Impact of Vagus Nerve Stimulation for the Treatment of Drug-resistant Epilepsy on Patterns of Use and Cost of Health Care Services and Pharmacotherapy: Comparisons of the 24-Month Periods Before and After Implantation.

PURPOSE: This study examines the impact of vagus nerve stimulation (VNS) as treatment for drug-resistant epilepsy (DRE) on the use and cost of health care services and pharmacotherapy. METHODS: Using a large US health care claims database, we identified all patients with DRE who underwent VNS between January 1, 2012 and December 31, 2019. VNS implantation date was designated as the index date, and patients had to be continuously enrolled for the 24-month period before this date (preindex period). Outcomes included all-cause and epilepsy-related hospitalization, emergency department (ED) visits, and health care costs; health care claims resulting in an epilepsy diagnosis and all claims for antiseizure medications were deemed epilepsy related. Preindex data, except care related to preoperative medical clearance for VNS, were used to estimate multivariate regression models predicting outcomes during the 24-month postindex period (follow-up period). Predicted outcomes during follow-up were then compared with observed values. As a sensitivity analysis, we also replicated all analyses among subgroups defined by comorbid depression. FINDINGS: A total of 659 patients underwent VNS for DRE and met the selection criteria. For the composite outcome of all-cause hospitalizations and ED visits, observed values were 42% lower than expected during the 24-month follow-up period; for the composite outcome of epilepsy-related hospitalizations and ED visits, observed values were 49% lower (P < 0.001 for both). Observed mean total all-cause costs, inclusive of costs of the procedure, were not significantly different than expected costs by month 19 of follow-up; mean total epilepsy-related costs were comparable by month 18. Findings were similar in subgroups with and without depression, although nominally greater differences (observed - expected) were seen in those with comorbid depression. IMPLICATIONS: Our findings suggest that VNS is associated with decreased risk of hospitalization or ED visits (all cause and epilepsy related) during the 2-year period subsequent to implantation and may become cost-neutral within 2 years of implantation (vs continued medical management of DRE without VNS). Although expected outcomes were estimated based on the 24-month period before implantation, the degree to which they approximated what would have happened in the absence of VNS is unknowable. Further research is needed to better understand the extend and duration of the impact of VNS on seizure frequency and severity and health-related quality of life, including its performance among those with and without comorbid depression.

An economic evaluation of vagus nerve stimulation as an adjunctive treatment to anti-seizure medications for the treatment of drug resistant epilepsy in the United States.

INTRODUCTION: People with recurrent epileptic seizures are typically treated with anti-seizure medications (ASMs). Around a third of epilepsy patients fail to achieve an adequate response to ASMs and may be eligible to receive vagus nerve stimulation (VNS) therapy for their drug-resistant epilepsy (DRE) if they are unsuited to surgery. VNS received approval from the United States (US) Food and Drug Administration agency. However, there has to date been no comprehensive cost effectiveness evaluation of VNS within the US setting. This study was designed, using a US Medicare perspective, to estimate costs and quality-adjusted life years (QALYs) associated with VNS as an adjunct to ongoing ASM therapy, compared to ASMs alone. METHODS: We developed a cohort state transition model in Microsoft Excel, with four health states defined by different percentage reductions in seizure frequency, with a 3-month cycle and transition probabilities derived from published clinical trials and registry data. Sensitivity analyses were conducted to understand the impact of parameter uncertainty. Costs included the VNS device, placement, programming, battery changes, and removal; ASM therapy; adverse events associated with VNS (dyspnea, hoarseness, and cough); and costs associated with seizure burden (i.e. hospitalizations, emergency department visits, neurologist visits). RESULTS: Under base case assumptions, treatment with VNS was associated with a 0.385 QALY gain and a $109,678 saving per patient, when compared with ASM therapy alone. The incremental net monetary benefit (iNMB) was $128,903 at a threshold of $50,000 per QALY, with the positive iNMB indicating that VNS is a highly cost effective treatment. This result is explained by the modeled reduction in relative seizure frequency and associated reduction in healthcare resource use that the VNS group experienced. Sensitivity analyses supported this conclusion. CONCLUSIONS: VNS was evaluated as a cost effective addition to the current standard of care in the treatment of DRE in the US Medicare context.

Anti-seizure medications (ASMs) are drugs commonly prescribed to people with epilepsy to help prevent seizures from reoccurring. But these drugs do not work for all people: around a third keep having seizures despite taking the medication­a condition called drug-resistant epilepsy (DRE). For such people, their main options involve trying different combinations of ASMs, having brain surgery, or having a medical device implanted. In the United States (US), vagus nerve stimulation (VNS) therapy is approved by the Food and Drug Administration agency for DRE patients who are still having focal onset seizures despite trying ASM therapy. Using methods defined by the US evaluation body, the Institute for Clinical and Economic Review, we made an economic model to assess how cost effective VNS would be as an add-on to ASM therapy. The evaluation utilizes a previously published model, which was updated to use costs, health-related quality of life, and mortality estimates relevant to the US Medicare setting. The analysis demonstrated that VNS could generate cost savings when used as an add-on ASM treatment in the US Medicare setting. VNS may reduce the number of seizures, and subsequently improve patient quality of life and result in substantially lower costs for Medicare (e.g. in emergency and hospital care for a person having a seizure). We tested uncertainties in our model using standard methods­these additional analyses allow us to conclude that VNS is highly likely to be a cost effective addition to the current standard of care for DRE treatment from a US perspective.

Comparison of utilization and cost of healthcare services and pharmacotherapy following implantation of vagus nerve stimulation vs. responsive neurostimulation or deep brain stimulation for the treatment of drug-resistant epilepsy: analyses of a large United States healthcare claims database.

AIM: Vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) all are options for drug-resistant epilepsy (DRE). However, little is known about how the choice of neurostimulation impacts subsequent healthcare costs. MATERIALS AND METHODS: We used a large US healthcare claims database to identify all patients with epilepsy who underwent neurostimulation between 2012 and 2019. Eligible patients were identified and stratified based on procedure received (VNS vs. RNS/DBS). VNS patients were matched by propensity scoring to RNS/DBS patients. Use and cost of healthcare resources and pharmacotherapy were ascertained over the 24-month period following neurostimulation, incorporating all-cause and epilepsy-related measures. Disease-related care was defined based on diagnoses of claims for medical care and relevant pharmacotherapies. RESULTS: Seven hundred and ninety-two patients met all selection criteria. VNS patients were younger, were prescribed a higher pre-index mean number of anti-seizure medications (ASMs), and had higher pre-index levels of use and cost of epilepsy-related healthcare services. We propensity matched 148 VNS patients to an equal number of RNS/DBS patients. One year following index date (inclusive), mean total all-cause healthcare costs were 50% lower among VNS patients than RNS/DBS patients, and mean epilepsy-related costs were 55% lower; corresponding decreases at the two-year mark were 41% and 48%, respectively. LIMITATIONS: Some clinical variables, such as seizure frequency and severity, quality of life, and functional status were unavailable in the database, precluding our ability to comprehensively assess differences between devices. Administrative claims data are subject to billing code errors, inaccuracies, and missing data, resulting in possible misclassification and/or unmeasured confounding. CONCLUSIONS: After matching, VNS was associated with significantly lower all-cause and epilepsy-related costs for the two-year period following implantation. All-cause and epilepsy-related costs remained statistically significantly lower for VNS even after costs of implantation were excluded.

For some people with epilepsy, medications do not work very well. For these people, other treatment options exist. One such treatment is neurostimulation. There are three types of neurostimulators­vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). All three devices are known to reduce seizures in patients who have tried several medications. However, it is not known how these devices impact the costs of care. We compared the use and costs of medical care over 2 years between patients who got VNS and those who got RNS/DBS. Before comparing the groups, we made sure that they were balanced. Patients who got VNS were less likely than patients who got RNS/DBS to go to the hospital during the follow-up period. Patients who got VNS also had lower healthcare costs than patients who got RNS/DBS during follow-up. These differences were seen for all medical care costs. These differences also were seen in the costs of care for epilepsy. Our results suggest that the use of VNS is associated with fewer hospitalizations than RNS/DBS, and also that use of VNS is associated with lower healthcare costs than RNS/DBS.

Efficacy and safety of VNS therapy or continued medication management for treatment of adults with drug-resistant epilepsy: systematic review and meta-analysis.

Vagus nerve stimulation (VNS) Therapy® is an adjunctive neurostimulation treatment for people with drug-resistant epilepsy (DRE) who are unwilling to undergo resective surgery, have had unsuccessful surgery or are unsuitable for surgery. A systematic review and meta-analysis were conducted to determine the treatment effects of VNS Therapy as an adjunct to anti-seizure medications (ASMs) for the management of adults with DRE. A literature search was performed in August 2020 of the Medline®, Medline® Epub Ahead of Print, Embase, and the Cochrane library databases. Outcomes examined included reduction in seizure frequency, seizure freedom, ASM load, discontinuations, and serious adverse events (SAEs). Comparators included best medical practice, ASMs, low-stimulation or sham VNS Therapy. Four RCTs and six comparative observational studies were identified for inclusion. Against comparators, individuals treated with VNS had a significantly better odds of experiencing a ≥ 50% reduction in seizure frequency (OR: 2.27 [95% CI 1.47, 3.51]; p = 0.0002), a ≥ 75% reduction in seizure frequency (OR: 3.56 [95% CI 1.59, 7.98]; p = 0.002) and a reduced risk for increased ASM load (risk ratio: 0.36 [95% CI 0.21, 0.62]; p = 0.0002). There was no difference in the odds of discontinuation or the rate of SAEs between VNS versus comparators. This meta-analysis demonstrated the benefits of VNS Therapy in people with DRE, which included improvement in seizure frequency without an increase in the rate of SAEs or discontinuations, thereby supporting the consideration of VNS Therapy for people who are not responding to ASMs and those unsuitable or unwilling to undergo surgery.

Variation in access to specialist services for neurosurgical procedures in adults with epilepsy in England, a cohort study.

PURPOSE: To understand if primary consultation at tertiary epilepsy centres (TEC) in England impacts access to neurosurgical procedures (resective surgery, vagus nerve stimulator [VNS], deep brain stimulator [DBS]). METHODS: Adults with epilepsy, and with a first neurology outpatient visit (index) between 01/01/2013 and 31/12/2015, were followed using English Hospital Episode Statistics from index date to 31/12/2019. Analyses were stratified by geographic location, learning disability record, and whether the index or follow-up visits were at a TEC. RESULTS: 84,093 people were included, with mean 5.5 years of follow-up. 12.4% of the cohort had learning disability (range 10.1%-17.4% across regions). TEC consultations varied by National Health Service regions and Clinical Commissioning Groups. 37.5% of people (11.2%-75.0% across regions) had their index visit at a TEC; and, of those not initially seen at a TEC, 10.6% (6.5%-17.7%) subsequently attended a tertiary centre. During follow-up, 11.1% people (9.5%-13.2%) visited a neurosurgery department, and 2.3% of those (0.9%-5.0%) then underwent a neurosurgical procedure, mainly VNS implantation. Median time from index date to first visit at a neurosurgery centre was 7 months (range 6-8 months across regions) and 40 months to procedure (36.5-49 months, 37.0 months in people with index visit at a TEC and 49.0 months otherwise). People with learning disability were less likely to have resective surgery (<0.5% versus 1.0% in those without) and more likely to undergo VNS implantation (5.8% versus 0.8%). CONCLUSION: Although clinically recommended for suitable individuals, neurosurgical procedures in epilepsy remain uncommon even after consultation at a TEC. Geographical variation in access to TECs was present.

An economic evaluation of vagus nerve stimulation as an adjunctive treatment to anti-seizure medications for the treatment of drug-resistant epilepsy in England.

INTRODUCTION: Anti-seizure medications (ASMs) are commonly used to prevent recurring epileptic seizures, but around a third of people with epilepsy fail to achieve an adequate response. Vagus nerve stimulation (VNS) is clinically recommended for people with drug-resistant epilepsy (DRE) who are not suitable for surgery, but the cost-effectiveness of the intervention has not recently been evaluated. The study objective is to estimate costs and quality-adjusted life-years (QALYs) associated with using VNS as an adjunct to ongoing ASM therapy, compared to the strategy of using only ASMs in the treatment of people with DRE, from an English National Health Service perspective. METHODS: A cohort state transition model was developed in Microsoft Excel to simulate costs and QALYs of the VNS + ASM and ASM only strategies. Patients could transition between five health states, using a 3-month cycle length. Health states were defined by an expected percentage reduction in seizure frequency, derived from randomized control trial data. Costs included the VNS device as well as its installation, setup, and removal; ASM therapy; adverse events associated with VNS (dyspnea, hoarseness, and cough); and health-state costs associated with epilepsy including hospitalizations, emergency department visits, neurologist visits, and primary care visits. A range of sensitivity analyses, including probabilistic sensitivity analysis, were run to assess the impact of parameter and structural uncertainty. RESULTS: In the base case, VNS + ASM had an estimated incremental cost-effectiveness ratio (ICER) of £17,771 per QALY gained compared to ASMs alone. The cost-effective ICER was driven by relative reductions in expected seizure frequency and the differences in health care resource use associated therewith. Sensitivity analyses found that the amount of resource use per epilepsy-related health state was a key driver of the cost component. CONCLUSIONS: VNS is expected to be a cost-effective intervention in the treatment of DRE in the English National Health Service.

PLAIN LANGUAGE SUMMARYPeople with epilepsy are usually given anti-seizure medications (called ASMs) to help prevent their seizures from reoccurring. However, around a third of them will keep having seizures even with the medication; this is called drug-resistant epilepsy (DRE). Treatment options for DRE include, but are not limited to, surgical or therapeutic device-related interventions or trying alternative ASM combinations.In the English National Health Service (NHS), vagus nerve stimulation (VNS) therapy is recommended by the National Institute for Health and Care Excellence (NICE) for DRE patients who are still having seizures despite trying several different ASMs, and who cannot have brain surgery. Following NICE technical standards, we developed an economic model to test whether VNS would be a cost-effective add-on to ASM therapy. The model uses current costs for VNS therapy and takes a more nuanced approach to the longevity of the VNS device than previous research did.Results showed that adding VNS to ASMs can be a cost-effective way to treat DRE in today's NHS in England. VNS reduces the number of seizures, which is expected to improve patients' quality of life and cut NHS costs that would otherwise have been needed to look after patients who had a seizure (for example, emergency visits or inpatient hospital stays). Sensitivity analyses tested aspects of uncertainty in our model. These highlighted the need to further understand the relationship between seizures, their severity, and health care usage if we want to make improved cost-effectiveness analyses about DRE in the future.

Correction to: Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy.

The article "Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy", written by Molly F. Purser, Deirdre M. Mladsi, Alan Beckman, Francesca Barion, John Forsey was originally published electronically on the publisher's internet portal (currently SpringerLink) on August 24, 2018 without open access.

Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy.

INTRODUCTION: The objective was to estimate, from the perspective of a managed care organization in the United States, the budget impact and effect on health outcomes of expanded use of vagus nerve stimulation [VNS (VNS Therapy®)] among patients aged ≥ 12 years with drug-resistant epilepsy (DRE) with partial-onset seizures. METHODS: An Excel model was developed to compare the costs of continued anti-epileptic drug (AED) treatment with the costs of VNS plus AED treatment. The number of people eligible for VNS was estimated using published prevalence data and an estimate of the percentage of eligible patients currently without VNS. Costs included VNS device, placement, programming, and battery changes; adverse events associated with VNS (cough, voice alteration, device removal resulting from surgical site infection); AEDs; and seizure-related costs affected by seizure frequency, which affects resource utilization (i.e., hospitalizations, emergency department visits, neurologist visits). To estimate the potential savings with VNS due to a reduction in seizure frequency, the budget impact model uses the results of an underlying Markov model to estimate seizure-related costs by seizure frequency. Transitions occurred among four health states, defined by number of seizures per month (i.e., seizure-free, ≤ 1, > 1 to < 10, ≥ 10) on a 3-month cycle based on published clinical trials and registry data. RESULTS: VNS resulted in an estimated net cost savings, on average, over 5 years, due to the expected reduction in seizure frequency. The initial cost of the VNS device, placement, and programming was estimated to be offset 1.7 years after VNS device placement. Reductions in hospitalizations were the main contributor to the cost savings with VNS. CONCLUSIONS: VNS is a proven intervention that offers a long-term solution for patients with DRE by reducing seizure frequency, which leads to lower resource utilization and lower costs. FUNDING: LivaNova PLC.

Asthma outcomes and costs of therapy with extrafine beclomethasone and fluticasone.

BACKGROUND: Characteristics of inhaled corticosteroids (ICSs) differ, but data comparing the real-life effectiveness of various ICSs for asthma are lacking. OBJECTIVE: We sought to compare real-life asthma outcomes and costs of extrafine hydrofluoroalkane (HFA)-beclomethasone and fluticasone administered through a pressurized metered-dose inhaler. METHODS: This retrospective matched cohort study examined database markers of asthma control from a large US longitudinal health care claims database over 1 baseline and 1 outcome year for 10,312 patients with asthma aged 12 to 80 years receiving their first ICS as HFA-beclomethasone or fluticasone and matched on baseline demographic characteristics and asthma severity. RESULTS: Patients started on HFA-beclomethasone had significantly higher odds (adjusted odds ratio, 1.19; 95% CI; 1.08-1.31) of achieving overall control (risk and impairment), which was defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection and less than 2 puffs per day of short-acting ß-agonist; they also experienced a lower rate of respiratory-related hospitalizations or referrals (adjusted rate ratio, 0.82; 95% CI, 0.73-0.93) than patients started on fluticasone. Other database outcome measures were similar in the 2 cohorts. Prescribed HFA-beclomethasone doses were lower (P < .001) than fluticasone doses (median, 320 µg/d [interquartile range, 160-320 µg/d] vs 440 µg/d [interquartile range, 176-440 µg/d]). Adjusted respiratory-related health care costs were significantly lower for HFA-beclomethasone than fluticasone (mean, $1869 [95% CI, $1727-$2032] vs $2259 [95% CI, $2111-$2404]), representing a mean annual savings of $390 (95% CI, $165-$620) per patient prescribed HFA-beclomethasone rather than fluticasone. CONCLUSIONS: Asthma treatment outcomes were similar or better with HFA-beclomethasone prescribed at significantly lower doses and with lower costs than fluticasone.