spasticity in CP, on the calculation of incobotulinumtoxinA dose for the most common target muscles (lower and upper limbs) for spasticity treatment in CP, on incobotulinumtoxinA dilution and dose calculation for sialorrhea treatment in children, on incobotulinumtoxinA dilution and dose calculation for simultaneous treatment of spasticity and sialorrhea in CP. We justify incobotulinumtoxinA use, when simultaneous treatment of spasticity and sialorrhea is necessary, which allows reducing the intervals between repeated injection cycles. IncobotulinumtoxinA use in children with CP demonstrates a favorable safety profile, including long-term use.

Management of Spasticity Caused by Thrombotic Brain Injury with Incobotulinumtoxina in a Young Patient: A New Paradigm

Case: Acquired brain damage is one of the most complex pathologies that affect the central nervous system, there is great variability in its pathophysiology, from traumatic focal injuries to diffuse axonal injuries, including spasticity. It supposes a great comorbidity and functional repercussion in patients, hindering their subsequent recovery. We report a case of a young patient with a history of quadriplegia due to acquired brain damage secondary to thrombosis of the dural sinus. The patient presented sensorimotor deficit, restricted function, and a great situation of dependency. He required three cycles of high doses of incobotulinumtoxinA (IncoBoNT) according to his specific need, the first infiltration was 800 U, the second 800 U, and the last 500 U over a period of 14 weeks. Thanks to the previous objectives agreement with the patient the results were satisfactory and relevant for him, presenting a great functional improvement of spasticity and associated pain, as assessed by the visual analog scale score.Conclusion: IncoBoNT at high doses and short intervals has been shown to be an effective and valuable tool for personalized treatment adapted to the needs of severely affected neurological patients.

Real Life Experience with Individualized Doses of Incobotulinumtoxina in Patients with Severe Spasticity Due to Acquired Brain Injury

The objective of the present study was to evaluate the effectiveness and tolerability of incobotulinumtoxinA, at doses according to individual needs, in 10 patients with acquired brain injury and severe upper and lower limb spasticity. Patients received a multipattern periodic treatment with ultrasound-guided injections of incobotulinumtoxinA at doses of 800-900 U in the upper and lower limbs. The mean number of injection cycles per patient was 4.2. The 0-10 visual analogue scale for pain score decreased significantly from pre-injection (mean: 4.7) to four-week post-injection (mean: 0.7). Similarly, the mean Ashworth Scale score (muscular tone assessment) at four-week post-injection (mean: 1.4) was significantly lower than at injection (mean: 2.5). Except for two patients in one pattern, all cases showed an improvement in passive range of motion assessments using goniometry. All patients reported maximum satisfaction with the treatment, all reporting “much improved” after the treatment. No treatment-related adverse effects were observed during the study. Individualized doses of incobotulinumtoxinA are effective and well-tolerated for this type of patients and allow better management of their severe spasticity. Therefore, individualization of doses should be taken into account for optimizing clinical outcomes and improving the patients’ treatment satisfaction.

Dose selection of Incobotulinumtoxin A for the treatment of spasticity and sialorrhea in cerebral palsy: results of a retrospective multicenter study

Introduction. In patients with infantile cerebral palsy (CP), botulinum therapy is used to treat both muscle tone disorders and sialorrhea. Therefore, it is logical to use one preparation of botulinum toxin type A to treat spasticity and sialorrhea in one injection procedure. The aim of the work is to conduct a retrospective analysis of data from 15 centres that treat patients with cerebral palsy and use the botulinum therapy method to determine the optimal doses of IncobotulinumtoxinA (IBTA) for the treatment of spasticity and chronic sialorrhea in real clinical practice. Materials and methods. The treatment results of 389 children with cerebral palsy (including 211 (54.2%) boys) with IBTA were analyzed. The majority were children with bilateral forms of cerebral palsy - 312 (80.2%). The average age of the patients was 5.27 ± 3.71 years, the average weight of the patients was 18.8 ± 10.9 kg. Results. The total dose of IBTA in the group of 389 patients with cerebral palsy for the treatment of spasticity was 163.74 ± 80.65 U (25-550; 95% CI 155.7-171.7) and 10.4 ± 5.4 U/kg body weight (1,25-29.7; 95% CI 9.8-10.9). The total dose of IBTA in the group of patients with cerebral palsy with simultaneous treatment of spasticity and chronic sialorrhea (n = 16) was significantly higher: 267.18 ± 124.57 U (115-570; 95% CI 200.8-333.6) and 13, 0 ± 7.1 U/kg (5.8-24.6; 95% CI 9.2-16.8). In the lower extremities, the most frequent target muscles were the gastrocnemius (55.0% of cases; 95% CI 49.9-60.0) and semitendinosus / semimembranous muscle (46.3% of cases; 95% CI 41.2-51.4 ), and in the upper limbs - pronator teres (48.6% of cases; 95% CI 43.5-53.7) and biceps brachii (28.8% of cases; 95% CI 24.3-33.6). Limitations of the study. The limitations of our work are the use of an open retrospective study format, a relatively small sample of patients with chronic sialorrhea, the absence of long-term follow-up of patients and the results of repeated IBTA injections. Conclusion. If it is necessary to use botulinum therapy for the treatment of spasticity and sialorrhea in a child with CP, it is optimal to use the product IncobotulinumtoxinA, which will allow correction of two pathological manifestations in one procedure and can shorten the intervals between repeated injection cycles.

Botulinum Toxin Type A for Glabellar Frown Lines: What Impact of Higher Doses on Outcomes?

Botulinum toxin serotype-A (BoNT-A) preparations are widely used to improve the appearance of wrinkles. While effective and well tolerated, patients require retreatment over time to re-establish the effects. There is growing interest from patients as to whether higher doses can prolong response without significantly increasing side effects. We reviewed the efficacy and safety evidence for high-dose BoNT-A treatment of glabellar lines, by evaluating high-dose studies published since 2015. Toxins approved for glabellar line treatment in the US or Europe were considered. “High-dose” indicated doses above the licensed dose for each BoNT-A preparation. Five studies met the inclusion criteria and most were randomized, double-blind trials; designs and population sizes varied. Findings suggested that higher-dose BoNT-A treatment is feasible and may improve response duration without increased safety issues. Around 9 months’ median duration was achieved with a 2–2.5-fold increase of the abobotulinumtoxinA on-label dose, or with a 5-fold increase in incobotulinumtoxinA dose. A 2–4-fold increase of the onabotulinumtoxinA on-label dose yielded a median duration of around 6 months. Importantly, patient satisfaction and natural look remained with increasing abobotulinumtoxinA doses. While more data are needed, these findings may lead to more effective, individually tailored treatment plans to meet patient expectations.

IncobotulinumtoxinA demonstrates safety and prolonged duration of effect in a dose-ranging study for glabellar lines

Background To further explore clinical trial results indicating increasing doses of botulinum toxin A prolong duration of effect, a 2-stage, phase 2, randomized, double-blind study investigated the duration of effect and safety of incobotulinumtoxinA (INCO; Xeominr, Bocouturer) doses higher than the US Food and Drug Administration-approved 20 units (U) for glabellar frown lines (GFL). The stage 1 primary efficacy and safety results were reported previously. Here, we report the results of the final analysis (stage 1 and 2), including primary and secondary efficacy and safety endpoints. Methods A total of 241 subjects with moderate-to-severe GFL were randomized to receive a single treatment with 20 (N=61), 50 (N=60), 75 (N=61), or 100U (N=59) INCO. The primary efficacy endpoint was duration of g 1-point improvement from baseline assessed by investigator at maximum frown on the Facial Wrinkle Scale. Results The median duration of effect was 175 days for the 20U group (95% CI 142, 185), 185 days for the 50U group (95% CI 182, 205), 210 days for the 75U group (95% CI 182, 217), and 215 days for the 100U group (95% CI 183, 237). The incidence of treatment-related adverse events was low across all doses and there were no treatment-related serious adverse events. Conclusions These results demonstrate that all INCO doses were well tolerated, consistent with the known safety profile of 20U, and increasing dose prolongs the duration of effect for GFL. J Drugs Dermatol. 2021;20(10):1052-1060. doi:10.36849/JDD.6377THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study

In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn–Tolosa–Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, n = 19; placebo, n = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 (p = 0.003) and Week 8 (p = 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 (p < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 (p = 0.004) and Week 8 (p < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.

IncobotulinumtoxinA for the treatment of spasticity in children with cerebral palsy \u2013 a retrospective case series focusing on dosing and tolerability

BackgroundIncobotulinumtoxinA (Xeomin®) is a botulinum neurotoxin type A with established efficacy in the treatment of upper-limb spasticity in adults. This retrospective case series in a university hospital setting aimed to elucidate the safety and tolerability of incobotulinumtoxinA for treatment of spasticity in children with cerebral palsy.MethodsParticipants received incobotulinumtoxinA injections up to a maximum total dose of 600 U, 24 U/kg body weight. Medical records were reviewed for key demographic information, incobotulinumtoxinA exposure, and adverse effects (AEs).ResultsSixty-nine children were included (mean age [SD], 8.3 [3.9] years; 44/69 [63.8%] male). One-hundred-and-ninety-one injections were administered, with mean (SD) of 2.8 (1.5) treatment cycles/participant and dosing interval of 6.0 (1.7) months. The number of muscles injected increased from 2.4 (1.2) at cycle 1 to 4.2 (1.9) at cycle 6. The mean (SD) total incobotulinumtoxinA dose increased from 191.7 (126.2) U, (8.5 [5.4] U/kg body weight) at cycle 1 to 368.0 (170.1) U, (9.9 [5.5] U/kg body weight) at cycle 6. Seventy four adverse effects (37.5% of injections) were reported, the most frequent was injection pain (93.2% of AEs). Only three AEs were considered directly treatment-related by injectors: muscle weakness, generalized weakness, and fever.ConclusionsOur clinical experience indicates that incobotulinumtoxinA is a well-tolerated treatment option for focal spasticity in children with cerebral palsy.Trial registrationAs the study was observational and retrospective, no EudraCT registration number was requested. The internal code assigned to the study in the administrative resolution was: 1143-N-15.

Quality of life in subjects with upper- and lower-limb spasticity treated with incobotulinumtoxinA

BackgroundWe evaluated quality of life among subjects with upper- and lower-limb spasticity who received escalating doses of incobotulinumtoxinA (total body doses up to 800 U) in the prospective, single-arm, dose-titration TOWER study.MethodsIn this exploratory trial, subjects (N = 155; 18–80 years of age) with upper- and lower-limb spasticity due to cerebral causes who were deemed to require total body doses of up to 800 U incobotulinumtoxinA received three consecutive injection cycles of incobotulinumtoxinA (400, 600, and up to 800 U), each with 12 to 16 weeks’ follow-up. QoL was assessed using the EuroQol 5-dimensions questionnaire, three-level (EQ-5D), before and 4 weeks post-injection in each injection cycle and at the end of injection cycle 3.ResultsThe mean EQ-5D visual analog scale scores of 155 participants continuously improved from study baseline to 4 weeks post-injection in all injection cycles (mean [standard deviation] change 6.7 [14.1], 9.6 [16.3], and 8.6 [17.0] for injection cycles 1, 2, and 3, respectively; p < 0.0001 for all, paired sample t-test). In general, among those with a change in the EQ-5D rating of their condition, the proportion of subjects with ‘improvement’ was greater than that with ‘worsening’ for individual EQ-5D dimensions across all injection cycles. At the end of injection cycle 3, the proportion of subjects rating their condition as ‘normal’ increased from study baseline for all dimensions, and there was a ≥ 46% reduction in the proportion of subjects with a rating of ‘severe impairment’.ConclusionThese preliminary results suggest that escalating incobotulinumtoxinA doses up to 800 U are associated with improvement in quality of life ratings in subjects with multifocal upper- and lower-limb spasticity, and form a basis for future comparator studies.Trial registrationClinicalTrials.gov, NCT01603459. Date of registration: May 22, 2012.

Post hoc analysis of the improvement in shoulder spasticity and safety observed following treatment with incobotulinumtoxinA.

The Titration study in lOWer and uppER-limb spasticity (TOWER) study (NCT01603459), evaluated incobotulinumtoxinA for upper- and lower-limb spasticity. This post hoc analysis assessed shoulder spasticity in patients who received injections into the shoulder. Subjects received 3 injection cycles with escalating incobotulinumtoxinA doses on the same side (400, 600, 600-800 U; ≤ 600 U per limb including optional shoulder dose, planned range 100-250 U). Joint function was assessed with the Ashworth Scale shoulder sumscore (AS-SSS) in subjects treated in the shoulder vs those who were not. Safety was assessed in subjects treated in the shoulder, and in those who had upper-limb treatment without shoulder treatment. The proportion of subjects receiving shoulder treatment increased with escalating dose at each cycle (n = 84/140 (60.0%) by cycle 3; mean (standard deviation (SD)) shoulder dose 118.4 U (SD 60.2)). From baseline to 4-weeks post-injection, mean AS-SSS improved by -1.1 (SD 1.9), -1.7 (SD 1.8) and -1.7 (1.8) in cycles 1, 2 and 3, respectively, in subjects treated in the shoulder, and -0.5 (SD 1.3), -0.8 (SD 1.6) and -0.9 (SD 1.4) in subjects who were not. A significant dose effect on AS-SSS was observed in cycle 3 (p = 0.0081). No unexpected safety concerns were reported. The results demonstrate an improvement in shoulder spasticity and safety following incobotulinumtoxinA treatment.

SIAXI: Placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea.

ObjectiveThis pivotal phase III study, SIAXI, investigated the efficacy and safety of incobotulinumtoxinA for the treatment of chronic sialorrhea due to Parkinson disease (PD), atypical parkinsonism, stroke, or traumatic brain injury (TBI).MethodsAdult patients with PD (70.7%), atypical parkinsonism (8.7%), stroke (19.0%), or TBI (2.7%) were randomized (2:2:1) to double-blind treatment with placebo (n = 36), or total doses of incobotulinumtoxinA 75 U (n = 74) or 100 U (n = 74), in a single treatment cycle. The coprimary endpoints were change in unstimulated salivary flow rate from baseline to week 4, and patients' Global Impression of Change Scale score at week 4. Adverse events were recorded throughout.ResultsA total of 184 patients were randomized. Both incobotulinumtoxinA dose groups showed reductions in mean unstimulated salivary flow rate at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.004). Patients' Global Impression of Change Scale scores also improved at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.002). A lasting effect was observed at week 16 post injection. The most frequent treatment-related adverse events in the incobotulinumtoxinA 75 U and 100 U groups were dry mouth (5.4% and 2.7% of patients) and dysphagia (2.7% and 0.0% of patients).ConclusionsIncobotulinumtoxinA 100 U is an effective and well-tolerated treatment of chronic sialorrhea in adults.ClinicalTrials.gov identifierNCT02091739.Classification of evidenceThis study provides Class I evidence that incobotulinumtoxinA reduces salivary flow rates in patients with chronic sialorrhea due to PD, atypical parkinsonism, stroke, or TBI.

Safety and treatment results using high doses of incobotulinumtoxinA in patients with spasticity

Safety and treatment results using high doses of incobotulinumtoxinA in patients with spasticity

Escalating doses of incobotulinumtoxinA for extended treatment of glabellar frown lines: safety and efficacy results from a randomized, double-blind study

Escalating doses of incobotulinumtoxinA for extended treatment of glabellar frown lines: safety and efficacy results from a randomized, double-blind study

Breaking a dogma: High doses of incobotulinumtoxinA to treat severe limb spasticity with complex clinical patterns: A retrospective, multicenter study

Breaking a dogma: High doses of incobotulinumtoxinA to treat severe limb spasticity with complex clinical patterns: A retrospective, multicenter study

Efficacy of incobotulinumtoxin a in treatment of lower-limb spasticity, including pes equinovarus, in adults

The TOWER study ( NCT01603459 ) previously demonstrated that escalating doses of incobotulinumtoxinA (400–≤800 U) in patients with upper- (UL) and lower-limb (LL) spasticity due to stroke or other cerebral causes increased treatment efficacy without compromising safety or tolerability (Wissel, Neurology 2017). This post-hoc analysis assessed the efficacy of incobotulinumtoxinA for LL spasticity, including pes equinovarus. Patients received treatment with escalating total incobotulinumtoxinA doses on the same body side during three injection cycles (ICs) (400 U, 600 U and 600–800 U, respectively; maximum 600 U per limb; optional pes equinovarus, planned dose range 100–400 U). Outcomes included change from IC baseline to 4 weeks post-injection in Ashworth Scale (AS) for the ankle joint (in patients treated for pes equinovarus or not) and LL resistance to passive movement scale (REPAS) scores (in patients treated in the LL [with/without UL treatment], or UL only). In total, 155 patients were enrolled. In IC1, IC2 and IC3, respectively, 109, 137 and 137 patients received LL treatment with mean (standard deviation [SD]) total limb doses of incobotulinumtoxinA: 191.7 (97.6), 254.0 (111.6) and 320.9 (127.6) U. Pes equinovarus was treated in 88, 117 and 122 of these patients. The mean (SD) improvement in ankle joint AS score at 4 weeks post-injection was –0.66 (0.77), –0.70 (0.82) and –0.82 (0.77) in patients treated for pes equinovarus, and –0.21 (0.64), –0.38 (0.85) and –0.61 (0.70) in patients who were not, with a significant difference between the groups in IC1 ( P = 0.0006). For all ICs, the mean improvement in REPAS LL scores 4 weeks post-injection was greater in patients who were treated in the LL than in patients treated in the UL only, with significant differences between groups in IC1 ( P < 0.0001) and IC2 ( P = 0.0043). Results suggest that incobotulinumtoxinA is effective for treating LL spasticity, including pes equinovarus.