Cost Efficiency Analysis for Spasticity Management Based on Physician Botulinum Toxin Prescribing Habits.

OBJECTIVE: To estimate differences in botulinum toxin type A (BoNT-A) treatment costs per patient for spasticity-injecting physicians, with a focus on physicians' use of alternative BoNT-A agents other than onabotulinumtoxinA. DESIGN: Retrospective cohort study. SETTING: National Medicare data for fee-for-service beneficiaries in 2017. PARTICIPANTS: A total of 116 physicians, 6829 BoNT-A procedures, and 3051 patients were included in this analysis. Most physicians were physiatrists (84%) and used only onabotulinumtoxinA (82%). INTERVENTIONS: Type of BoNT-A selected by physicians was the independent variable of interest. Included physicians were separated into 2 groups: (1) onabotulinumtoxinA only injectors and (2) abobotulinumtoxinA and/or incobotulinumtoxinA injectors (may still use onabotulinumtoxinA). MAIN OUTCOME MEASURE: Average cost per patient per year. RESULTS: The total average BoNT-A cost per patient per year was significantly less for physicians who used abobotulinumtoxinA and/or incobotulinumtoxinA vs those who used only onabotulinumtoxinA ($3684 vs $4739; P=.01). Patients' average annual out-of-pocket costs also reflected a similar difference ($855 vs $1082; P=.02) between the groups. Doses used and numbers of injections per patient per year were not significantly different between groups. CONCLUSIONS: The present analysis demonstrated lower cost per patient for both the payer and patient when physicians used types of BoNT-A other than onabotulinumtoxinA for spasticity. Nevertheless, most physicians in this spasticity-focused study used exclusively onabotulinumtoxinA, the most expensive BoNT-A available. Reasons for this are complex and include history on the market and approved indications beyond those associated with spasticity. However, future research should continue to identify such issues with a goal of finding solutions to improve cost inefficiencies.

Cost-of-illness study for axillary hyperhidrosis in Japan.

The prevalence of primary axillary hyperhidrosis in Japan is 5.75% (males, 6.60%; females, 4.72%) in the population aged 5-64 years. No study on comprehensively evaluated direct medical costs, hygiene product costs, and productivity loss in axillary hyperhidrosis patients has been published in Japan. The aim of this study was to estimate the cost of illness for axillary hyperhidrosis in Japan by conducting a nationwide insurance claims database analysis and a cross-sectional Web-based survey. Among patients diagnosed with primary axillary hyperhidrosis at least once between November 2012 and October 2019, health insurance receipt data of 1447 patients were analyzed. A cross-sectional Web-based survey was conducted on 321 patients aged 16-59 years with axillary hyperhidrosis to calculate hygiene product costs and productivity loss using a Work Productivity and Activity Impairment questionnaire. Furthermore, nationwide estimation was performed for the hygiene product costs and productivity loss based on the number of patients estimated from the prevalence. The annual direct medical costs per axillary hyperhidrosis patient were ¥91 491 in 2016, ¥93 155 in 2017, and ¥75 036 in 2018. In all of these years, botulinum toxin type A injection accounted for approximately 90% of the total costs. The annual total cost of hygiene products per axillary hyperhidrosis patient was ¥9325. The overall work impairment (%) of working patients with axillary hyperhidrosis was 30.52%, and its monthly productivity loss was ¥120 593/patient. The activity impairment (%) of full-time housewives with axillary hyperhidrosis was 49.05% and its monthly productivity loss was ¥176 368/patient. The annual hygiene product cost based on the nationwide estimation was ¥24.5 billion and the monthly productivity loss was ¥312 billion. The significant cost associated with axillary hyperhidrosis was clarified. If out-of-pocket expenses for treatments not covered by health insurance are included in the estimation, the cost will further increase.

Cost-Effectiveness Analysis Between Sacral Neuromodulation and OnabotulinumtoxinA for the Treatment of Refractory Overactive Bladder in Women: A Systematic Review.

OBJECTIVE: We summarized the evidence evaluating the cost-effectiveness of sacral neuromodulation (SNM) versus onabotulinumtoxinA (BONT/A) in the treatment of refractory overactive bladder (OAB) among women. METHODS: We searched PubMed Medline (1946-2019), EMBASE (1947-2019), Web of Science (1900-2019), Clinical Trials.gov, reviewed references of included studies, and Cochrane subsets of CDSR, DARE, CENTRAL, and NHSEED. We included cost-utility and cost-effectiveness analyses or decision analysis comparing SNM versus BONT/A in women with nonneurogenic refractory OAB. Primary outcomes included incremental cost-effectiveness ratios (ICERs), reported as cost per quality-adjusted life year (QALY), which were abstracted or calculated. RESULTS: Five studies met the inclusion criteria. Three studies were industry supported. Two studies of high quality found BONT/A to be dominant over SNM (ICER range of $415,571/QALY at 5 years and $236,370/QALY at 10 years). This trend was further supported by a third study of high quality that favored BONT/A because SNM was not cost-effective (ICER, $116,427/QALY at 2 years). In contrast, 2 other studies of lower quality found that SNM was cost-effective or dominant in comparison to BONT/A (ICER range, $3,717/QALY to €15,226/QALY at 10 years). In general, models were sensitive to treatment duration, intervention setting, and lacked robust data on long-term outcomes. CONCLUSIONS: OnabotulinumtoxinA is more cost-effective for managing refractory OAB when compared with SNM. However, it remains unclear whether this finding holds true long term for what is considered a lifelong condition.

Effectiveness of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization as migraine prevention in the United States.

BACKGROUND: Migraine is a common neurological disease that can have a substantial impact on patients' lives and on society. Erenumab, a fully human monoclonal antibody that targets the calcitonin gene-related peptide receptor, was specifically developed for migraine prevention. The efficacy of erenumab has been established in several clinical trials; however, the real-world comparative effectiveness of erenumab has not been fully investigated. OBJECTIVE: To evaluate the real-world impact of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization (HCRU) among patients with migraine in the United States. METHODS: This retrospective US claims analysis (Optum's deidentified Clinformatics Data Mart Database) evaluated patients aged at least 18 years diagnosed with migraine who initiated erenumab or onabotulinumtoxinA between May 1, 2018, and September 30, 2019 (index date: first erenumab/onabotulinumtoxinA claim). Cohorts were matched 1:1 using the propensity score (PS) method (greedy match with caliper = 0.1). Stratification was performed based on gender, chronic migraine without aura diagnosis, onabotulinumtoxinA use, and acute/preventive drug use. The impact of erenumab and onabotulinumtoxinA on acute medication usage and HCRU was assessed in the 6-month post-index period. An exploratory analysis assessed the impact of erenumab and onabotulinumtoxinA on a composite endpoint of: (1) outpatient visit with a migraine diagnosis and associated acute medication claim, (2) hospital admission with a primary migraine diagnosis, or (3) emergency department visit with a primary migraine diagnosis. PS-matched data were used for comparative analyses; logistic regression with covariate adjustment was used for dichotomous variables, and a negative binomial model was used for count variables, with odds ratios or rate ratios (RRs) and 95% CIs calculated. RESULTS: Following stratified PS matching, 1,338 patients were included in both cohorts. At 6 months, the adjusted average number of claims per person for any acute medication was significantly lower in the erenumab cohort (1.13 vs 1.29 in the onabotulinumtoxinA cohort; RR = 0.88; 95% CI = 0.80-0.96; P = 0.0069), although the difference in the number of claims for triptans and barbiturates was statistically nonsignificant. The adjusted average number of all-cause and migraine-specific visits per person to health care providers was generally lower in the erenumab cohort compared with the onabotulinumtoxinA cohort. Patients in the erenumab cohort had a significantly lower number of composite events (0.44 vs 0.69 in the onabotulinumtoxinA cohort; RR = 0.63; 95% CI = 0.56-0.71; P < 0.0001). Similarly, the adjusted proportion of patients with any of the 3 composite events was lower in the erenumab cohort (31.7% vs 44.3% in the onabotulinumtoxinA cohort; OR = 0.59; 95% CI = 0.49-0.70; P < 0.0001). CONCLUSIONS: In this retrospective claims analysis study, erenumab significantly reduced acute medication usage (opioids and nonsteroidal anti-inflammatory drugs; any acute medication when analyzed together) and HCRU to a greater extent than onabotulinumtoxinA. DISCLOSURES: This study was supported by Novartis Pharma AG. Novartis employees contributed to the study design, analysis of the data, and the decision to publish the results. Fang, Abdrabboh, Glassberg, Vo, and Ferraris are employed by Novartis. Zhou and Shen are employed by KMK Consulting, Inc., which received funding from Novartis to conduct the study. Tepper reports grants from Allergan, Amgen, ElectroCore, Eli Lilly, Lundbeck, Neurolief, Novartis, Satsuma, and Zosano, outside the submitted work; personal fees from Dartmouth-Hitchcock Medical Center, American Headache Society, Thomas Jefferson University, Aeon, Align Strategies, Allergan/AbbVie, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, ClearView Healthcare Partners, CoolTech, CRG, Currax, Decision Resources, DeepBench, DRG, Eli Lilly, Equinox, ExpertConnect, GLG, Guidepoint Global Healthcare Consultancy Group, Health Science Communications, HMP Communications, Impel, InteractiveForums, M3 Global Research, Magellan Rx Management, Medicxi, Navigant Consulting, Neurorelief, Nordic BioTech, Novartis, Pulmatrix, Reckner Healthcare, Relevale, SAI MedPartners, Satsuma, Slingshot Insights, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, System Analytic, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano, Krog and Partners, and Lundbeck, outside the submitted work; and CME honoraria from American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute PeerView, Medical Education Speakers Network, Miller Medical Communications, North American Center for CME, Physicians' Education Resource, Rockpointe, ScientiaCME, WebMD/Medscape. The abstract and poster of these results were presented at The Migraine Trust Virtual Symposium (MTIS), October 3-9, 2020.

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.

Cost Effectiveness of Sacral Neuromodulation and OnabotulinumtoxinA in Managing Refractory Idiopathic Overactive Bladder.

Little information from clinical and modelled studies are available on cost effectiveness of OnabotulinumtoxinA and SNM for the treatment of idiopathic overactive bladder. We aimed to summarize the evidence in this regard from different healthcare systems. Seven studies from 5 countries were reviewed. Some modelled studies with a 10-year time frame showed that sacral neuromodulation became dominant long-term; others suggested OnabotulinumtoxinA was more cost effective at <5 years. There was considerable heterogeneity in the base case/sensitivity analysis and statistical modelling among the studies. Clinical studies with longer term follow-up will help determine cost effectiveness more accurately.

National Patterns of Filled Prescriptions and Third-Line Treatment Utilization for Privately Insured Women With Overactive Bladder.

OBJECTIVE: The aim of this study was to evaluate national patterns of care for women with overactive bladder (OAB) in an administrative data set and identify potential areas for improvement. METHODS: We performed an analysis using the OptumLabs Data Warehouse, which contains deidentified administrative claims data from a large national US health insurance plan. The study included women, older than 18 years, with a new OAB diagnosis from January 1, 2007, to June 30, 2017. We excluded those with an underlying neurologic etiology, with interstitial cystitis/painful bladder syndrome, were pregnant, or did not have continuous enrollment for 12 months before and after OAB diagnosis. Trends in management were assessed via the Cochran-Armitage test. Time to discontinuation among medications was compared using t test. RESULTS: Of 1.4 million women in the database during the study time frame, 60,246 (4%) were included in the study. Median age was 61 years [interquartile range (IQR), 50-73], and median follow-up was 2.6 years (IQR, 1.6-4.2). Overall, 37% were treated with anticholinergics, 5% with beta-3 agonists, 7% with topical estrogen, and 2% with pelvic floor physical therapy; 26% saw a specialist; and 2% underwent third-line therapy. Median time to cessation of prescription filling was longer for beta-3 agonists versus anticholinergics [median, 4.1 months (IQR, 1-15) vs 3.6 months (IQR, 1-10); P < 0.0001]. Use of third-line therapies significantly increased over the study time frame, from 1.1% to 2.2% (P < 0.0001). CONCLUSIONS: Most of the patients do not continue filling prescriptions for OAB medications, and a minority of patients were referred for specialty evaluation. Although third-line therapy use is increasing, it is used in a small proportion of women with OAB. Given these patterns, there may be underutilization of specialist referral and other OAB therapies.

Treatment patterns and costs among patients with OAB treated with combination oral therapy, sacral nerve stimulation, percutaneous tibial nerve stimulation, or onabotulinumtoxinA in the United States.

INTRODUCTION: Treatment patterns and costs were characterized among patients with overactive bladder (OAB) receiving later-line target therapies (combination mirabegron/antimuscarinic, sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], or onabotulinumtoxinA). METHODS: In a retrospective cohort study using 2013 to 2017 MarketScan databases, two partially overlapping cohorts of adults with OAB ("IPT cohort": patients with incident OAB pharmacotherapy use; "ITT cohort," incident target therapy) with continuous enrollment were identified; first use was index. Demographic characteristics, treatment patterns and costs over the 24-month follow-up period were summarized. Crude mean (standard deviation [SD]) OAB-specific (assessed by OAB diagnostic code or pharmaceutical dispensation record) costs were estimated according to target therapy. RESULTS: The IPT cohort comprised 54 066 individuals (mean [SD] age 58.5 [15.0] years; 76% female), the ITT cohort, 1662 individuals (mean [SD] age 62.8 [14.9] years; 83% female). Seventeen percent of the IPT cohort were treated with subsequent line(s) of therapy after index therapy; among those, 73% received antimuscarinics, 23% mirabegron, and 1.4% a target therapy. For the ITT cohort, 32% were initially treated with SNS, 27% with onabotulinumtoxinA, 26% with combination mirabegron/antimuscarinic, and 15% with PTNS. Subsequently, one-third of this cohort received additional therapies. Mean (SD) costs were lowest among patients receiving index therapy PTNS ($6959 [$7533]) and highest for SNS ($29 702 [$26 802]). CONCLUSIONS: Costs for SNS over 24 months are substantially higher than other treatments. A treatment patterns analysis indicates that oral therapies predominate; first-line combination therapy is common in the ITT cohort and uptake of oral therapy after procedural options is substantial.

Economic consequences of migraine in Sweden and implications for the cost-effectiveness of onabotulinumtoxinA (Botox) for chronic migraine in Sweden and Norway.

BACKGROUND: Migraine is a common and incapacitating condition, with severe impact on the quality of life (QoL) of the afflicted and their families, and negative economic consequences through decreased workforce participation, reduced functional ability and elevated healthcare costs. This study aimed to describe the economic consequences of migraine in Sweden using cost of illness survey data and, based on this data, assess the cost-effectiveness of onabotulinumtoxinA (Botox) for the treatment of chronic migraine in Sweden and Norway. METHODS: A survey study was conducted in Swedish migraine patients, with questions on patient characteristics, headache frequency and severity, effect on daily activities and work, QoL, health resource utilization, and medication use. Resulting costs were estimated as annual averages over subgroups of average monthly headache days. Some results were used to inform a Markov cost-effectiveness chronic migraine model. The model was adapted to Sweden and Norway using local data. The analysis perspective was semi-societal. Results' robustness was tested using one-way, structural, and probabilistic sensitivity analyses. RESULTS: Results from the cost of illness analysis (n = 454) indicated a clear correlation between decreased QoL and increased costs with increasing monthly headache days. Total annual costs ranged from EUR 6221 in patients with 0-4 headache days per month, to EUR 57,832 in patients with 25-31. Indirect costs made up the majority of costs, ranging from 82% of total costs in the 0-4 headache days group, to 91% in 25-31 headache days. The cost-effectiveness analyses indicated that in Sweden, Botox was associated with 0.223 additional QALYs at an additional cost of EUR 4126 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of EUR 18,506. In Norway, Botox was associated with 0.216 additional QALYs at an additional cost of EUR 4301 compared to placebo, resulting in an ICER of EUR 19,954. CONCLUSIONS: In people with migraine, an increase in monthly headache days is clearly related to lower QoL and higher costs, indicating considerable potential costs-savings in reducing the number of headache days. The main cost driver for migraine is indirect costs. Botox reduces headache days and is a cost-effective treatment for chronic migraine in Sweden and Norway.

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.

Protocol for the economic evaluation of the InTENSE program for rehabilitation of chronic upper limb spasticity.

BACKGROUND: Assessment of the costs of care associated with chronic upper-limb spasticity following stroke in Australia and the potential benefits of adding intensive upper limb rehabilitation to botulinum toxin-A are key objectives of the InTENSE randomised controlled trial. METHODS: Recruitment for the trial has been completed. A total of 139 participants from 6 stroke units across 3 Australian states are participating in the trial. A cost utility analysis will be undertaken to compare resource use and costs over 12 months with health-related quality of life outcomes associated with the intervention relative to a usual care comparator. A cost effectiveness analysis with the main clinical measure of outcome, Goal Attainment Scaling, will also be undertaken. The primary outcome measure for the cost utility analysis will be the incremental cost effectiveness ratio (ICER) generated from the incremental cost of the intervention as compared to the incremental benefit, as measured in quality adjusted life years (QALYs) gained. The utility scores generated from the EQ-5D three level instrument (EQ-5D-3 L) measured at baseline, 3 months and 12 months will be utilised to calculate the incremental Quality Adjusted Life Year (QALY) gains for the intervention relative to usual care using area-under the curve methods. DISCUSSION: The results of the economic evaluation will provide evidence of the total costs of care for patients with chronic upper limb spasticity following stroke. It will also provide evidence for the cost-effectiveness of adding evidence-based movement therapy to botulinum toxin-A as a treatment, providing important information for health system decision makers tasked with the planning and provision of services.

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.

Cost-Effectiveness of Long-Term, Targeted OnabotulinumtoxinA versus Peripheral Trigger Site Deactivation Surgery for the Treatment of Refractory Migraine Headaches.

BACKGROUND: Chronic migraines affect approximately 2 percent of the U.S. population and cost an estimated $17 billion per year. OnabotulinumtoxinA (botulinum toxin type A) is a U.S. Food and Drug Administration-approved prophylactic medication for chronic migraine headaches and is best injected in a targeted fashion into specific trigger sites. The purpose of this study was to determine the cost-effectiveness of long-term, targeted botulinum toxin type A versus peripheral trigger site deactivation surgery for the treatment of migraine headaches. METHODS: A Markov model was constructed to examine long-term, targeted botulinum toxin type A versus peripheral trigger site deactivation surgery. Costs, utilities, and other model inputs were identified from the literature. One-way and probabilistic sensitivity analyses were performed. An incremental cost-effectiveness ratio under $50,000 per quality-adjusted life-year was considered cost-effective. RESULTS: The mean cost of peripheral trigger site deactivation surgery was $10,303, with an effectiveness of 7.06; whereas the mean cost of long-term, targeted botulinum toxin type A was $36,071, with an effectiveness of 6.34. Trigger-site deactivation surgery is more effective and less costly over the time horizon of the model. One-way sensitivity analysis revealed that surgery is the most cost-effective treatment in patients requiring treatment for greater than 6.75 years. CONCLUSIONS: Based on this model, peripheral trigger site deactivation surgery is the more cost-effective option for treating refractory migraine headaches requiring treatment beyond 6.75 years. The model reveals that peripheral trigger-site deactivation surgery is more effective and less costly than long-term, targeted botulinum toxin type A over the course of a patient's lifetime.

Real World Performance of Sacral Neuromodulation and OnabotulinumtoxinA for Overactive Bladder: Focus on Safety and Cost.

PURPOSE: We aimed to determine the real world safety and cost of third line overactive bladder therapies, including onabotulinumtoxinA and sacral neuromodulation. MATERIALS AND METHODS: We performed an all-inclusive, population based cohort study of third line therapies of overactive bladder (sacral neuromodulation or onabotulinumtoxinA) using the statewide surgical data captured in the New York Statewide Planning and Research Cooperative System. The main outcome measures were 30-day safety events, and 1 and 3-year health care utilization costs. Propensity score matching was done to control for confounding factors and comparative analyses of safety events were also performed. RESULTS: Our cohort included 2,680 patients, of whom 1,328 underwent sacral neuromodulation and 1,352 received onabotulinumtoxinA from January 1, 2013 through December 31, 2016. Average ± SD age was 61.7 ± 16.3 years and 82.7% of the patients were female. Sacral neuromodulation implantation led to re-intervention in 15.8% of cases within 1 year and in 26.1% at 3 years. In this comparative analysis patients who received onabotulinumtoxinA therapy were at higher risk for urinary tract infection, hematuria, urinary retention and an emergency room visit compared to those treated with sacral neuromodulation. The overall cost of onabotulinumtoxinA was lower than the cost of the sacral neuromodulation device (cost at 1 year $2,896 vs $15,343 and at 3 years $3,454 vs $16,189, each p <0.01). CONCLUSIONS: Sacral neuromodulation implantation was more expensive than onabotulinumtoxinA injection. However, patients who underwent sacral neuromodulation had a lower complication rate than patients treated with onabotulinumtoxinA. A quality improvement collective database must be created to track information on onabotulinumtoxinA and sacral neuromodulation treatment. This would help generate better performance and comparative data for patient and physician decision making.

Updated cost-effectiveness analysis of onabotulinumtoxinA for the prevention of headache in adults with chronic migraine who have previously received three or more preventive treatments in the UK.

Aims: OnabotulinumtoxinA is recommended by NICE for the treatment of chronic migraine. This economic evaluation provides updated estimates of the cost-effectiveness of onabotulinumtoxinA for chronic migraine using new utility estimates in an existing model structure.Methods: A previously published model was revised to include EQ-5D utility estimates from a large observational study (REPOSE; n = 633). Efficacy data were taken from the pooled phase III PREEMPT clinical trial program, while resource utilization estimates were obtained from the International Burden of Migraine Study (IBMS). The model estimated costs and quality-adjusted life years (QALYs) gained over 2 years from the UK NHS perspective.Results: OnabotulinumtoxinA treatment resulted in total discounted incremental costs of £1,204 and an incremental discounted QALY gain of 0.07 compared with placebo in patients with chronic migraine who have previously failed three or more preventive treatments, corresponding to an incremental cost-effectiveness ratio (ICER) of £16,306 per QALY gained. Scenario analysis showed that the administration of onabotulinumtoxinA by a specialist nurse rather than a neurology consultant reduced the ICER from £16,306 to £13,832 per QALY gained. Removal of the positive stopping rule recommended in current NICE guidance increased the ICER to £20,768 per QALY for onabotulinumtoxinA vs. placebo. Combining these two scenarios produced an ICER of £17,686 per QALY gained.Conclusion: NICE recommended onabotulinumtoxinA for the prevention of chronic migraine in 2012 amid concerns about the uncertainty of ICER estimates, with a positive stopping rule used to manage some of these uncertainties. Since the publication of the NICE guidance, the REPOSE study provides a more recent source of utility data based on real-world evidence. The results of analyses including these utilities suggest that the application of the positive stopping rule may not be necessary to ensure cost-effectiveness and that this aspect of the current NICE guidance for onabotulinumtoxinA may merit reconsideration.

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.

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.

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.