In-vivo assessment of application of folinic acid and botulinum toxin A in cleft lip surgical defects.

INTRODUCTION: Folinic acid and botulinum toxin A have shown promising results in wound healing in different studies. This study aimed to compare the effects of these approaches on wound healing after simulating cleft lip surgery in rats. METHODS: In this experimental animal study, after creating lip defects, 30 rats were randomly divided into three groups and received normal saline (CTL), botulinum toxin A (BOT), and folinic acid (FOL). Biopsy from the skin wounds was performed after 14- and 28-days. These samples were stained with haematoxylin and eosin and Masson trichrome staining. Finally, each pathological parameter of wound healing was rated in this study. RESULTS: While the inflammatory response was not different among the study groups, fibroblast proliferation and collagen deposition were significantly higher in FOL group compared to BOT group. Moreover, both BOT and FOL facilitated epithelial healing and 14-day angiogenesis as compared with normal saline. CONCLUSIONS: Improved wound healing was observed using both botulinum toxin A and folinic acid in rat animal models. However, the application of botulinum toxin A caused less fibroblast proliferation and collagen deposition which can potentially lead to less scar formation, which can be particularly important in the aesthetic zone.

Botulinum Toxin Injection for the Treatment of Strabismus: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the available evidence comparing the effectiveness of extraocular muscle botulinum toxin type A (BTXA) injection with eye muscle surgery for restoring ocular alignment in children and adults with nonparalytic, nonrestrictive horizontal strabismus. METHODS: Literature searches in the PubMed Cochrane Library, and clinical trial databases with no date restrictions, but limited to articles published in English, were conducted last on January 10, 2021. The searches yielded 515 citations, 40 of which were reviewed in full text by the first author. Fourteen articles met the criteria for inclusion (randomized or nonrandomized comparative studies, or case series with a minimum 50 patients; evaluating extraocular muscle BTXA injection for initial or repeat treatment of horizontal, nonparalytic, nonrestrictive strabismus; with at least 6 months of follow-up) and were graded by a methodologist. RESULTS: The 14 included studies consisted of 2 randomized clinical trials, 3 nonrandomized comparative studies, and 9 case series. All 5 comparative studies were graded level II evidence, and the 9 case series were graded level III evidence. Successful motor outcomes after BTXA injection were relatively consistent across 4 of the 5 comparative studies at 60%, when adjustment was made for differential selection bias in 1 of the studies. In the 4 studies, successful motor outcomes after surgery ranged from 66% to 77% with a mean follow-up of 23 to 75 months, and the outcomes were not significantly different from those after BTXA injection. In the fifth level II study, success was significantly higher with BTXA injection than with surgery (94% vs. 72%). The level III BTXA case series demonstrated higher motor success rates of 87% to 89% when children were treated in 2 muscles at a time; rates were lower in adults treated with single-muscle BTXA injection. CONCLUSIONS: Extraocular muscle injection of BTXA achieves a high rate of successful motor alignment, comparable with that achieved after eye muscle surgery for nonparalytic, nonrestrictive horizontal strabismus. Good alignment may require multiple BTXA injections, and it is not yet clear whether sensory outcomes are equivalent for BTXA injections versus eye muscle surgery in young children.

Routine Office Assessment After OnabotulinumtoxinA Injection for Overactive Bladder Is Unnecessary to Detect Clinically Significant Voiding Dysfunction.

OBJECTIVE: This study aimed to determine if routine assessment of patients after onabotulinumtoxinA injections for overactive bladder is necessary to detect clinically significant voiding dysfunction. METHODS: This retrospective cross-sectional cohort study analyzed patients who underwent intravesical injection of onabotulinumtoxinA for overactive bladder during a 4-year period. Patients were included for analysis if they returned for an office follow-up visit within 1 month of administration. Baseline demographic data; procedural details; postvoid residual volumes; abnormal postprocedure voiding symptoms, including urinary frequency, pain, or inability to void; urinary tract infections; and initiation of intermittent self-catheterization were recorded. Descriptive statistics, point-biserial and Pearson correlation analyses were performed. RESULTS: Two hundred thirty-seven injections were included in our analysis. Fifteen encounters, from 13 patients, required the initiation of intermittent self-catheterization (6.3%). The median postvoid residual in those treated with intermittent self-catheterization was 300 mL (min, max: 200, 750 mL); all had received 100 units of onabotulinumtoxinA. The most common symptom among those requiring intermittent self-catheterization was urgency (n = 13; 87%), whereas 93% (n = 14) had at least 1 bothersome symptom. Correlation analyses showed a weak positive correlation with elevated postvoid residual volume and a history of prolapse repair (r = 0.269, P = 0.004), and prior pelvic surgery (r = 0.205, P = 0.029). CONCLUSIONS: Clinically relevant urinary retention that required intermittent self-catheterization after onabotulinumtoxinA injection for overactive bladder occurred in 6.3% of participants in this sample. The vast majority of patients who required intermittent self-catheterization described symptoms that they were able to self-identify.

Comparison of botulinum toxins for treatment of movement disorders: real-world utilization and cost analysis in a national Medicare population.

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) is the single largest payer for health care in the United States and the largest payer by spending globally. Medicare Part B, with more than 50 million beneficiaries, currently has no broad mechanisms in place for promoting cost-effective care of injectable drugs. OBJECTIVE: To conduct a real-world utilization and cost analysis comparing botulinum toxins in movement disorders. METHODS: The 2017 Medicare Provider Utilization and Payment Data: Physician and Other Supplier dataset from CMS was used for this claims level analysis. Neurologists, ophthalmologists, or physiatrists who injected predominantly for movement disorders (defined as blepharospasm, cervical dystonia, sialorrhea, and/or spasticity) were included along with their patients. Botulinum toxins with FDA indications spanning these 3 specialties were included. RESULTS: A total of 891 physicians (406 ophthalmologists, 338 neurologists, and 147 physiatrists) along with their 29,954 botulinum toxin (27,441 onabotulinumtoxinA and 2,513 incobotulinumtoxinA) patients were included in the analysis. The average total drug cost per patient per year (PPPY) was significantly lower for incobotulinumtoxinA versus onabotulinumtoxinA ($2,099 vs. $3,115; P < 0.001), for an average savings of 32.6%. Annual average out-of-pocket costs were also significantly less expensive for incobotulinumtoxinA versus onabotulinumtoxinA ($486 vs. $719; P < 0.001), for an average savings of 32.4%. Across 74,346 total injection visits, there was no significant difference in dosing between the agents, with an average dosing ratio of 0.94 incobotulinumtoxinA to 1.0 onabotulinumtoxinA. Injections PPPY were 2.42 for onabotulinumtoxinA and 2.29 for incobotulinumtoxinA. Average reported wastage was 64% higher for onabotulinumtoxinA than it was for incobotulinumtoxinA. A budget impact analysis estimated that increasing incobotulinumtoxinA use in the movement disorder space to attain an overall 20% botulinum toxin market share would save Medicare $32.9 million over a 3-year period versus current use. CONCLUSIONS: IncobotulinumtoxinA was shown to be a less costly alternative than onabotulinumtoxinA with similar dosing in real-world practice in this large national Medicare population. Policies to increase use of agents that promote cost-effective evidence-based care should be further explored and implemented for this fundamental federal payer. DISCLOSURES: This research received no external funding. Kazerooni was an employee of Merz Pharmaceuticals at the time of the analysis. Watanabe received no compensation or funding for this research project. Watanabe is a member of the National Academies of Sciences, Engineering, and Medicine Forum on Drug, Discovery, Development, and Translation. This information, content, and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by the U.S. government or the National Academies of Sciences, Engineering.

Cost of fremanezumab, erenumab, galcanezumab and onabotulinumtoxinA associated adverse events, for migraine prophylaxis in Spain.

Objective: To compare the cost of adverse events (AEs) associated with preventive treatment of migraine with fremanezumab, versus erenumab, galcanezumab, and onabotulinumtoxinA.Methods: A probabilistic modeling analysis was performed, using second-order Monte Carlo simulations, with 1,000 simulations, in patients with at least 4 days of migraine per month, from the perspective of the National Health System and a time horizon of 12 weeks. The frequency of AEs described in the clinical trials was analyzed with 12 weeks of treatment. Unit costs (€) of management of AEs were obtained from public health prices, expert panels, and published Spanish studies.Results: Fremanezumab would generate average savings of -€469 (95% CI -€303; -€674) versus erenumab, -€268 (95% CI -€171; -€391) versus galcanezumab, -€1,100 (95% CI -€704; -€1,608) or -€1,295 (95% CI -€835; -€1,893) versus onabotulinumtoxinA using real-life or clinical trial data, respectively.Conclusions: The different safety profile of treatment with fremanezumab, compared to erenumab, galcanezumab, and onabotulinumtoxinA, would generate savings in health-care resources in all the scenarios considered.

National Trends in Neuromodulation for Urinary Incontinence Among Insured Adult Women and Men, 2004-2013: The Urologic Diseases in America Project.

OBJECTIVE: To examine US trends in neuromodulation for urinary incontinence (UI) treatment from 2004 to 2013. METHODS: This study utilized 2 data sources: the Optum© de-identified Clinformatics® Data Mart Database for privately insured adults aged 18-64 years with a UI diagnosis (N≈40,000 women and men annually) and the Medicare 5% Sample for beneficiaries aged ≥65 years with a UI diagnosis (N≈65,000 women and men annually). We created annual cross-sectional cohorts and assessed prevalence of UI-related neuromodulation procedures among men and women separately from 2004 to 2013. Analyses were conducted overall and stratified by age, race/ethnicity, and geographic region. RESULTS: Nearly all neuromodulation procedures occurred in outpatient settings. Sacral neuromodulation (SNM) procedures for UI in both women and men grew steadily from 2004 to 2013, with more procedures performed in women than men. Among women with UI, SNM prevalence grew from 0.1%-0.2% in 2004 to 0.5%-0.6% in 2013. Posterior tibial nerve stimulation (PTNS) experienced growth from 2011 to 2013. Chemodenervation of the bladder with onabotulinumtoxinA (BTX) combined with other injectable procedures (including urethral bulking) remained stable over time. CONCLUSIONS: From 2004 to 2013, SNM procedures remained relatively uncommon but increased consistently. PTNS experienced growth starting in 2011 when PTNS-specific insurance claims became available. BTX trends remain unclear; future studies should assess it separately from other injectable procedures. Neuromodulation has a growing role in UI treatment, and ongoing trends will be important to examine.

Assessment of Botulinum Neurotoxin Injection for Dystonic Hand Tremor: A Randomized Clinical Trial.

Importance: There is an unmet need for safe and efficacious treatments for upper-extremity dystonic tremor (DT). To date, only uncontrolled retrospective case series have reported the effect of botulinum neurotoxin (BoNT) injections on upper-extremity DT. Objective: To assess the effect of BoNT injections on tremor in patients with upper-extremity DT. Design, Setting, and Participants: In this placebo-controlled, parallel-group randomized clinical trial, 30 adult patients with upper-extremity DT treated at a movement disorder clinic in a tertiary care university hospital were randomized in a 1:1 ratio to BoNT or saline injection, 0.9%, using a computer-generated randomization sequence. Randomization was masked using opaque envelopes. The participant, injector, outcome assessor, and statistician were blinded to the randomization. Participants were recruited between November 20, 2018, and December 12, 2019, and the last follow-up was completed in March 2020. Interventions: Participants received electromyographically guided intramuscular injections of BoNT or placebo into the tremulous muscles of the upper extremity. Injection patterns and doses were individualized according to tremor phenomenologic findings. Main Outcomes and Measures: The primary outcome was the total score on the Fahn-Tolosa-Marin Tremor Rating Scale 6 weeks after the intervention. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. All patients were offered open-label BoNT injections after 12 weeks and reassessed 6 weeks later. Results: A total of 48 adult patients with a diagnosis of brachial dystonia with DT were screened. Fifteen were ineligible and 3 refused consent; therefore, 30 patients (mean [SD] age, 46.0 [18.6] years; 26 [86.7%] male) were recruited, with 15 randomized to receive BoNT and 15 to receive placebo. In the intention-to-treat group, the Fahn-Tolosa-Marin Tremor Rating Scale total score was significantly lower in the BoNT group at 6 weeks (adjusted mean difference, -10.9; 95% CI, -15.4 to -6.5; P < .001) and 12 weeks (adjusted mean difference, -5.7; 95% CI, -11.0 to -0.5; P = .03). More participants in the BoNT group reported global improvement on the Global Impression of Change (PGIC) assessment (PGIC 1, 2, and 3: BoNT: 4 [26.7%], 6 [40.0%], and 5 [33.3%]; placebo: 5 [33.3%], 10 [66.7%], and 0, respectively; P = .047). Subjective hand weakness (BoNT: 6 [40.0%]; placebo: 4 [28.6%], P = .52) and dynamometer-assessed grip strength (mean difference, -0.2 log10[kgf/m2]2/Hz-Hz; 95% CI, -0.9 to 0.4 log10[kgf/m2]2/Hz-Hz; P = .45) were similar in both groups. Conclusions and Relevance: In this randomized clinical trial, botulinum neurotoxin injections were superior to placebo in reducing tremor severity in upper-extremity DT. An individualized approach to muscle selection and dosing was beneficial without unacceptable adverse effects. Trial Registration: Clinical Trials Registry of India (http://ctri.nic.in) Identifier: CTRI/2018/02/011721.

Cost-effectiveness of botulinum neurotoxin A versus surgery for drooling: a randomized clinical trial.

AIM: This study compared the cost-effectiveness of botulinum neurotoxin A (BoNT-A) injections with two-duct ligation of the submandibular glands as treatment for severe drooling after one treatment cycle. METHOD: The study was part of a larger, partly single-blinded, randomized clinical trial (trialregister.nl identifier NTR3537). Data were collected between 2012 and 2017. Evaluation was at 32 weeks after one treatment cycle. Fifty-seven patients with cerebral palsy or other neurological, non-progressive disorders and severe drooling classified as having a drooling frequency ≥3 or a drooling severity ≥2, in whom conservative treatment was deemed ineffective, were randomized to treatment by BoNT-A or two-duct ligation. An incremental cost-effectiveness ratio (ICER) was calculated using the success rates as the measure of benefit. Treatment success was defined as a decrease ≥50% from baseline to 32 weeks in the subjective visual analogue scale for the severity of drooling or the objective drooling quotient. RESULTS: Fifty-three patients were analysed (22 females, 31 males; mean age 11y, range 8-22y). Average costs for one treatment cycle, which included one BoNT-A injection, were €1929 (standard error 62) for BoNT-A and €3155 (standard error 99) for two-duct ligation. Treatment success was in favour of two-duct ligation (63% vs 27%; number needed to treat 3). The ICER was €34 per 1% gain in treatment success in favour of two-duct ligation versus BoNT-A. INTERPRETATION: The additional cost of two-duct ligation is to some extent offset by a larger treatment success rate compared with BoNT-A. WHAT THIS PAPER ADDS: Botulinum neurotoxin A (BoNT-A) is less expensive per percentage of success than two-duct ligation. The additional cost of two-duct ligation over BoNT-A is offset by greater treatment success.

Contemporary Patterns of Third-line Treatments for Privately Insured Individuals With Overactive Bladder in the United States.

OBJECTIVE: To evaluate utilization of third-line overactive bladder (OAB) treatments including percutaneous tibial nerve stimulation (PTNS), sacral nerve stimulation (SNS), and intradetrusor botulinum toxin A (BTX) among privately insured patients and examine factors associated with their use. MATERIALS AND METHODS: Using MarketScan claims (2015-2017), we identified patients who underwent third-line OAB treatments based on procedure codes. Factors of interest included location, age, health plan, among others. We fit multivariable logistic regression models to estimate associations between pertinent factors with receipt of PTNS and SNS relative to BTX and associations between provider type and practice location with each treatment modality. RESULTS: We identified 7383 patients (mean age 50.9) in our cohort. SNS was used most frequently (n = 3602, 48.8%), while PTNS was used least frequently (n = 955, 12.9%). PTNS patients were more likely to reside in metropolitan areas (vs BTX: OR 1.6, 95%CI 1.3-2.1; vs SNS: OR 2.2, 95%CI 1.7-2.8), be aged 55 years or older (vs BTX: 54% vs 47%, OR 1.6, 95%CI 1.2-2.1; vs SNS: 54% vs 45%, OR 1.6, 95%CI 1.2-2.0), and be covered under a health maintenance organization (vs BTX: 17% vs 10%; vs SNS: 17% vs 10%, P <.01). Urologists were most likely to perform SNS, and gynecologists were most likely to perform BTX. 91% of PTNS procedures were performed in office settings. CONCLUSION: Among patients receiving third-line OAB treatment, PTNS was used infrequently. PTNS utilization was concentrated within urban areas, and among older patients and those covered by cost-conscious health maintenance organizations.

Minimally Invasive Facial Cosmetic Procedures for the Millennial Aesthetic Patient.

Millennials, defined as the generation of individuals born between 1981 and 1996, have emerged as one of the leading patient demographics seeking minimally invasive cosmetic procedures. Worldwide, millennials are more likely to consider preventative treatments compared to any other age-group. The three most popular minimally invasive facial procedures in this demographic include botulinum toxin, dermal fillers (eg, hyaluronic acid, calcium hydroxylapatite, facial fat-fillers), and microdermabrasion. Given their impact on the expanding aesthetic medicine market and their favorable disposition towards cosmetic procedures, it is necessary for dermatologists and cosmetic providers to understand their motivations and perspectives. While some research studies have elicited the opinions of millennials on social issues, education, and technology, there is a paucity of literature on millennials' impressions, opinions, and perceptions of aesthetic procedures. As a generation that has been reshaping the culture of healthcare delivery and encouraging the innovation of products and procedures with their unique values and perspectives, accounting for their beliefs and fostering a better understanding of their experiences will promote an elevation in the quality of their care.

Cost effectiveness and impact on quality of life of abobotulinumtoxinA and onabotulinumtoxinA in the treatment of children with lower limb spasticity in Canada.

Background: Injectable botulinum neurotoxins are a mainstay of treatment for pediatric spasticity. AbobotulinumtoxinA and onabotulinumtoxinA are both injectable toxin therapies used to treat pediatric lower limb (PLL) spasticity in Canada. The objective of this study was to assess the cost-effectiveness of abobotulinumtoxinA vs. onabotulinumtoxinA in the treatment of PLL spasticity in Canada.Methods: A probabilistic Markov cohort model with a 2-year time horizon was developed, with health states defined by response to therapy, as characterized by the goal attainment scale (GAS). Based on randomized controlled trial evidence, response to therapy was similar or higher for abobotulinumtoxinA relative to onabotulinumtoxinA; uncertainty was incorporated into model parameters, however, as the two therapies have not been compared head-to-head. Canadian resource use and cost data were incorporated.Results: In the base case, abobotulinumtoxinA generated 1.48 quality-adjusted life years over the model time horizon, compared to 1.47 for onabotulinumtoxinA. AbobotulinumtoxinA was associated with cost savings of $123 CAD, reflecting lower costs in both medication acquisition and health services. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for abobotulinumtoxinA over onabotulinumtoxinA. This dominant result persisted across probabilistic and scenario analyses.Key points for decision makersBased on a review of available clinical evidence, abobotulinumtoxinA was found to have significant and/or numerical efficacy benefits to onabotulinumtoxinA on functional outcomes (Goal Attainment Scale) and tone (Modified Ashworth Scale) and in the treatment of pediatric lower limb spasticityIn this cost-effectiveness analysis, abobotulinumtoxinA was found to be associated with greater quality-adjusted life years and lower costs than onabotulinumtoxinA (economically dominant)A limitation of this analysis was the uncertainty around key parameters. Specifically, the lack of head-to-head comparison data for the two therapies, and variable data regarding likely onabotulinumtoxinA dosing in PLL in clinical practice. However, across a range of plausible scenarios, the economic dominant result remained.

Long-term treatment of blepharospasm with botulinum toxin A: a service-based study over a 16-year follow-up in southern China.

OBJECTIVE: To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored. METHODS: We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group. RESULTS: The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05). CONCLUSION: The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.

Demographics of Men and Minorities in Cosmetic Clinical Trials of Botulinum Toxin and Hyaluronic Acid Fillers.

BACKGROUND: The demographics of men and minorities in clinical studies of nonsurgical cosmetic procedures have not been well described. There is a growing interest in nonsurgical cosmetic procedures. The patients studied in clinical trials may not be reflective of the real-world demographic of patients seeking nonsurgical cosmetic procedures. OBJECTIVE: To examine the demographics of men and minorities in clinical studies of nonsurgical cosmetic procedures. METHODS: A systematic review of clinical trials of botulinum toxin A (BTX-A) for facial rhytides and hyaluronic acid (HA) injectable fillers for soft-tissue augmentation was performed. Data on ethnicity and sex were collected and examined. RESULTS: Nineteen randomized controlled trials (RCTs) on BTX-A and 22 RCTs on HA were included for analysis. Men represented 11.8% of all participants. Men were more represented in the BTX-A RCTs (13.9%) compared with the HA RCTs (6.4%). Caucasian patients represented 67.1% of the total patients. Asian, Hispanic, and black patients represented 16.8%, 6.5%, and 5.4% of study participants, respectively. CONCLUSION: The proportion of men in clinical trials of BTX-A and HA reflects the real-world demographics of men undergoing these procedures. Hispanic and black patients were underrepresented in clinical trials.

Cost-Effectiveness of Sacral Neuromodulation versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: Results of the ROSETTA Randomized Trial.

PURPOSE: Sacral neuromodulation and intradetrusor onabotulinumtoxinA injection are therapies for refractory urgency urinary incontinence. Sacral neuromodulation involves surgical implantation of a device that can last 4 to 6 years while onabotulinumtoxinA therapy involves serial office injections. We assessed the cost-effectiveness of 2-stage implantation sacral neuromodulation vs 200 units onabotulinumtoxinA for the treatment of urgency urinary incontinence. MATERIALS AND METHODS: Prospective economic evaluation was performed concurrent with the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation vs. BoTulinum Toxin Assessment) randomized trial of 386 women with 6 or more urgency urinary incontinence episodes on a 3-day diary. Analysis is from the health care system perspective with primary within-trial analysis for 2 years and secondary 5-year decision analysis. Costs are in 2018 U.S. dollars. Effectiveness was measured in quality adjusted life-years (QALYs) and reductions in urgency urinary incontinence episodes per day. We generated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS: Two-year costs were higher for sacral neuromodulation than for onabotulinumtoxinA ($35,680 [95% CI 33,920-37,440] vs $7,460 [95% CI 5,780-9,150], p <0.01), persisting through 5 years ($36,550 [95% CI 34,787-38,309] vs $12,020 [95% CI 10,330-13,700], p <0.01). At 2 years there were no differences in mean reduction in urgency urinary incontinence episodes per day (-3.00 [95% CI -3.38 - -2.62] vs -3.12 [95% CI -3.48 - -2.76], p=0.66) or QALYs (1.39 [95% CI 1.34-1.44] vs 1.41 [95% CI 1.36-1.45], p=0.60). The probability that sacral neuromodulation is cost-effective relative to onabotulinumtoxinA is less than 0.025 for all willingness to pay values below $580,000 per QALY at 2 years and $204,000 per QALY at 5 years. CONCLUSIONS: Although both treatments were effective, the high cost of sacral neuromodulation is not good value for treating urgency urinary incontinence compared to 200 units onabotulinumtoxinA.

Cost-Effectiveness Analysis of Erenumab Versus OnabotulinumtoxinA for Patients with Chronic Migraine Attacks in Greece.

BACKGROUND: Migraine is a common, chronic neurovascular brain disorder with non-negligible multifaceted economic costs. Existing preventive treatments involve the selective use of onabotulinumtoxinA, which aims at migraine morbidity reduction for patients who have failed initial preventive treatment with oral agents. Erenumab is a new preventive treatment for migraines. OBJECTIVE: To evaluate the differences in costs and outcomes of the preventive treatment with erenumab versus onabotulinumtoxinA in patients with chronic migraines (CM) in Greece to assess the economic value of this treatment. METHODS: We conducted a cost-effectiveness analysis from both the payer and the societal perspective using a decision-tree analytic model. Outcomes were expressed in migraines avoided and in quality-adjusted life-years (QALYs). We obtained model inputs from the existing literature. The decision path adjusted for variation in the probability of adherence and the resulting differential effectiveness between the two treatments. Direct costs included the cost of the two drugs and administration costs, the costs of acute drugs used under usual care, and the costs of hospitalization, physician, and emergency department visits. Indirect costs for the societal perspective analyses included wages lost on workdays. The time-horizon of the analysis was 1 year and all costs were calculated in 2019 euros (€). Sensitivity analyses were conducted to control for parameter uncertainty and to evaluate the robustness of the findings. RESULTS: Our results indicate that treatment of CM with erenumab compared to onabotulinumtoxinA resulted in incremental cost-effectiveness ratios (ICERs) of €218,870 and €231,554 per QALY gained and €620 and €656 per migraine avoided, from the societal and the payer's perspective, respectively. Using a common cost-effectiveness threshold equal to three times the local gross domestic product (GDP) per capita (€49,000), for the erenumab ICERs to fall below this threshold, the erenumab price would have to be no more than €192 (societal perspective) or €173 (payer perspective). CONCLUSION: The prophylactic treatment of CM with erenumab in Greece might be cost effective compared to the existing alternative of onabotulinumtoxinA from both the payer and the societal perspective, but only at a highly discounted price. Nevertheless, erenumab could be considered a therapeutic option for patients who fail treatment with onabotulinumtoxinA.

Clinical Assessment of 2 Licensed AbobotulinumtoxinA Injection Volumes for the Treatment of Glabellar Lines.

BACKGROUND: Two licensed reconstitution volumes may be used to achieve the recommended abobotulinumtoxinA (ABO) dose for glabellar line correction. OBJECTIVE: Comparison of efficacy, safety, and subject satisfaction concerning treatment of moderate to severe glabellar lines with 2 different ABO reconstitution volumes. MATERIALS AND METHODS: Phase IV, prospective, randomized, multicenter, subject- and evaluator-blinded study: 60 subjects received 1 ABO (50 units) treatment, administered as a 1.5- or 2.5-mL reconstitution. Primary objective was Day 30 improvements (≥1-point) in glabellar line severity. Onset of effect, duration, subject satisfaction, and treatment-related adverse events (AEs) were assessed. RESULTS: At Day 30, 90.0% and 86.7% of subjects achieved ≥1-point improvements with 1.5- and 2.5-mL reconstitutions, respectively. Median time to onset of effect was 48 hours after treatment. At 24 hours, 26.7% achieved ≥1-point improvements with the 2.5-mL reconstitution versus 6.7% with the 1.5-mL reconstitution. Maximum response was at Day 14, and >40% maintained efficacy through Day 120 in each group. High subject satisfaction was sustained throughout observation. Most AEs were mild. No serious AEs were reported. CONCLUSION: Both ABO reconstitutions were well tolerated and effective in correcting glabellar lines with no significant differences concerning efficacy or duration of effect. No serious AEs were reported.

Assessment of Skin Physiology Change and Safety After Intradermal Injections With Botulinum Toxin: A Randomized, Double-Blind, Placebo-Controlled, Split-Face Pilot Study in Rosacea Patients With Facial Erythema.

BACKGROUND: Botulinum toxin (BTX) has been used cosmetically with good clinical efficacy and tolerable safety. OBJECTIVE: This randomized, double-blind, split-face clinical study aimed to investigate the efficacy and safety of intradermal BTX in patients with rosacea. MATERIALS AND METHODS: Twenty-four participants were enrolled and randomly given intradermal injections of BTX and normal saline in both cheeks. Clinician Erythema Assessment (CEA) score, Global Aesthetic Improvement Scale (GAIS) score, skin hydration, transepidermal water loss (TEWL), melanin content, erythema index, elasticity, and sebum secretions were evaluated at baseline and 2, 4, 8, and 12 weeks. RESULTS: On the BTX-treated side, the CEA score significantly decreased and the GAIS score significantly increased. The erythema index decreased at Weeks 4 and 8. Skin elasticity was improved at Weeks 2 and 4 and skin hydration, at Weeks 2, 4, and 8. However, TEWL and sebum secretion did not show significant differences. CONCLUSION: Intradermal BTX injections reduced erythema and rejuvenated the skin effectively and safely in patients with rosacea.

Repeated injections of botulinum toxin-A for epiphora in lacrimal drainage disorders: qualitative and quantitative assessment.

PURPOSE: To report the outcome of repeated botulinum toxin-A (BTA) injections in the lacrimal glands in patients with epiphora. METHODS: We performed retrospective chart review of patients who were injected with 2.5 units of BTA in the lacrimal gland. Epiphora and tear production were assessed by the Munk score and Schirmer-1 test, respectively, pre-injection and at 1 and 3 months post injection. Regarding repeated injections, the effects of the first were compared to those of the second and third injections. RESULTS: Forty-six eyes of 35 patients had an average of 2.3 injections per eye (range, 1-6). The mean Munk score significantly decreased from 3.72 to 1.87 at 1 month (p < 0.001) and 2.21 at 3 months (p < 0.001) after injection. The mean Schirmer-1 score also significantly decreased from 15.35 mm to 10.52 mm at 1 month (p < 0.001) and 12.48 mm at 3 months (p < 0.001) after injection. The mean reduction rates of Munk and Schirmer-1 scores after the second (66.1% and 29.8%, respectively) and the third injections (56.1% and 23.3%, respectively) were not significantly different from those after the first injection (63.3% and 26.1%, respectively) (p > 0.05 for each comparison). There was a significant correlation between the difficulty in exposing the lacrimal gland for injection and the risk of complication (p = 0.017). CONCLUSION: BTA injection in the lacrimal gland showed favourable outcomes; repeated injections did not compromise efficacy. BTA injection can be safely repeated for epiphora, especially in patients whose lacrimal gland can be easily exposed.

Multidose Botulinum Toxin A for Intralaryngeal Injection: A Cost Analysis.

OBJECTIVES: Botulinum toxin A (BtxA) injection is the mainstay treatment for laryngeal dystonias. BtxA product labeling states that reconstituted toxin should be used within 4 hours on a single patient despite several studies that have demonstrated multidose BtxA to be safe and effective. Many insurance carriers mandate the use of an outside pharmacy which necessitates a single-use approach. This study compares the cost savings of multidose BtxA for laryngeal dystonia compared to single-use. STUDY DESIGN: This is a retrospective review and projected cost savings analysis. METHODS: Records and billing information were reviewed for patients receiving BtxA for intralaryngeal injection at a single laryngology division in 2015. Inclusion criteria included CPT 64617 or J0585; exclusion criteria included CPT 64616. The price of BtxA 100 unit vial for calculation was $670. RESULTS: A total of 142 patients were seen for intralaryngeal BtxA injection resulting in 337 visits over 1 year. The average BtxA dose per visit was 2.86 units with an average of 3.06 procedure visits per year. The calculated cost of BtxA treatment using a single vial approach was found to be $2,050 per patient per year. If billed instead for $7/unit with 5 units wastage charge per visit, the yearly per patient charge is $168. Single vial-use of BtxA injection thus represents a 1,118% price increase versus multidose use. When estimated for yearly prevalence of spasmodic dysphonia, multidose BtxA use would save almost $100 million annually. CONCLUSIONS: Multidose botulinum toxin A application utilizing per unit billing is significantly less expensive than per single-use vial billing and would save the health-care system significant amount of money without any sacrifice in safety or effectiveness.