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.

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 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.

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.

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.

Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug.

Objective: The purpose of this article is to review the literature for both 3,4-diaminopyridine (3,4-DAP) and amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). Amifampridine (Firdapse) is the salt form of 3,4-DAP and was approved by the Food and Drug Administration for the treatment of LEMS. Data Sources: PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: amifampridine, 3,4-diaminopyridine, and Lambert-Eaton myasthenic syndrome. Completed trials were also reviewed at clinicaltrials.gov. Study Selection and Data Extraction: Criteria for article inclusion consisted of human subjects, age ≥18 years, phase II or III clinical trials, and English language for both drugs. Observational and pharmacokinetic studies for amifampridine were also included. Data Synthesis: Prior to the approval of amifampridine, 3,4-DAP was first-line for the management of LEMS symptoms. Two phase III trials have evaluated amifampridine to confirm efficacy, both showing superiority over placebo in the management of LEMS symptoms, with minimal adverse effects. A significant improvement in both quantitative myasthenia gravis scores and Subjective Global Impression scores was established at days 4 and 14. Relevance to Patient Care and Clinical Practice: With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Conclusions: Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.

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 of overactive bladder treatments: from the US payer perspective.

AIM: To assess the cost-effectiveness of onabotulinumtoxinA (onabotA), implantable sacral nerve stimulation devices, percutaneous tibial nerve stimulation, anticholinergic medications and mirabegron compared with best supportive care (BSC) for management of refractory overactive bladder (OAB). METHODS: A Markov model was developed to compare the cost-effectiveness of treatment options with BSC over a 10-year time horizon. Resource utilization, discontinuation rates and costs were derived from unpublished and published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported. RESULTS: Treatment with onabotA 100U produced the largest gain in QALYs (7.179) and lowest estimated incremental cost-effectiveness ratio ($32,680/QALY) of all assessed treatments compared with BSC. CONCLUSION: Compared with BSC, onabotA 100U was the most cost-effective treatment option for patients with refractory OAB.

Análisis coste-utilidad de dos formulaciones de toxina botulínica de tipo A en el tratamiento del blefaroespasmo y la distonía cervical en España / Cost-utility analysis of two formulations of botulinum toxin type A in the treatment of blepharospasm and cervical dystonia in Spain

Introducción. Las formulaciones de toxina botulínica de tipo A, incobotulinumtoxinA (Inco-TBA) y onabotulinumtoxinA (Ona-TBA), han demostrado eficacia y seguridad similar en los estudios de distonías focales en los que se han comparado. Objetivo. Realizar un análisis coste-utilidad de Inco-TBA, administrada en intervalos flexibles, frente a Ona-TBA, administrada en intervalos fijos, en el tratamiento del blefaroespasmo y la distonía cervical. Pacientes y métodos. Un modelo de Markov probabilístico estimó, desde la perspectiva del Sistema Nacional de Salud español y en un horizonte de cinco años, el coste (euros, 2017) y el resultado (años de vida ajustados a calidad, AVAC) del tratamiento del blefaroespasmo y la distonía cervical mediante intervalos flexibles con Inco-TBA (6-20 semanas) y fijos con Ona-TBA (12 semanas). Se asume que los síntomas reaparecerán después de un tiempo en ambos. El resultado se expresó como ratio coste-utilidad incremental (RCUI). Resultados. El coste de la Inco-TBA y la Ona-TBA fue, respectivamente, de 3.742 y 3.366 euros en el blefaroespasmo y de 6.673 y 6.419 euros en la distonía cervical. Los pacientes tratados con Inco-TBA permanecieron asintomáticos 22,12 y 21,34 semanas más que los tratados con Ona-TBA, lo que resultó 3,040 y 3,012 AVAC, respectivamente, en el blefaroespasmo, y 3,471 y 3,401 AVAC, respectivamente, en la distonía cervical. En todos los casos, las diferencias presentaron significación estadística. La RCUI fue de 13.576 y 4.158 euros/AVAC, respectivamente. Conclusiones. El tratamiento del blefaroespasmo y la distonía cervical con Inco-TBA, administrada siguiendo un esquema posológico de intervalos flexibles, constituye una alternativa terapéutica eficiente en España

Introduction. Studies on focal dystonia showed that the formulations of botulinum toxin type A, incobotulinumtoxin-A (Inco-BTA) and onabotulinumtoxin-A (Ona-BTA), have equivalent efficacy and safety. Aim. To carry-out a cost-utility analysis of Inco-BTA administered on flexible intervals vs. Ona-BTA on a fixed interval, in the treatment of blepharospasm and cervical dystonia. Patients and methods. A probabilistic Markov model was designed to estimate costs (euros, 2017) and benefits (qualityadjusted life years, QALY), from the Spanish National Health Service perspective and on a 5-year time horizon, of treatment of blepharospasm and cervical dystonia with Inco-BTA (6-12 month flexible intervals) versus Ona-BTA (12-month fixed intervals). It is assumed that symptoms will re-emerge some time later in both options. Result was expressed as incremental cost-utility ratio (ICUR). Results. Inco-BTA and Ona-BTA costs were 3,742 and 3,366 euros respectively, in blepharospasm, and 6,673 and 6,419 euros in cervical dystonia. Patients treated with Inco-BTA remained asymptomatic for 22.12, and 21.34 more weeks than those treated with Ona-BTA, leading in 3.040 and 3.012 QALY, respectively, in blepharospasm, and 3.471 and 3.401 QALY, respectively, in cervical dystonia. Differences showed statistical significance in all cases. ICUR was estimated as 13,576 and 4,158 euros/QALY in blepharospasm and cervical dystonia, respectively. Conclusions. Treatment of blepharospasm and cervical dystonia with Inco-BTA is a cost-effective therapeutic alternative in Spain, based on the flexibility of their administration

To switch from Botox to Dysport in children with CP, a real world, dose conversion, cost-effectiveness study.

BACKGROUND AND OBJECTIVES: Children with cerebral palsy (CP) are routinely treated with botulinum toxin A (BoNT-A). Two non dose-equivalent and differently priced products, Botox and Dysport are used. Depending on the conversion one of the products is considerably cheaper. However, the dose conversion factors studied to date have varied widely and relevant studies have not included children. Our objective here was to compare the efficacy and health economics of the switch from Botox to Dysport in children with CP when conversion was set to 1:2. Specifically were these treatments perceived as equivalent in terms of efficacy, duration and side-effects and were the drug cost lowered by using Dysport. METHODS: This prospective, real-world, cost-effectiveness population-based observational study included all children with CP, (n = 159) mean age 9.4 years (SD, 4.3), in the larger Stockholm area who received BoNT-A between September 1, 2014, and December 31, 2015. Parents reported the efficacy, duration and side-effects of previous treatment while physicians reported doses and goals set by children and parents for the present treatment. Drug acquisition costs were provided by county administrators. RESULTS: In connection with 341 visits caregivers reported comparable effects of similar duration with these products, with few, similar and transient side-effects. The drug-cost per treatment was 4029 SEK for Botox and 2380 SEK in the case of Dysport. CONCLUSION: When Botox was replaced by a two-fold higher Unit dose of Dysport (conversion 1:2) parents perceived the treatment of their children with CP to be equally effective while the cost was 41% lower according to procured prices.

What's new in multiple sclerosis spasticity research? Poster session highlights.

Each year at the Multiple Sclerosis Experts Summit, relevant research in the field of multiple sclerosis spasticity is featured in poster sessions. The main studies presented at this year's meeting are summarized herein.

The Role of Injectables in Aesthetic Surgery: Financial Implications.

Background: The plastic surgeon competes with both core and noncore physicians and surgeons for traditional cosmetic procedures. In 2007, the American Society for Aesthetic Plastic Surgery (ASAPS) and the American Society of Plastic Surgeons (ASPS) joined efforts to form a Cosmetic Medicine Task Force to further analyze this trend. Objectives: Our objective is to document and quantify the patient capture and total collections generated in a single surgeon's practice exclusive from Botulinum Toxin A and filler injections over a 10-year period. We subsequently identified the effect and importance that fillers and Botulinum Toxin A have on an active cosmetic practice. Methods: A retrospective chart review of all male and female patients who received Botulinum Toxin A or soft tissue filler injections (noninvasive aesthetic treatment) in a single surgeons practice from January 2004 to December 2013 was undertaken. Only those patients new to the practice and who were exclusively seeking out Botulinum Toxin A or fillers were included in the study. Chart review then identified which of these selected patients ultimately underwent invasive aesthetic surgery during this 10-year period. Noninvasive and invasive aesthetic surgery total collections were calculated using billing records. Results: From January 2004 to December 2013, 375 patients entered the senior surgeon's practice specifically requesting and receiving noninvasive aesthetic treatments. Of these 375 patients, 59 patients (15.7%) subsequently underwent an aesthetic surgery procedure at an average of 19 months following initial noninvasive aesthetic treatment. Of these 375 patients, 369 were female and 6 were male. The most common initial invasive aesthetic procedure performed after injectable treatment included 22 facelifts (18.5%), 21 upper eyelid blepharoplasties (17.6%), and 15 endoscopic brow lifts (12.6%). Total collections from noninvasive aesthetic sessions and invasive surgery combined represented US$762,470 over this 10-year span. This represented US$524,771 and US$396,166 in total collections for injectables and surgery respectively. Conclusions: Noninvasive aesthetic surgery is a critical part of a plastic surgery practice. A measurable and significant number of patients who sought out a single plastic surgeon exclusively for noninvasive treatment ultimately underwent traditional invasive cosmetic surgical procedures.

Cosmetic Practitioners Take Huge Risks Purchasing and Administering Illegal Botulinum Toxin Drug Products.

In their article "Importing Injectables" in the September 2014 issue of the Journal of Drugs in Dermatology, Dr. Kenneth Beer and Karen Rothschild highlighted the possible harm to patients and practitioners from the use of unapproved botulinum toxin products - eg, Botox, Dysport, Xeomin, and Myobloc - and other cosmetic prescription drug products purchased from foreign or unlicensed suppliers.1 In the intervening years, the accuracy of their critique has been repeatedly demonstrated, as the dangers to patients' health, as well as to cosmetic practitioners' liberty, has only increased.

Regional disparities in botulinum toxin A (BoNT-A) therapy for spasticity in Sweden: budgetary consequences of closing the estimated treatment gap.

OBJECTIVES: As no national treatment guidelines for spasticity have been issued in Sweden, different regional treatment practices may potentially occur. This study examines botulinum toxin A (BoNT-A) treatment for spasticity on a regional level in Sweden and presents budgetary consequences of closing the estimated treatment gap. MATERIALS AND METHODS: Prevalence of spasticity in Sweden was estimated from published data. Regional sales data for BoNT-A were acquired from IMS Health. A set proportion of hospital BoNT-A use was assumed to represent treatment of spasticity. Total intervention cost of BoNT-A treatment was gathered from healthcare regional tariffs, while costs associated with spasticity were derived from publications on multiple sclerosis and stroke. RESULTS: Results show that the regional variation in treatment of spasticity with BoNT-A is large, with approximately every fourth patient being treated in Southern healthcare region compared to every tenth in the Stockholm-Gotland or Western healthcare regions. The incremental cost of filling the reported treatment gap was also assessed and was estimated at around 9.4 million EUR. However, for the incremental cost to be offset by savings in spasticity-related costs, only a small proportion of treatment responders (defined as patients transitioning to a lower severity grade of spasticity) was required (12%). CONCLUSIONS: The study revealed apparent regional disparities of BoNT-A treatment for spasticity in Sweden. The results further suggest that the incremental cost of eliminating the treatment gap has a high probability of being offset by savings in direct costs, even at a low proportion of the patients reaching clinical improvement.

Cost-minimization analysis in the treatment of spasticity in children with cerebral palsy with botulinum toxin type A: an observational, longitudinal, retrospective study.

OBJECTIVE: Cost-minimization analysis of onabotulinumtoxinA and abobotulinumtoxinA, taking into account the real dose administered to children with spasticity associated with dynamic equinus foot deformity due to cerebral palsy. METHOD: A single centre, observational, longitudinal, and retrospective study which included spastic paediatric patients aged 2-to-18-years and treated with onabotulinumtoxinA or abobotulinumtoxinA from December 1995 to October 2012, in the Paediatric Neurology Unit of a first-level Spanish hospital. A longitudinal analysis of spasticity severity was made to confirm the similar efficacy of both treatments. Cost minimization was analyzed using the dose administered and the direct costs (pharmacological and medical visits costs) from the perspective of the National Health System (in euros from 2016). RESULTS: We analyzed 895 patients with paediatric spasticity: 543 were treated only with onabotulinumtoxinA, 292 only with abobotulinumtoxinA, and 60 with both treatments. The mean doses administered were 5.44 U/kg (SD = 2.17) for onabotulinumtoxinA, and 14.73 U/kg (5.26) for abobotulinumto xinA. The total annual direct cost (pharmacological and medical visits) was € 839.56 for onabotulinumtoxinA and € 631.23 for abobotulinumtoxinA, which represents a difference of € 208.34 per year in favour of treatment with abobotulinumtoxinA. CONCLUSIONS: It has been demonstrated that in real clinical practice, the cost per patient and year for treatment of paediatric spasticity was lower when abobotulinumtoxinA was used.

Objetivo: Estudio de minimización de costes de onabotulinumtoxinA y de abobotulinumtoxinA, teniendo en cuenta la dosis real administrada, en ninos con espasticidad asociada con la deformidad dinámica del pie equino debida a parálisis cerebral. Método: Estudio unicéntrico, observacional, longitudinal y retrospectivo que incluyó pacientes pediátricos espásticos entre 2 y 18 anos tratados con onabotulinumtoxinA o abobotulinumtoxinA, entre diciembre del 1995 y octubre del 2012, en el Servicio de Neurología Pediátrica de un hospital espanol de primer nivel. Se realizó un análisis longitudinal de la gravedad de la espasticidad para confirmar la similar efectividad de ambos tratamientos y proceder al análisis de minimización de costes que contempló las dosis infiltradas y los costes directos (costes farmacológicos y de visitas) desde la perspectiva del Sistema Nacional de Salud (euros 2016). Resultados: Se analizaron 895 pacientes con espasticidad infantil, 543 fueron tratados únicamente con onabotulinumtoxinA, 292 con abobotulinumtoxinA y 60 con ambos tratamientos. Las dosis medias infiltradas obtenidas fueron de 5,44 U/kg (DE = 2,17) para las infiltraciones con onabotulinumtoxinA y de 14,73 U/kg (5,26) para las infiltraciones con abobotulinumto xinA. El coste directo anual total (farmacológico y visitas) fue de 839,56 € para onabotulinumtoxinA y de 631,23 € para abobotulinumtoxinA, lo que supone una diferencia de 208,34 € al ano a favor del tratamiento con abobotulinumtoxinA. Conclusiones: Se ha mostrado que en práctica clínica real el coste por paciente y ano del tratamiento de la espasticidad infantil resulta más económico con la utilización de abobotulinumtoxinA.

Drug Development and Challenges for Neuromuscular Clinical Trials.

Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.7 billion. Nevertheless, according to the Centers for Medicare and Medicaid services, prescription drugs constituted only 9 % of each health care dollar spent in USA in 2013. Examples of challenges encountered in neuromuscular clinical trials include lack of validated patient-reported outcome tools, blinding issues, and the use of placebo in addition to lack of health authority guidance for orphan diseases. Patient enrollment challenge is the leading cause of missed clinical trial deadlines observed in about 80 % of clinical trials, resulting in delayed availability of potentially life-saving therapies. Another specific challenge introduced by recent technology is the use of social media and risk of bias. Sharing personal experiences while in the study could easily introduce bias among patients that would interfere with accurate interpretation of collected data. To minimize this risk, recent neuromuscular studies incorporate as an inclusion criterion the patient's agreement not to share any of study experiences through social media with other patients during the study conduct. Consideration of these challenges will allow timely response to the high unmet medical needs for many neuromuscular diseases.

Botulinum toxin A for treating spasticity in adults: costly for French hospitals?

INTRODUCTION: Intramuscular injection of botulinum toxin (BoNTA) is one of the primary treatments for focal spasticity. This treatment is considered costly and the level of reimbursement by health insurance has been decreasing in many countries for several years. The aim of this study was to determine the real cost of treating spasticity with BoNTA and to compare this with the level of reimbursement by the national health insurance in France in 2008 and with a new fee, specific to the injection of BoNTA in ambulatory services. METHOD: A single-center, retrospective study using the 2008 database from a French secondary-care day-hospital unit (treating spasticity in adults with sequelae of stroke, multiple sclerosis or traumatic brain injuries). The level of reimbursement by the French ministry of health for BoNTA treatment for adults with spasticity constituted the "calculated cost" and corresponded to the hospital's "budget". The "real cost" (incurred by the hospital) included the sum of staffing and material costs as well as the number of toxin vials used. The calculated costs for 2009 and 2013 were based on the levels of reimbursement during those years. The difference between real and calculated cost for 2009 and 2013 was estimated considering that the real cost of 2008 was stable. RESULTS: In 2008, 364 patients received BoNTA, resulting in 870 day-hospital admissions. The calculated cost was 459,056€/year and the real cost was 567,438€/year (equivalent to 4.27€/day/patient). The total budget deficit (hospital income minus hospital costs) was 108,383€. The deficit was estimated at 222,892€ in 2009 and 241,188€ in 2013. CONCLUSION: The daily cost of BoNTA treatment for spasticity is reasonable; however, because of the level of reimbursement by the national health insurance in France, the treatment is costly for French hospitals.