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Supplements Noninvasive Vagus Nerve Stimulation for Migraine and Primary Headache Disorders: Efficacy, Cost, and Impact on Quality of Life
Review of Evidence on Noninvasive Vagus Nerve Stimulation for Treatment of Migraine: Efficacy, Safety, and Implications
Mkaya Mwamburi, MD, PhD; Andrew T. Tenaglia, BA; Eric J. Leibler; and Peter S. Staats, MD, MBA
Noninvasive Vagus Nerve Stimulation in a Primary Care Setting: Effects on Quality of Life and Utilization Measures in Multimorbidity Patients With or Without Primary Headache
Iain Strickland, PhD, BSc; Mkaya Mwamburi, MD, PhD; Steven Davis BSc; James C.R. Ward, MBBS; Janet Day, MBChB; Andrew T. Tenaglia, BA; Eric J. Leibler; and Peter S. Staats, MD, MBA
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Cost-effectiveness of Noninvasive Vagus Nerve Stimulation for Acute Treatment of Episodic Migraine and Role in Treatment Sequence Strategies
Mkaya Mwamburi, MD, PhD; Andrew T. Tenaglia, BA; Eric J. Leibler; and Peter S. Staats, MD, MBA

Cost-effectiveness of Noninvasive Vagus Nerve Stimulation for Acute Treatment of Episodic Migraine and Role in Treatment Sequence Strategies

Mkaya Mwamburi, MD, PhD; Andrew T. Tenaglia, BA; Eric J. Leibler; and Peter S. Staats, MD, MBA
Migraine affects 15% of the population in the United States and is associated with comorbidities, with an estimated economic burden of $78 billion annually. GammaCore is used adjunctively with current standard of care and abortive medications and has shown to be superior in acute treatment of episodic migraine compared to sham. However, the economic impact has not been characterized for this indication. We conducted a cost-effectiveness analyses for 2 hypothetical scenarios: a primary model for treatment options gammaCore plus standard of care compared to standard of care alone for acute treatment of migraine; and a secondary model for treatment sequence strategies where acute treatment with gammaCore or standard of care each prior to erenumab prevention compared to initiating erenumab prevention with no prerequisite. The time horizon for the model is 1 year, using a payer perspective. GammaCore plus standard of care arm was dominant over standard of care alone in the primary model. The mean costs for gammaCore plus standard of care arm and standard of care individually were $9678 and $10,010, respectively. The mean quality of life-years for gammaCore plus standard of care arm and standard of care alone were 0.67, and 0.63, respectively. For the secondary model, the mean costs for gammaCore followed by erenumab, standard of care followed by erenumab and initiating with erenumab with no prior gammaCore or standard of care treatment were $10,678, $11,583, and $13,766. The corresponding mean for quality of life-years were 0.70, 0.67, and 0.65, respectively. For gammaCore dominance, ie, in this scenario, patients were more satisfied on gammaCore, to not need erenumab for preventative therapy lower mean costs and represents savings for payers. This was driven by efficacy, improvement in quality of life, and reduction in costs of care associated with successful treatment of migraine attacks. These findings provide new economic evidence to support value for coverage for gammaCore.
Am J Manag Care. 2018;24:-S0
Migraine affects approximately 15% of the US population, with an estimated economic burden of $78 billion annually.1,2 GammaCore (noninvasive vagus nerve stimulation [nVNS]; electroCore, Basking Ridge, NJ), was approved by the FDA in January 2018

(Figure 1) and offers a viable option for abortive therapy for many of these patients with migraine.3 Available treatments include migraine-specific medications, such as triptans; nonopiate based analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs); opiate-based analgesics; and numerous over-the counter medications.4 Preventive treatments such as β-blockers, antidepressants, anti-epileptics, and onabotulinumtoxinA are FDA-approved for prevention of migraine, but can have limited effectiveness, intolerable adverse effects, and restricted or conditional coverage.5 Other medications under investigation include calcitonin gene-related peptide (CGRP) antibodies, erenumab and fremanezumab.6,7

Approximately 40% of migraine sufferers remain undiagnosed. Among those diagnosed, 25% are cared for by neurologists or headache specialists, 10% of whom are dissatisfied with the acute and preventive treatment options.8-11 Migraine is associated with symptoms of depression, anxiety disorder, and irritable bowel syndrome, among others. These symptoms increase healthcare utilization and overall costs.12-14 Patients with a combination of the moderate-to-high frequency of headache days, high propensity for comorbidities, and high healthcare utilization, constitute a subgroup of high-demand patients with migraine. A study showed migraine patients cost approximately $10,000 annually.13 Migraine, particularly in high-demand patients with migraine, also affect work, productivity, and daily functioning.12-14 The current disease and treatment landscape for migraine represents a high unmet need for these patients.10

The recent FDA approval for gammaCore using acute treatment of migraine was based on a randomized, sham-controlled prospective study of nVNS for the acute treatment of migraine (PRESTO) study. It demonstrated superiority of gammaCore adjunct to standard of care (SOC) over sham with SOC.3,15 The cost-effectiveness of gammaCore compared to SOC is documented and shown to be dominant (ie, gammaCore was more effective while costing less, [United States and Germany] and cost-effective [United Kingdom] for cluster headache).16-18 The cost-effectiveness of gammaCore for migraine treatment remains unknown and needs to be characterized. We performed a cost-effectiveness analyses of gammaCore adjunct to SOC for migraine compared to SOC alone and assessed the cost-effectiveness of treatment sequence strategies.

Methods

We developed 2 models: 1 for the treatment comparison of gammaCore plus SOC versus SOC alone, and 1 for treatment sequence strategy comparisons of starting with gammaCore for acute treatment and providing erenumab prevention for failures; starting with SOC acute treatment and providing erenumab prevention for failures; and starting with and providing erenumab prevention without prior treatment with acute treatment with either gammaCore or SOC. The cost-effectiveness analyses were designed and implemented in accordance to current methodological guidelines.19 The main sources of primary data were the PRESTO trial, supported by additional evidence and insights from Strickland et al and Polson et al.15,20 The treatment protocol for PRESTO was 3 two-minute stimulations followed by a 3-minute break and, if pain persisted, another 3 two-minute stimulations (3-3-3 protocol).21 PRESTO was reviewed and approved by a relevant ethics committee and details of the trial have been previously published.20

Model Structure

The model approach and structure were based on treatment of acute attacks to yield 3 potential outcomes–failures, partial responders, and persistent responders.22,23 Failures were those patients who experienced lack of adherence or lack of efficacy, and the proportion of responses to treated attacks (no pain within 30 minutes with no use for rescue medications) was 0%. GammaCore patients who failed were immediately identified using 1 or 2-month prescriptions with no further refills. Partial responders are patients who experienced partial efficacy, with the proportion of responses to treated attacks between 1% and 50%. These patients could be retrained to yield additional responders, additional failures, or remain as partial responders. Responders were patients who met the equivalent of PRESTO trial outcomes. The proportion of responses to attacks ≥50% (pain free) did not need other medication. Individuals in each outcome could remain in the same outcome group. In addition, failures could be offered erenumab. The model structure is shown in Figure 2. The decision tree model parameters were populated with data from the PRESTO trial providing the base case parameters.15 Cost data were derived from Polson et al and economic considerations driven by data from Strickland et al.20,23 Additional insights, including event rates for erenumab, were drawn from literature.6,24 The models were designed from a payer perspective with a time horizon of 1 year and built using Tree Age Pro–Healthcare (2018 R1, Williamsburg, MA). Uncertainty was incorporated by using distributions around parameter estimates for treatment effects, costs, and utilities. In addition, 100,000 trials (Monte Carlo simulations) were performed to yield a mean estimate of costs, effectiveness, and incremental cost-effectiveness ratio (ICER). A range of sensitivity analyses were also performed to evaluate the robustness of the model and test the impact of modifying parameter estimates on the models output. The decision trees are shown in Figures 3a and 3b.

Model Design and Parameter Estimates

Primary Model Considerations

The probability of failing treatment within 1-month is prob_Fail1M. The probability of responders who benefit adequately (≥50% pain-free response) from gammaCore and will reduce the need for other medications is prob_Resp_gammaCore while the probability of being a responder in the SOC arm is prob_Resp_SOC. The probability of partial-responders that may benefit and continue to use gammaCore is prob_NonRespResp and to still fail after retraining is prob_NonRespNon. The impact of consistent success of gammaCore treatment reduces the costs of care for migraine patient is reduction_Factor. The number of monthly gammaCore prescriptions per patient for a 12-month period is months_Prescription, the cost per prescription to payers is cost_gammaCore, (rounded up from average wholesale price (AWP) at minus 15%). The overall annual cost of care for the target migraine patient population based on current SOC is cost_SOC_Care. Utility estimates were derived from Strickland et al based on EQ-5D index measurements for failures, partial responders, and responders. Model assumptions were based on insights from the literature.6,23-25

Secondary Treatment Sequence Model Considerations

The annual cost of erenumab plus administration is cost_Erenumab_Annual, the probability of response while on erenumab is prob_Resp_Erenumab, and the utility for patients on erenumab group is utility_Erenumab. Parameter definitions and base case and corresponding sensitivity analyses estimates are shown in Table 1.6,15,20,23

Model Outputs

The model outputs were ICERs for cost per QALY. These were derived from the difference in overall costs between gammaCore plus SOC (CgammaCore) and SOC alone (CSoC), and then divided by the difference in effectiveness, and QALY between gammaCore plus SOC (EgammaCore) and SOC alone (ESoC). The approach was similar for the secondary model. We compared gammaCore-based sequences to corresponding SOC-based and non-prerequisite sequences, as well as corresponding erenumab-based sequences. A series of 1-way deterministic sensitivity analyses were performed for high and low values shown in Table 1. Additional probabilistic sensitivity analyses were performed.

Results

ICER

gammaCore plus SOC arm versus SOC alone

The annual mean costs for gammaCore plus SOC arm (CgammaCore) was $9543, and for SOC alone (CSoC) was $10,010. The mean QALYs for gammaCore plus SOC arm (EgammaCore) was 0.67 and for SOC alone arm (ESoC) was 0.63. Thus, gammaCore plus SOC arm was dominant (ie, was more effective but cost less) over SOC alone. See Table 2.

Sequencing Strategy Options

The annual mean costs and QALYs for gammaCore followed by erenumab were $10,678 and 0.70, respectively, while the annual mean costs and QALYs for SOC followed by erenumab were $11,583 and 0.67, respectively. The mean costs and QALYs for initiating erenumab with no prior gammaCore or SOC treatment were $13,766 and 0.65, respectively. GammaCore followed by erenumab for failing patients was dominant over all other strategies, as shown in Table 3.

Sensitivity Analyses

 
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