Safety Of incobotulinumtoxinA Research Articles

IncobotulinumtoxinA in refractory temporomandibular disorder due to disk dislocation: A prospective study

IntroductionTemporomandibular disorders (TMD) may include conditions involving the temporomandibular joint and/or masticatory muscles. Approximately 20 % of patients are refractory to first-line therapies. This study aims to evaluate the effects and safety of incobotulinumtoxinA in the treatment of refractory TMD due to disk dislocation. Material and methodsA quasi-experimental one-arm prospective study was conducted. Target population included individuals with a diagnosis of TMD due to disk dislocation. Patients were treated with electromyography or ultrasound guided injection of incobotulinumtoxinA in the masticatory muscles (20 U into each masseter and pterygoideus lateralis). Pain was assessed using the pain numerical rating scale, maximum unassisted mouth opening was measured in mm, and adverse events were registered at baseline, week 4, week 12 and week 24 post-treatment. Statistical analysis used the Wilcoxon test for the comparison of paired samples and the Mann-Whitney U test for independent samples, considering a p-value ≤ 0.05 as significant. Results51 patients with 75 painful temporomandibular joints due to disk dislocation (38 with reduction and 37 without) were included. A significant reduction in pain from a pre-treatment mean of 6.08/10 to a post-treatment mean of 2.04/10 (week 4), 3.18/10 (week 12), and 3.65/10 (week 24) was observed (p < 0.001). A significant decrease in maximum unassisted mouth opening from a pre-treatment mean of 36.45 mm to a post-treatment mean of 32.29 mm at week 4 was observed (p < 0.001). DiscussionBotulinum toxin injection of the masticatory muscles is safe and seems equally effective in reducing pain in patients with refractory TMD due to disk dislocation.

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.

Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Lower Limb Spasticity in Japanese Subjects.

ObjectiveTo confirm the efficacy and safety of incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH; total dose 400 U) in Japanese subjects with lower limb (LL) poststroke spasticity using the Modified Ashworth Scale spasticity score for the plantar flexors (MAS-PF).MethodsThis phase III study (Japic clinical study database No. CTI-153030, 7 October 2015) included a double-blind, 12-week main period (MP) in which 208 subjects were randomized to receive one injection cycle of incobotulinumtoxinA 400 U (n = 104) or placebo (n = 104) in the pes equinus muscles, and an open-label extension (OLEX) that enrolled 202 subjects who received three injection cycles, 10–14 weeks in duration (the last cycle was fixed at 12 weeks). Changes in MAS-PF for incobotulinumtoxinA vs. placebo from baseline to Week 4 of the MP and to the end-of-cycle visits in the OLEX were evaluated.ResultsThe area under the curve for the change in MAS-PF was statistically significantly greater with incobotulinumtoxinA vs. placebo in the MP (mean: −7.74 vs. −4.76; least squares mean: −8.40 vs. −5.81 [p = 0.0041]). In the OLEX, mean changes in MAS-PF from baseline to end-of-study showed continued improvement with repeated injections. No new safety concerns were observed with the incobotulinumtoxinA treatment. Its efficacy and safety were consistent regardless of the length of the injection cycle interval in the OLEX.ConclusionThis study demonstrated that incobotulinumtoxinA (total dose 400 U) is an effective and a well-tolerated treatment for LL spasticity in Japanese subjects using flexible injection intervals of 10–14 weeks.

Retrospective study of the clinical effect of incobotulinumtoxinA for the management of myofascial pain syndrome in refractory patients

The aim was to evaluate the effectiveness and safety of IncobotulinumtoxinA (IncoA) for the management of myofascial pain syndrome (MPS) in refractory patients. This single-center, observational, retrospective study includes 37 patients. The pain reduction was 4.7 points (95%CI: 5.6 to −3.8) from baseline to one-month post-injection (using a 10-point visual analogue scale). Only 18.9% experienced mild adverse events. In conclusion, IncoA is an effective and safe alternative for the treatment of MPS in refractory patients.

IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines.

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; Xeomin&reg;, Bocouture&reg;) 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. 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 &ge; 1-point improvement from baseline assessed by investigator at maximum frown on the Facial Wrinkle Scale. 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. 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.

Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Lower Limb Spasticity in Japanese Subjects (1287)

Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Lower Limb Spasticity in Japanese Subjects (1287)

Duration of Treatment Effect Using IncobotulinumtoxinA for Upper-limb Spasticity: A Post-hoc Analysis.

The efficacy and safety of incobotulinumtoxinA ≤400 U was demonstrated in subjects with post-stroke upper-limb spasticity in a randomized, double-blind Phase 3 study with an open-label extension (OLEX; EudraCT number 2005-003951-11, NCT00432666). We report a post-hoc analysis of the duration of the treatment effect. Subjects completing the placebo-controlled main period (single injection cycle with 12–20-week observation) entered the OLEX and received a maximum of five further treatments (maximum duration 69 weeks) with incobotulinumtoxinA ≤400 U at flexible intervals with a minimum duration of 12 weeks, based on clinical need. Intervals between two consecutive incobotulinumtoxinA injections, excluding treatment intervals prior to the end-of-study visit, were evaluated. Of 437 incobotulinumtoxinA treatment intervals, 415 received by 136 subjects were included in the post-hoc analysis. More than half (52.3%; 217/415) of all incobotulinumtoxinA reinjections were administered at Week ≥14, 31.1% (129/415) at Week ≥16, 19.0% (79/415) at Week ≥18, and 11.6% (48/415) at Week ≥20. The duration of effect may vary and can exceed 20 weeks or more, which was observed in at least one injection cycle in 29.4% (40/136) subjects over the course of their treatment. Data show that incobotulinumtoxinA retreatment for upper-limb spasticity may not be required at 12-week intervals and provides evidence for flexible treatment intervals beyond this time frame.

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.

Efficacy and safety of incobotulinumtoxinA in the treatment of lower-limb spasticity in adults: The pattern customized study design

Efficacy and safety of incobotulinumtoxinA in the treatment of lower-limb spasticity in adults: The pattern customized study design

Efficacy and safety of incobotulinumtoxinA in the treatment of lower-limb spasticity in Japanese patients

Efficacy and safety of incobotulinumtoxinA in the treatment of lower-limb spasticity in Japanese patients

Duration of treatment effect using incobotulinumtoxinA for upper-limb spasticity: A post hoc analysis

The efficacy and safety of incobotulinumtoxinA ≤400 U was demonstrated in subjects with post-stroke upper-limb spasticity in a randomized, double-blind Phase 3 study with an open-label extension (OLEX; EudraCT number 2005-003951-11, NCT00432666). We report a post-hoc analysis of the duration of the treatment effect. Subjects completing the placebo-controlled main period (single injection cycle with 12-20-week observation) entered the OLEX and received a maximum of five further treatments (maximum duration 69 weeks) with incobotulinumtoxinA ≤400 U at flexible intervals with a minimum duration of 12 weeks, based on clinical need. Intervals between two consecutive incobotulinumtoxinA injections, excluding treatment intervals prior to the end-of-study visit, were evaluated. Of 437 incobotulinumtoxinA treatment intervals, 415 received by 136 subjects were included in the post-hoc analysis. More than half (52.3%; 217/415) of all incobotulinumtoxinA reinjections were administered at Week ≥14, 31.1% (129/415) at Week ≥16, 19.0% (79/415) at Week ≥18, and 11.6% (48/415) at Week ≥20. The duration of effect may vary and can exceed 20 weeks or more, which was observed in at least one injection cycle in 29.4% (40/136) subjects over the course of their treatment. Data show that incobotulinumtoxinA retreatment for upper-limb spasticity may not be required at 12-week intervals and provides evidence for flexible treatment intervals beyond this time frame.

Safety of incobotulinumtoxinA in multipattern treatment of upper- and lower-limb spasticity in children/adolescents with cerebral palsy: Pooled analysis of 3 large phase 3 studies

Safety of incobotulinumtoxinA in multipattern treatment of upper- and lower-limb spasticity in children/adolescents with cerebral palsy: Pooled analysis of 3 large phase 3 studies

Efficacy and safety of incobotulinumtoxinA for upper- or combined upper- and lower-limb spasticity in children and adolescents with cerebral palsy: Results of the Phase 3 XARA study

Efficacy and safety of incobotulinumtoxinA for upper- or combined upper- and lower-limb spasticity in children and adolescents with cerebral palsy: Results of the Phase 3 XARA study

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.

Efficacy and safety of IncobotulinumtoxinA in the treatment of lower limb spasticity in Japanese subjects

Objective: To confirm the efficacy and safety of botulinum toxin type A (BoNT-A) treatment incobotulinumtoxinA (INCO; Xeomin®, Merz Pharmaceuticals GmbH) in Japanese subjects from study sites in Japan with post-stroke spasticity in the lower limb (LL), using the Modified Ashworth Scale (MAS) spasticity score for the plantar flexors.

Efficacy and safety of incobotulinumtoxinA in post-stroke upper-limb spasticity in Japanese subjects: results from a randomized, double-blind, placebo-controlled study (J-PURE)

BackgroundUpper-limb spasticity frequently occurs after stroke and there is a clinical need for more effective therapies. The Phase III J-PURE study assessed the efficacy and safety of incobotulinumtoxinA up to 400 U for post-stroke upper-limb spasticity in Japan.MethodsIn the 12-week main period (MP) of this double-blind, placebo-controlled study, Japanese subjects with upper-limb spasticity received one injection cycle of incobotulinumtoxinA 400 U, 250 U, or matching placebo. Eligible subjects enrolled in an open-label extension (OLEX) period of three injection cycles of incobotulinumtoxinA 400 U (32–40 weeks). The primary objective was to establish the efficacy of a single incobotulinumtoxinA injection using the Modified Ashworth Scale (MAS) wrist score. Secondary efficacy outcomes and safety were also assessed.ResultsAmong 100 treated subjects, AUCs for incobotulinumtoxinA 400 and 250 U were significantly different versus placebo (p = 0.0014 and p = 0.0031, respectively) for change from baseline in MAS wrist score to the end of the MP, with similar results from baseline to week 4. IncobotulinumtoxinA 400 U was superior versus placebo across other spasticity patterns and at most study visits. Improvements were maintained throughout the OLEX period. Disability Assessment Scale and Investigator’s Clinical Global Impression scores improved significantly for incobotulinumtoxinA 400 U versus placebo from baseline to week 4 (p = 0.0067 and p < 0.0001, respectively). IncobotulinumtoxinA was well tolerated up to 52 weeks, with no unexpected adverse events.ConclusionIncobotulinumtoxinA reduced (pathologically) increased muscle tone, improved functionality and was well tolerated in Japanese subjects with post-stroke upper-limb spasticity.

Safety of incobotulinumtoxinA in the treatment of facial lines: Results from a pooled analysis of randomized, prospective, controlled clinical studies

BACKGROUND The safety and efficacy of incobotulinumtoxinA in aesthetics has been established in multiple studies. Although individual studies have been reported, a combined assessment of incobotulinumtoxinA safety across studies is not available. OBJECTIVE To assess the frequency of adverse events (AEs) across prospective incobotulinumtoxinA studies in aesthetics. MATERIALS AND METHODS Safety data were assessed from 9 placebo-controlled or active-controlled single-dose studies on glabellar frown lines (GFL), crow's feet (CF), and upper facial lines (UFL). Analyses by treatment cycle included 4 repeat-dose studies on GFL and UFL. RESULTS One thousand three hundred seventy-seven subjects received incobotulinumtoxinA (GFL, n = 1,189; CF, n = 83; UFL, n = 105) in single-dose studies (placebo-controlled studies: incobotulinumtoxinA, n = 866; placebo, n = 395). Over 1,000 subjects received incobotulinumtoxinA in repeat-dose studies (GFL, n = 880; UFL, n = 290). In placebo-controlled single-dose studies, incidences of treatment-related AEs ranged from 5.4% (GFL) to 22.9% (UFL). The most frequent treatment-related AE in single-dose studies was headache (GFL, 4.8%; UFL, 11.4%). In repeat-dose studies, incidence of AEs was highest during cycle 1 (GFL, 8.9%; UFL, 17.2%) and decreased across treatment cycles. No serious treatment-related AEs were observed. CONCLUSION Results confirm the favorable safety and tolerability of incobotulinumtoxinA. The frequency of treatment-related AEs was low and may decrease with subsequent treatments.

Safety of incobotulinumtoxinA in adult spasticity: Results from a pooled analysis of randomized prospective clinical studies

Safety of incobotulinumtoxinA in adult spasticity: Results from a pooled analysis of randomized prospective clinical studies

Efficacy and safety of incobotulinumtoxinA in the treatment of upper facial lines: Results from a randomized, double-blind, placebo-controlled, phase 3 study

Efficacy and safety of incobotulinumtoxinA in the treatment of upper facial lines: Results from a randomized, double-blind, placebo-controlled, phase 3 study

Safety of incobotulinumtoxinA in the treatment of shoulder spasticity due to cerebral causes as part of upper-limb treatment

Safety of incobotulinumtoxinA in the treatment of shoulder spasticity due to cerebral causes as part of upper-limb treatment