Efficacy and safety of onabotulinumtoxinA for the treatment of overactive bladder in men and women: A pooled analysis.

BACKGROUND: This pooled analysis of randomized controlled studies investigated the safety and efficacy of onabotulinumtoxinA in male and female patients with overactive bladder (OAB). METHODS: Data were pooled from four similarly designed trials in North America and Europe. Adults with idiopathic OAB for ≥6 months inadequately managed by at least one anticholinergic were randomized 1:1 or 2:1 to receive onabotulinumtoxinA 100 U or matched placebo in Cycle 1 and could request open-label retreatment with onabotulinumtoxinA 100 U at ≥12 weeks. Efficacy outcomes at Week 12 included the primary endpoint of mean urinary incontinence (UI) episodes per day and other variables, such as the proportion of patients with ≥50% reduction in daily UI episodes. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs). Analyses by sex were descriptive. Males were further analyzed by benign prostatic hyperplasia (BPH) diagnosis status. RESULTS: In the pooled population (N = 1564), there were 194 males (12.4%) and 1370 females (87.6%). Mean number of baseline UI episodes per day was 4.9 in males and 5.5 in females. At Week 12, numerically greater mean reductions from baseline in number of daily UI episodes were observed with the onabotulinumtoxinA 100 U group (females: -3.0; males: -2.2) versus placebo (females: -1.1; males: -1.3). Achievement of ≥50% reduction in daily UI episodes was numerically greater with onabotulinumtoxinA 100 U (females: 64.8%; males: 61.2%) versus placebo (females: 30.6%; males: 44.8%), and numerically higher in males without BPH (onabotulinumtoxinA: 65.1%; placebo: 50.9%) versus with BPH (onabotulinumtoxinA: 54.3%; placebo: 36.6%). A total of 34.7% of males and 39.4% of females experienced at least one TEAE in the first 12 weeks during treatment Cycle 1. Urinary tract infection rate was 13.1% in females and 4.2% in males; incidence of hematuria was 6.8% in males and 1.1% in females. Incidence of urinary retention (defined as incomplete emptying, requiring catheterization) was 2.7% in females and 4.7% in males. CONCLUSION: OnabotulinumtoxinA 100 U was efficacious and well tolerated in men and women with OAB, including in males with and without BPH. No new safety findings were identified when data were analyzed by sex.

Temporary Delayed Hypersensitivity Reaction to Botulinum Toxin-A After COVID-19 Vaccination: A Case Series.

PURPOSE: The occurrence of a hypersensitivity reaction with the injection of botulinum toxin type A (BTX-A) in cosmetic use is a rare complication. We report the largest case series of temporary delayed hypersensitivity reaction (DHR) with BTX-A following COVID-19 vaccination and the first cases to incobotulinum toxin A (incoBTX-A). METHODS: A retrospective multicentric case series of patients who developed a DHR to BTX-A after COVID-19 vaccination. RESULTS: Twelve patients were treated with BTX-A injections for the management of facial rhytids. The age range was between 29 and 45 years. Ten (83.3%) were female. Ten (83.3%) patients received incoBTX-A, and two received onabotulinum toxin A (onaBTX-A). All patients had COVID-19 vaccination (mRNA vaccine) between 1 and 7 months before. Within an average time of 24 h after BTX-A injection, all patients developed progressive facial swelling and erythema that were more prominent at the injection points. Intradermal allergic tests to BTX-A were performed in six (50%) patients, and the results were all negative. Adequate clinical control was achieved with systemic corticosteroids and antihistamines. After 1 year with no further vaccination, a new BTX-A treatment (provocation test) was performed in all patients with no secondary effects. CONCLUSION: Previous COVID-19 vaccination and the absence of new adverse events with further BTX-A injections suggest a temporary DHR. Clinicians should be aware of the importance of immunization history and its potential post-vaccine immunogenic effects with BTX-A. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of botulinum toxin type A in patients with painful temporomandibular joint disorders: a systematic review and meta-analysis.

Objective: To assess the therapeutic efficacy of botulinum toxin type A (BTX-A) for managing myofascial pain related to temporomandibular disorders (TMDs). Methods: This study was conducted according to the PRISMA 2020 statement guidelines. The PubMed, Embase, and Cochrane Library databases were searched. Only randomized controlled trials were included. The primary outcome was a pain score on the visual analog scale, and the secondary outcomes were maximum mouth opening and adverse effects. The Cochrane risk of bias tool was used to assess risk bias. A meta-analysis of studies with the same interventions, controls, assessment methods, and follow-up durations was performed. Results: A total of 519 studies were retrieved, of which 20 randomized controlled trials were included in the qualitative analysis and six were included in the meta-analysis. The results showed that, compared with placebo, BTX-A injection was more effective at relieving myofascial pain, and its effect was similar to that of conventional methods. However, there was no difference in maximum mouth opening between the two groups. After the study assessment with the RoB 2.0 tool, six studies showed a low risk of bias, 13 studies showed some concerns regarding the reported results, and only one study showed a high risk of bias. Adverse effects of BTX-A injection were observed in four studies. Conclusions: In conclusion, BTX-A is effective at relieving pain in TMD patients but does not improve mouth opening. To minimize adverse effects, we recommend a low dose of BTX-A for TMD patients who do not experience complete pain relief from conservative treatments.

Treatment of masseter muscle hypertrophy with botulinum toxin type A injection: A review of adverse events.

BACKGROUND: The popularity of noninvasive botulinum toxin type A (BTX-A) injections for masseter muscle hypertrophy is increasing among Asian individuals with a square-shaped lower face. AIMS: This study aimed to analyze the adverse events (AEs) caused by BTX-A injections into the masseter muscle. PATIENTS/METHODS: This observational study retrospectively evaluated 46 250 patients who underwent BTX-A injections into the masseter muscle in 2022. The inclusion criteria were the diagnosis of an AE by the physician at the return visit and subsequent follow-up of progress (n = 223). The patients who were lost to follow-up (n = 40) were excluded from the study. RESULTS: Among the 223 patients with AEs, the most common AE was paradoxical bulging (88.3%, n = 197/223). The average period from treatment until confirmation of improvement was 159.6 ± 113.6 days (range 13-667 days) for all AEs, all of which were temporary. The period until improvement was 166.1 days in the intervention group (n = 122) and 151.9 days in the observation group (n = 101) (p = 0.24). As the period until improvement of AEs included the period until the patients visited the clinics and the improvements were confirmed by physicians, the actual period was likely to have been shorter. CONCLUSIONS: (1) All AEs were temporary. (2) All AEs improved within 22.2 months (within 5.3 ± 3.8 months on average). (3) There was no significant difference between the intervention and observation groups in the period until the improvement of AEs.

Sustained benefits of onabotulinumtoxinA treatment in chronic migraine: An analysis of the pooled Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) randomized controlled trials.

OBJECTIVE: To characterize the long-term (56-week) benefits of continuous onabotulinumtoxinA treatment response in individuals with chronic migraine (CM) who achieved reduction to <15 headache days/month with treatment. BACKGROUND: There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy. METHODS: The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24-week, randomized, double-blind, placebo-controlled phase and a 32-week open-label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double-blind phase (Weeks 21-24; any 12 consecutive weeks; Weeks 13-24) and the entire study (Weeks 53-56; any 12 consecutive weeks; any 4-week period). We assessed the long-term impact on mean monthly headache days and changes from baseline on the six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2.1). RESULTS: We analyzed 1384 participants with chronic migraine (double-blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open-label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56-week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13-24 of the double-blind phase, significantly more onabotulinumtoxinA-treated (386/688 [56.1%]) than placebo-treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25-56, 81.1% (558/688) at Weeks 53-56, and 79.4% (546/688) during any consecutive 12-week period. Mean changes from baseline on the HIT-6 and MSQv2.1 questionnaire surpassed within-group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA-treated participants who achieved <15 monthly headache days during Weeks 21-24 had a greater mean HIT-6 score reduction (-6.5 vs. -1.4) and greater mean MSQv2.1 Role-Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period. CONCLUSIONS: Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache-related disability and migraine-specific quality of life compared with those who remained at or above the 15-monthly headache days threshold. Sustained benefits observed over 56 weeks support long-term onabotulinumtoxinA use for the prevention of CM.

Application of botulinum toxin in the repair of a complex ventral hernia. / Aplicación de toxina botulínica en la reparación de una hernia ventral compleja.

INTRODUCTION: Preoperative application of botulinum toxin type A has demonstrated to be safe and effective in the closure of complex ventral hernias in adults. However, its use in pediatrics has been little documented. CASE REPORT: We present the case of a 22-month-old girl with a complex abdominal wall ventral hernia secondary to multiple neonatal laparotomies. In a first procedure, botulinum toxin was administered using an intramuscular approach at six sites of the muscle layers surrounding the defect, under general anesthesia and ultrasound control. 4 weeks later, an open hernia repair was conducted, without complications. DISCUSSION: Botulinum toxin at low doses could facilitate the surgical treatment of complex ventral incisional hernias in children. Even though it is important to adjust dosage and anatomical reference points according to hernia type and patient age and weight, further studies are required to optimize these variables.

INTRODUCCION: La aplicación preoperatoria de toxina botulínica A ha demostrado ser segura y efectiva en el cierre de hernias ventrales complejas en adultos. Sin embargo, se ha documentado poco su uso en pediatría. CASO CLINICO: Se presenta el caso de una niña de 22 meses con una hernia de pared abdominal ventral compleja secundaria a múltiples laparotomías neonatales. En una primera intervención se administró por vía intramuscular toxina botulínica en seis puntos de las capas musculares alrededor del defecto bajo anestesia general y control ecográfico. Cuatro semanas después, se realizó una reparación abierta de la hernia, sin complicaciones. COMENTARIOS: La toxina botulínica a dosis bajas podría facilitar el tratamiento quirúrgico de hernias incisionales ventrales complejas en niños. Es importante ajustar la dosis y los puntos de referencia anatómicos según el tipo de hernia, la edad y el peso del paciente, aunque se requieren más estudios para optimizar estas variables.

Botulinum Toxin Type A and Hyaluronic Acid Dermal Fillers in Dentistry: A Systematic Review of Clinical Application and Indications.

Background: Botulinum toxin type A (BoNT-A) and hyaluronic acid (HA) dermal fillers are increasingly utilized in dentistry for therapeutic and aesthetic purposes. However, a comprehensive synthesis of their clinical applications and indications in dentistry is lacking. This systematic review aimed to analyze the clinical application and indications of BoNT-A and HA dermal fillers in dentistry, providing insights into their efficacy, safety profiles, and limitations. Methods: A systematic search was conducted in PubMed/MEDLINE databases to identify relevant studies published between 2018 and 2024. Medical Subject Headings (MeSH) terms and keywords related to BoNT-A, HA dermal fillers, dentistry, clinical applications, and indications were used. Study selection criteria included randomized controlled trials (RCTs) and non-RCTs involving human participants of any age group. Data extraction and synthesis followed established guidelines, focusing on study characteristics, participant demographics, intervention details, outcome measures, and key findings related to BoNT-A and HA dermal fillers' clinical application in dentistry. Results: Systematic searches across electronic databases and grey literature identified 857 records, with an additional 73 from hand searches. After screening titles and abstracts, 542 records were excluded, leaving 374 full-text publications for evaluation. Ultimately, 12 RCTs and 13 non-RCTs were included. The systematic review encompassed diverse geographic locations: Brazil, Italy, Spain, Syria, India, Egypt, Korea, and the Netherlands, involving samples sizes ranging from 14 to 143 participants. The review synthesized findings on HA's efficacy in various areas, including bone repair, gingivitis management, temporomandibular joint disorders, postoperative swelling reduction, periodontal defect treatment, chin and check projection and lips augmentation. BoNT-A exhibited promising efficacy in managing orofacial pain conditions, gummy smile treatment and neuromodulation of the lower third muscles. Safety profiles varied among studies, with some reporting minimal adverse effects while others noted dose-related concerns. Conclusion: BoNT-A and HA dermal fillers offer a wide array of clinical applications in dentistry, ranging from therapeutic interventions to aesthetic enhancements. Despite promising efficacy, careful consideration and monitoring of safety outcomes are essential when integrating these interventions into clinical practice. Further research addressing methodological limitations and safety concerns is warranted to optimize their utilization and improve patient care in dentistry.

Gait analysis using three-dimensional motion and ground reaction force systems in patients with hemiplegia treated with botulinum toxin type A in ankle plantar flexors.

Objective: The efficacy of botulinum toxin type A (BoNT-A) injection on spasticity has usually been measured using the range of motion (ROM) of joints and Modified Ashworth Scale (MAS); however, they only evaluate muscle tone at rest. We objectively analyzed the gait of three patients with hemiplegia using three-dimensional motion analysis and ground reaction force (GRF) systems to evaluate muscle tone during gait. Materials and Methods: We measured passive ankle dorsiflexion ROM with knee extension and the MAS score for clinical evaluation, and gait speed, stride length, single-leg support phase during the gait cycle, joint angle, joint moment, and GRFs for kinematic evaluation before and one month after BoNT-A injection. Results: All patients showed an increase in ankle dorsiflexion ROM, improvement in MAS score, and increase in stride length. Case 1 showed an increase in gait speed, prolongation of the single-leg support phase, increase in hip extension angle and moment, and improvement in the vertical and anterior-posterior components of the GRFs. Case 2 showed an increase in gait speed, improvement in double knee action, increase in ankle plantar flexion moment, and improvement in propulsion in the progressive component of the GRFs. Case 3 exhibited a laterally directed force in the GRFs. Conclusion: We evaluated the effects of BoNT-A injections in three patients with hemiplegia using three-dimensional motion analysis and GRFs. The results of the gait analysis clarified the improvements and problems in hemiplegic gait and enabled objective explanations for patients.

Clinical benefit of botulinum toxin for treatment of persistent TMD-related myofascial pain: A randomized, placebo-controlled, cross-over trial.

BACKGROUND: Injections of botulinum toxin type A (BoNT-A) have been proposed as an additional treatment modality for patients suffering chronic temporomandibular disorder (TMD)-related myofascial pain (MFP). BoNT-A impairs muscle function, along with its analgesic effect, and a minimal effective dose should be used. The objective of this randomized placebo-controlled crossover study was to evaluate the clinical benefit of a moderate dose (50 U) of BoNT-A. METHODS: Sixty-six subjects were randomized into two groups, one which received BoNT-A first and a second which received a saline solution (SS) first. Follow-ups were performed 2, 11, and 16 weeks after the injections. Diagnostic criteria for temporomandibular disorders (DC/TMD) diagnostic algorithms were used to evaluate characteristic pain intensity (CPI) and pain-related disability based on the Graded Chronic Pain Scale (GCPS). Electromyographic and bite force were also evaluated. RESULTS: The within-group analysis showed a significant improvement in pain intensity and pain-related disability after BoNT-A (p < 0.001, p = 0.005, p = 0.011) and SS (p = 0.003, p = 0.005, p = 0.046) injections up to week 16. The between-group analysis of pain-related variables revealed no differences between groups at any time. Nonetheless, BoNT-A, but not SS, caused a significant decline in muscle performance. The number needed to treat (NNT) regarding a clinically significant pain reduction (≥30%) was 6.3, 57.0, and 19.0 at 2, 11, and 16-week follow-ups favoring BoNT-A. CONCLUSIONS: Injections of 50 U of BoNT-A might improve MFP symptoms, but the specific effect of the drug on pain compared to the placebo is not obvious.

Investigating the impact of botulinum toxin type a on the migration of normal human dermal fibroblasts: An in vitro wound healing assay.

BACKGROUND: Botulinum toxin A (BoNT-A) is widely utilized in the management of hypertrophic and keloid scars. One proposed mechanism for scar prevention involves the inhibition of fibroblast migration in scars by BoNT-A. However, the data regarding the effect of BoNT-A on the migration of normal human dermal fibroblasts (NHDF) is limited. OBJECTIVES: The aim of this study was to investigate the inhibitory effect of different types and dilutions of BoNT-A on the migration of NHDF. METHODS: In vitro scratch wound assay, NHDF cells were cultured, incubated, and subjected to scratching using a sterile tip. Subsequently, the scratched NHDF monolayer was treated with different types of BoNT-A, including onabotulinumtoxinA (ONA), incobotulinumtoxinA (INCO), prabotulinumtoxinA (PRABO), or letibotulinumtoxinA (LETI), at varying concentrations of 10, 20, 25, 40, 50, and 100 units/milliliter (U/mL). Additionally, abobotulinumtoxinA (ABO) was administered at concentrations of 33, 50, 66, 71, 100, 150, 300, and 500 U/mL. Normal saline solution (NSS) served as a negative control. The extent of NHDF migration was evaluated by comparing each dilution of BoNT-A with the controls using high-content imaging at the 48-h time point. Furthermore, the viability of the of NHDF was assessed. RESULTS: The concentrations of 25, 40, and 50 U/mL of ONA (p < 0.001) and 25 U/mL of LETI (p < 0.05) demonstrated significantly inhibited NHDF migration in comparison to the control group. Conversely, all dilutions of PRABO, INCO, and ABO exhibited comparable NHDF migration to that of the control group. Regarding NHDF viability, no significant decrease was observed across any of the BoNT-A types and dilutions. CONCLUSION: Different types and dilutions of BoNT-A demonstrated variable inhibitory effects on NHDF migration in vitro. The selection of BoNT-A formulation may significantly impact the clinical outcome of scar prevention related to fibroblast migration.

Exploring Variable Approaches in Complex Hernia Repair: A Comprehensive Literature Review.

Surgeons have long grappled with categorizing complex hernias, leading to varied interpretations and fluctuating incidence rates. Complex Abdominal Wall Reconstruction (CAWR) addresses repairs for large hernias, with defined factors including size, previous repairs, mesh placement, infections, and comorbidities. This review explores pivotal surgical techniques for complex hernia repair, starting with Preoperative Progressive Pneumoperitoneum (PPP) and progressing to innovative methods like Botulinum Toxin Type A. Mesh fixation, both open and laparoscopic, plays a crucial role, with synthetic and biological mesh options discussed. Hybrid techniques and the "sandwich" approach are proposed for intricate cases. Each technique presents advantages and limitations, emphasizing the ongoing quest for optimal outcomes.

Comparison of smile attractiveness in cases with gummy smile treated with botulinum toxin and maxillary impaction surgery: A retrospective study.

This study aimed to compare the smile's attractiveness in patients submitted to the treatment of gummy smiles with botulinum toxin or maxillary impaction surgery. The retrospective sample comprised 26 patients divided into two groups: Group 1 (BTX): 13 patients (12 females and 1 male) with a mean age of 28.06 years (s.d. = 6.09) and mean gingival exposure during smile of 5.18 mm (s.d. = 1.51) treated with botulinum toxin; Group 2 (SURGICAL): 13 patients (9 females and 4 males) with a mean age of 30.59 years (s.d. = 5.72) and mean gingival exposure during smile of 5.21 mm (s.d. = 1.55) treated with orthognathic maxillary impaction surgery. The group of evaluators comprised 317 participants, divided into 143 orthodontists (85 females and 58 males) with a mean age of 41.40 (s.d. = 9.30); 62 dentists (47 female and 15 male) with a mean age of 35.44 (s.d. = 10.44), and 112 lay people (74 female and 38 male) with a mean age of 46, 91 (s.d. = 10.11) in a questionnaire on Google Forms. Without knowing the therapy used, the evaluators assigned scores to the photographs of the posed smile taken before (T1) and after (T2) treatment. Intergroup comparison of smile attractiveness was performed using the t-independent, one-way ANOVA, and Tukey tests. There was a significant improvement in smile attractiveness with treatment in both groups; however, the improvement was significantly better in the surgical group than in the BTX group. Orthodontists rated smile attractiveness significantly higher than dentists and laypersons for the final phase of the BTX and surgical groups. There was a significant improvement in the smile attractiveness with botulinum toxin application and orthodontic-surgical treatment. However, orthognathic surgery promoted a greater improvement in smile attractiveness than the application of botulinum toxin.

Effect of ultrasound-guided injection of botulinum toxin type A into shoulder joint cavity on shoulder pain in poststroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem. METHODS: This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score. DISCUSSION: Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function. TRIAL REGISTRATION: Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 .

A Validation of the Equivalence of the Cell-Based Potency Assay Method with a Mouse LD50 Bioassay for the Potency Testing of OnabotulinumtoxinA.

(1) Background: At present, the only potency assay approved in China for the in-country testing of botulinum toxin type A for injection products is the mouse bioassay (MBA). The Chinese market for neurotoxin products is rapidly expanding, but MBAs are subject to high variability due to individual variations in mice, as well as variations in injection sites, in addition to the limited number of batches tested for one MBA. Compared with the mLD50 method, the cell-based potency assay (CBPA) developed for the potency testing of onabotulinumtoxinA (BOTOX) by AbbVie not only does not use any experimental animals but also allows for significant time and cost savings. Due to the significant benefits conferred by the replacement of the mLD50 assay with CBPA in China, the CBPA method has been transferred, validated, and cross-validated to demonstrate the equivalence of the two potency methods. (2) Methods: The differentiated SiMa cells were treated with both BOTOX samples and the reference standard, and the cleaved SNAP25197 in the cell lysates was quantified using Chemi-ECL ELISA. A 4-PL model was used for the data fit and sample relative potency calculation. The method accuracy, linearity, repeatability, and intermediate precision were determined within the range of 50% to 200% of the labeled claim. A statistical equivalence of the two potency methods (CBPA and mLD50) was initially demonstrated by comparing the AbbVie CBPA data with NIFDC mLD50 data on a total of 167 commercial BOTOX lots (85 50U lots and 82 100U lots). In addition, six lots of onabotulinumtoxinA (three 50U and three 100U) were re-tested as cross-validation by these two methods for equivalence. (3) Results: The overall assay's accuracy and intermediate precision were determined as 104% and 9.2%, and the slope, R-square, and Y-intercept for linearity were determined as 1.071, 0.998, and 0.036, respectively. The repeatability was determined as 6.9%. The range with the acceptable criteria of accuracy, linearity, and precision was demonstrated as 50% to 200% of the labeled claim. The 95% equivalence statistic test using margins [80%, 125%] indicates that CBPA and mLD50 methods are equivalent for both BOTOX strengths (i.e., 50U and 100U). The relative potency data from cross-validation were within the range of ≥80% to ≤120%. (4) Conclusions: The CBPA meets all acceptance criteria and is equivalent to mLD50. The replacement of mLD50 with CBPA is well justified in terms of ensuring safety and efficacy, as well as for animal benefits.

Botulinum toxin type A is a potential therapeutic drug for chronic orofacial pain.

BACKGROUND: Botulinum toxin type A (BTX-A), produced by the gram-positive anaerobic bacterium Clostridium botulinum, acts by cleaving synaptosome-associated protein-25 (SNAP-25), an essential component of the presynaptic neuronal membrane that is necessary for fusion with the membrane proteins of neurotransmitter-containing vesicles. Recent studies have highlighted the efficacy of BTX-A in treating chronic pain conditions, including lower back pain, chronic neck pain, neuropathic pain, and trigeminal neuralgia, particularly when patients are unresponsive to traditional painkillers. This review focuses on the analgesic effects of BTX-A in various chronic pain conditions, with a particular emphasis on the orofacial region. HIGHLIGHT: This review focuses on the mechanisms by which BTX-A induces analgesia in patients with inflammatory and temporomandibular joint pain. This review also highlights the fact that BTX-A can effectively manage neuropathic pain and trigeminal neuralgia, which are difficult-to-treat chronic pain conditions. Herein, we present a comprehensive assessment of the central analgesic effects of BTX-A and a discussion of its various applications in clinical dental practice. CONCLUSION: BTX-A is an approved treatment option for various chronic pain conditions. Although there is evidence of axonal transport of BTX-A from peripheral to central endings in motor neurons, the precise mechanism underlying its pain-modulating effects remains unclear. This review discusses the evidence supporting the effectiveness of BTX-A in controlling chronic pain conditions in the orofacial region. BTX-A is a promising therapeutic agent for treating pain conditions that do not respond to conventional analgesics.

The Effectiveness of Combining Botulinum Toxin Type A and Therapeutic Exercise in Treating Spasticity in a Patient with Complicated Stiff-Person Syndrome: A Case Report.

Stiff-person syndrome is rare and disabling autoimmune condition that most frequently affects women, with no real predisposition by race. Diagnosis is often arduous, which is why patients concomitantly suffer from anxiety and depression. To date, drug therapy is based on the use of benzodiazepines, barbiturates, and baclofen. Refractory cases are treated with intravenous immunoglobulin, plasmapheresis, B lymphocyte depletion with rituximab, and even the implantation of intrathecal baclofen devices. Botulinum toxin injection is frequently used, even if it still has an unclear role in the literature. Our case report aims to demonstrate the efficacy of a combined treatment of botulinum toxin and therapeutic exercise in a 65-year-old patient with biceps brachii muscle hypertonia and diffuse spasms of the axial musculature, using rating scales such as the Numeric Rating Scale (NRS) and Modified Ashworth Scale (MAS), joint range of motion (ROM) measurement, and muscle dynamic stiffness mensuration, which is performed by using the MyotonPro®. All the assessments were conducted at the first evaluation (T0), soon after the combined treatment with botulin toxin and therapeutic exercise (T1), three months (T2), six months (T3), and eight months after the botulinum toxin injection (T4). The patient demonstrated benefits for more than 6 months with no side effects. The combined therapy of botulinum toxin and therapeutic exercise had an excellent result in our patient.

Botulinum toxin therapy for isolated first dorsal interosseous muscle pain and hypertrophy: A case report.

Botulinum toxin (BTX) injection can be an effective treatment for persistent pain and functional impairment associated with hypertrophy of the first dorsal interosseous muscle. It offers a non-surgical and minimally invasive alternative for those who have failed conservative treatment, showcasing the therapeutic promise of BTX for addressing similar musculoskeletal conditions.

Botulinum toxin type A in treating early-stage patients with small-angle acute acquired comitant esotropia.

AIM: To investigate botulinum toxin A (BTXA) efficacy on small-angle (≤25Δ) acute acquired concomitant esotropia (AACE) in early-stage patients. METHODS: The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study. A total of 72 small-angle AACE patients received BTXA extraocular muscle injection. Patients were grouped by onset-to-treatment time (Group A: ≤6mo, Group B: >6mo). Deviation of esotropia, eye alignment and stereopsis were analyzed at the period of pre/post-injection (1wk, 1, 3, and 6mo). Orthophoria rate at 6mo (horizontal deviation <10Δ and binocular single vision) were considered as outcome index. RESULTS: There were no significant baseline differences (P>0.05) between two groups except onset-to-treatment time (2mo vs 11mo, P<0.001). Higher orthophoria rates were in Group A at last follow-up (94.74% vs 73.53%, P=0.013). Post-BTXA deviations of two groups at 1mo showed no difference (P>0.05); while in 3 and 6mo Group A was significantly smaller than group B (all P<0.001). No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A. In Group B, deviation at 3mo (near: 2Δ vs 0, P<0.001; distance: 4Δ vs 0, P<0.001) and 6mo (near: 6Δ vs 0, P<0.001; distance: 6Δ vs 0, P<0.001) was significant increased compared to deviation at 1wk after treatment. Group A showed better stereopsis recovery in last follow-up compared to Group B (80″ vs 200″, P=0.002). Both groups obtained improved stereopsis after treatment (Group A: 80″ vs 300″, P<0.001; Group B: 200″ vs 300″, P=0.037). CONCLUSION: BTXA is effective for AACE with small deviation (≤25Δ) in early stage. Delayed treatment (>6mo) may reduce BTXA efficacy. Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.

Exploring botulinum toxin's impact on masseter hypertrophy: a randomized, triple-blinded clinical trial.

The present study aimed to assess the effectiveness and functional adverse effects of a single and multiple injections of botulinum toxin A (BoNT-A) for masseter hypertrophy (MH). Twenty-six women complaining about lower third facial enlargement due to MH, received 75 U of BoNT-A (abobotulinum toxin) in each masseter muscles. After 3 months, patients were randomly assigned to receive a second treatment session of Saline Solution: (G1; n = 11) or BoNT-A: (G2; n = 12). Muscle thickness (ultrasound), electrical activity (electromyography; EMG), masticatory performance, and subjective perception of MH were evaluated. Follow-up was performed at 1, 3 and 6 months. Muscle thickness, EMG activity, and masticatory performance were analyzed using ANOVA two-way and Sidak test as post-hoc. Masticatory performance was analyzed by the Friedman's test and Mann-Whitney test. Regarding inter-groups comparisons, there was a significant decrease in the left masseter muscle thickness in the G2 group at the 6 month follow-up (p < 0.02). For EMG, significant differences were evident at the 6 month assessment, with higher masseter activity for G1 (p < 0.05). For masticatory performance, no significant differences were observed throughout the study (p > 0.05) and a higher improvement in subjective perception of MH was observed in the 1 month follow-up for G2 (p < 0.05). In conclusion, BoNT-A is effective for MH, however multiple injections cause functional adverse effects in masseter muscle.

Results of a study examining the use of onabotulinumtoxinA in pediatric patients with overactive bladder.

BACKGROUND: There is a lack of approved treatments for pediatric patients with overactive bladder (OAB) with inadequate response to anticholinergic therapy. OnabotulinumtoxinA 100U is approved to treat OAB in adults based on data from randomized, pivotal trials. OBJECTIVE: To investigate the efficacy and safety of onabotulinumtoxinA treatment of OAB in children aged 12-17 years who were not adequately managed with anticholinergics. STUDY DESIGN: In this multinational, multicenter, randomized, double-blind, parallel-group, multiple-dose study (NCT02097121), pediatric patients with OAB were randomized 1:1:1 to receive onabotulinumtoxinA 25U, 50U, or 100U (≤6 U/kg). Patients could request retreatment starting at week 12. The primary endpoint was change from baseline to week 12 after treatment 1 in daily frequency of daytime urinary incontinence (UI) episodes. Safety assessments evaluated treatment-emergent adverse events (TEAEs). RESULTS: Of 68 screened patients, 55 received ≥1 treatment. Mean age was 14 years; 85.5% of patients were female. At week 12 after treatment 1, least squares mean change from baseline in daily frequency of daytime UI episodes showed a numerically greater reduction in the 100U arm (-2.4) versus the 25U arm (-1.4; P = 0.38), with a significant within-group change from baseline in the 100U arm (P = 0.0027). Achievement of treatment response was significantly greater with onabotulinumtoxinA 100U vs 25U (Figure). Median time to request retreatment was ≥16 weeks in all groups. The most frequently reported TEAEs were nasopharyngitis (10.9%) and urinary tract infection (UTI; 10.9%). Urinary retention was observed in 1 patient during treatment cycle 2; there were no serious TEAEs of UTI or urinary retention. Throughout 2 additional treatment cycles continued efficacy for the 100U dose arm was observed along with a consistent safety profile. DISCUSSION: Change in daily frequency of UI episodes at week 12 in treatment cycle 1 was not significantly different between arms. However, ≥50% response rate was significantly higher with onabotulinumtoxinA 100U versus 25U. Enrollment challenges that lowered the sample size could have reduced statistical power. Also, the lack of a placebo arm and the observed benefit with the 25U comparator limited interpretation. CONCLUSIONS: OnabotulinumtoxinA injections were well tolerated in children with OAB at all doses studied. Although the primary endpoint was not met, the significantly greater treatment response rate observed with onabotulinumtoxinA 100U versus 25U suggests additional benefit of the higher dose, without additional safety concerns.