Cost-effectiveness analysis of intravenous levetiracetam versus intravenous phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury

Rashid Kazerooni1, Mark Bounthavong1,21Pharmacoeconomics/Formulary Management, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; 2UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USAObjective: There has been growing interest in newer anti-epileptic drugs (AEDs) for seizure prophylaxis in the intensive care setting because of safety and monitoring issues associated with conventional AEDs like phenytoin. This analysis assessed the cost-effectiveness of levetiracetam versus phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury (TBI).Methods: A cost-effectiveness analysis was conducted from the US hospital perspective using a decision analysis model. Probabilities of the model were taken from three studies comparing levetiracetam and phenytoin in post neurosurgery or TBI patients. The outcome measure was successful seizure prophylaxis regimen (SSPR) within 7 days, which was defined as patients who did not seize or require discontinuation of the AED due to adverse drug reactions (ADRs). One-way sensitivity analyses and probabilistic sensitivity analysis were conducted to test robustness of the base-case results.Results: The total direct costs for seizure prophylaxis were $8,784.63 and$8,743.78 for levetiracetam and phenytoin, respectively. The cost-effectiveness ratio of levetiracetam was $10,044.91 per SSPR compared to$11,525.63 per SSPR with phenytoin. The effectiveness probability (patients with no seizures and no ADR requiring change in therapy) was higher in the levetiracetam group (87.5%) versus the phenytoin group (75.9%). The incremental cost effectiveness ratio for levetiracetam versus phenytoin was 360.82 per additional SSPR gained.Conclusions: Levetiracetam has the potential to be more cost-effective than phenytoin for early onset seizure prophylaxis after neurosurgery if the payer’s willingness-to-pay is greater than 360.82 per additional SSPR gained.Keywords: phenytoin, levetiracetam, seizure prophylaxis, cost-effectiveness, traumatic brain injury (TBI), and neurosurger

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

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

Retrospective cohort study of anti-tumor necrosis factor agent use in a veteran population.

Introduction. Anti-tumor necrosis factor (TNF) agents are effective for several immunologic conditions (rheumatoid arthritis (RA), Crohn's disease (CD), and psoriasis). The purpose of this study was to evaluate the efficacy and safety of anti-TNF agents via chart review. Methods. Single-site, retrospective cohort study that evaluated the efficacy and safety of anti-TNF agents in veterans initiated between 2010 and 2011. Primary aim evaluated response at 12 months post-index date. Secondary aims evaluated initial response prior to 12 months post-index date and infection events. Results. A majority of patients were prescribed anti-TNF agents for CD (27%) and RA (24%). Patients were initiated on etanercept (41%), adalimumab (40%), and infliximab (18%) between 2010 and 2011. No differences in patient demographics were reported. Response rates were high overall. Sixty-five percent of etanercept patients, 82% of adalimumab patients, and 59% of infliximab patients were either partial or full responders, respectively. Approximately 16%, 11%, and 12% of etanercept, adalimumab, and infliximab were non-responders, respectively. Infections between the groups were non-significant. Etanercept and adalimumab patients had higher but non-significant odds of being a responder relative to infliximab. Conclusions. Most patients initiated with anti-TNF agent were responders at 12 months follow-up for all indications in a veteran population

Association of copayment with likelihood and level of adherence in new users of statins: a retrospective cohort study.

BackgroundStatins remain a fundamental component of pharmacologic therapy for hyperlipidemia. Health benefits of statin therapy are jeopardized when adherence is reduced.ObjectivesTo (a) assess the association between copayment and copayment type on statin adherence using 2 different thresholds of adherence and (b) identify the incremental change in statin adherence associated with presence of copayment and copayment type.MethodsWe executed a retrospective cohort study of new users of statins with dyslipidemia from the Veterans Health Administration (VHA) within the Veterans Integrated Service Network 22 who initiated a statin between November 30, 2006, and December 2, 2007. We used exposure categories of Any Copayment versus No Copayment, indicating a patient had a copayment or had no copayment in order to obtain medications, respectively. As a separate analysis, we varied the exposures to the standard VHA copayment categories: (a) Service-Connected (SC) Copayment (patients with service-related injury), (b) Non-Service-Connected (NSC) Copayment (patients without a service-related injury), and (c) No Copayment. Using each set of exposures, we conducted separate multiple logistic regression analyses using 2 different adherence outcomes based on medication possession ratio (MPR) threshold: (1) adherence defined as MPR ≥ 0.8 and (2) adherence defined as MPR ≥ 0.9. We then proceeded with multiple linear regression models to determine the incremental change in MPR associated with the 2 sets of exposures. Subjects were required to be enrolled in VHA services for at least 2 years prior to index date and throughout the 1-year study period.ResultsA total of 4,886 subjects were identified for analysis based on the inclusion and exclusion criteria. Patients who did not pay a copayment for their statin medications were more likely to have adherence rates of ≥ 0.8 MPR and ≥ 0.9 MPR relative to the No Copayment Group with odds ratios (OR) of 1.19 (95% CI = 1.03-1.37) and 1.28 (95% CI = 1.11-1.48), respectively. The second analysis applied the VHA exposure categories of SC Copayment, NSC Copayment, and No Copayment. Using the 0.8 MPR or greater adherence threshold, the No Copayment group was associated with an increased likelihood of adherence versus the SC Copayment category as reference group with an OR of 1.31 (95% CI = 1.10-1.58). The NSC Copayment was associated with a nonsignificant increase in odds of adherence at the 0.8 MPR level or greater with OR of 1.12 (95% CI = 0.98-1.39). Using the 0.9 MPR level or greater, adherence threshold findings were similar. The No Copayment group produced an OR of 1.42 (95% CI = 1.17-1.71) compared with the SC Copayment group. The NSC Copayment group was associated with a nonsignificant increase in odds of adherence at the 0.9 MPR level or greater with an OR of 1.12 (95% CI = 0.97-1.38).The No Copayment group was associated with an increase in MPR of 0.02 (95% CI = 0.002-0.035) versus the Any Copayment category. Using the VHA copayment categories, we observed an increase in MPR for the No Copayment group versus the SC Copayment group of 0.03 (95% CI = 0.01-0.05). The NSC Copayment group was associated with a nonsignificant increase in MPR versus the SC Copayment group of 0.02 (95% CI = -0.003-0.036).ConclusionsPatients without out-of-pocket payments for their statins were more likely to adhere to therapy. Patients who pay a copayment for their statin medications were also compared with each other based on whether they (a) received any of their nonstatin prescriptions without a copayment or (b) paid a copayment on all of their prescriptions including statins. Our findings suggest that, among those that pay for their statins, patients are less adherent to their statins if other medications they are prescribed are copayment free. Thus, patient consumption behavior may be influenced by the relative cost of medications in patient prescription lists. Additional counseling on the necessity of adherence should be given to patients paying a copayment for their statin prescriptions

Association of copayment with likelihood and level of adherence in new users of statins: a retrospective cohort study.

BackgroundStatins remain a fundamental component of pharmacologic therapy for hyperlipidemia. Health benefits of statin therapy are jeopardized when adherence is reduced.ObjectivesTo (a) assess the association between copayment and copayment type on statin adherence using 2 different thresholds of adherence and (b) identify the incremental change in statin adherence associated with presence of copayment and copayment type.MethodsWe executed a retrospective cohort study of new users of statins with dyslipidemia from the Veterans Health Administration (VHA) within the Veterans Integrated Service Network 22 who initiated a statin between November 30, 2006, and December 2, 2007. We used exposure categories of Any Copayment versus No Copayment, indicating a patient had a copayment or had no copayment in order to obtain medications, respectively. As a separate analysis, we varied the exposures to the standard VHA copayment categories: (a) Service-Connected (SC) Copayment (patients with service-related injury), (b) Non-Service-Connected (NSC) Copayment (patients without a service-related injury), and (c) No Copayment. Using each set of exposures, we conducted separate multiple logistic regression analyses using 2 different adherence outcomes based on medication possession ratio (MPR) threshold: (1) adherence defined as MPR ≥ 0.8 and (2) adherence defined as MPR ≥ 0.9. We then proceeded with multiple linear regression models to determine the incremental change in MPR associated with the 2 sets of exposures. Subjects were required to be enrolled in VHA services for at least 2 years prior to index date and throughout the 1-year study period.ResultsA total of 4,886 subjects were identified for analysis based on the inclusion and exclusion criteria. Patients who did not pay a copayment for their statin medications were more likely to have adherence rates of ≥ 0.8 MPR and ≥ 0.9 MPR relative to the No Copayment Group with odds ratios (OR) of 1.19 (95% CI = 1.03-1.37) and 1.28 (95% CI = 1.11-1.48), respectively. The second analysis applied the VHA exposure categories of SC Copayment, NSC Copayment, and No Copayment. Using the 0.8 MPR or greater adherence threshold, the No Copayment group was associated with an increased likelihood of adherence versus the SC Copayment category as reference group with an OR of 1.31 (95% CI = 1.10-1.58). The NSC Copayment was associated with a nonsignificant increase in odds of adherence at the 0.8 MPR level or greater with OR of 1.12 (95% CI = 0.98-1.39). Using the 0.9 MPR level or greater, adherence threshold findings were similar. The No Copayment group produced an OR of 1.42 (95% CI = 1.17-1.71) compared with the SC Copayment group. The NSC Copayment group was associated with a nonsignificant increase in odds of adherence at the 0.9 MPR level or greater with an OR of 1.12 (95% CI = 0.97-1.38).The No Copayment group was associated with an increase in MPR of 0.02 (95% CI = 0.002-0.035) versus the Any Copayment category. Using the VHA copayment categories, we observed an increase in MPR for the No Copayment group versus the SC Copayment group of 0.03 (95% CI = 0.01-0.05). The NSC Copayment group was associated with a nonsignificant increase in MPR versus the SC Copayment group of 0.02 (95% CI = -0.003-0.036).ConclusionsPatients without out-of-pocket payments for their statins were more likely to adhere to therapy. Patients who pay a copayment for their statin medications were also compared with each other based on whether they (a) received any of their nonstatin prescriptions without a copayment or (b) paid a copayment on all of their prescriptions including statins. Our findings suggest that, among those that pay for their statins, patients are less adherent to their statins if other medications they are prescribed are copayment free. Thus, patient consumption behavior may be influenced by the relative cost of medications in patient prescription lists. Additional counseling on the necessity of adherence should be given to patients paying a copayment for their statin prescriptions

Real-World Six-Year National Cost-Minimization Analysis of IncobotulinumtoxinA and OnabotulinumtoxinA in the VA/DoD Healthcare Systems.

PURPOSE: This study sought to perform a real-world, long-term cost-minimization analysis for incobotulinumtoxinA (Xeomin®) versus onabotulinumtoxinA (Botox®), given the established non-inferiority when utilized at similar doses. METHODS: The Department of Veterans Affairs (VA) and Department of Defense (DoD) national healthcare systems were included in this analysis. Real-world purchase data for incobotulinumtoxinA were used to estimate the direct drug costs between calendar years 2014 and 2019. Publicly available federal pharmaceutical prices (Federal Supply Schedule and Big 4) were used. The primary outcome was the difference in total direct costs nationally for incobotulinumtoxinA (real-world) versus having hypothetically utilized onabotulinumtoxinA (projected) for similar utilization. Sites utilizing ≥100 vials (of 100 Unit equivalents) of incobotulinumtoxinA annually were categorized as major adopters. IncobotulinumtoxinA 50 Unit vials were assumed to be an alternative to a 100 Unit vial of onabotulinumtoxinA for 50% of such vial purchases in the base case scenario to account for differences in wastage. RESULTS: Over the six-year study time frame, 156 sites (76.8%) utilized incobotulinumtoxinA of the 203 total VA healthcare systems and DoD medical centers. Of these sites, 67 were major adopters for at least one year, with a mean of 3.4 years spent as a major adopter over the study period. Average annual savings per major adopter was $105,782. IncobotulinumtoxinA costs for all VA/DoD sites was$46.39 million for the six-year period versus a projected $71.92 million onabotulinumtoxinA cost-a total savings of$25.53 million (35.5% relative reduction). Approximately, 82.8% of savings stemmed from lower drug acquisition cost ($21.14 million) and 17.2$4.39 million) was related to reduced wastage. It was estimated that a total of 9958 extra onabotulinumtoxinA 100 Unit vials would have been wasted during the six-year period, translating to the need for a 5.9% increase in vial purchases versus incobotulinumtoxinA. CONCLUSION: Meaningful cost savings were realized related to incobotulinumtoxinA adoption over a long-term time frame in the VA/DoD healthcare systems