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Supplements Economic Considerations in Cluster Headache and Non-Invasive Vagus Nerve Stimulation
Real-World Health Plan Claims Analysis of Differences in Healthcare Utilization and Total Cost in Patients Suffering From Cluster Headaches and Those Without Headache-Related Conditions
Michael Polson, MS, PharmD; Todd C. Lord, PharmD; Themmi M. Evangelatos, PharmD, MSBA; Maria Lopes, MD; and Briana L. Santaniello, PharmD, MBA
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Cost-Effectiveness of gammaCore (Non-Invasive Vagus Nerve Stimulation) for Acute Treatment of Episodic Cluster Headache
Mkaya Mwamburi, MD, PhD, MA (Econ); Eric J. Liebler, BA; and Andrew T. Tenaglia, BA

Cost-Effectiveness of gammaCore (Non-Invasive Vagus Nerve Stimulation) for Acute Treatment of Episodic Cluster Headache

Mkaya Mwamburi, MD, PhD, MA (Econ); Eric J. Liebler, BA; and Andrew T. Tenaglia, BA
Cluster headache is a debilitating disease characterized by excruciatingly painful attacks that affects 0.15% to 0.4% of the US population. Episodic cluster headache manifests as circadian and circannual seasonal bouts of attacks, each lasting 15 to 180 minutes, with periods of remission. In chronic cluster headache, the attacks occur throughout the year with no periods of remission. While existing treatments are effective for some patients, many patients continue to suffer. There are only 2 FDA-approved medications for episodic cluster headache in the United States, while others, such as high-flow oxygen, are used off-label. Episodic cluster headache is associated with comorbidities and affects work, productivity, and daily functioning. The economic burden of episodic cluster headache is considerable, costing more than twice that of nonheadache patients. gammaCore adjunct to standard of care (SoC) was found to have superior efficacy in treatment of acute episodic cluster headaches compared with sham-gammaCore used with SoC in ACT1 and ACT2 trials. However, the economic impact has not been characterized for this indication. We conducted a cost-effectiveness analysis of gammaCore adjunct to SoC compared with SoC alone for the treatment of acute pain associated with episodic cluster headache attacks. The model structure was based on treatment of acute attacks with 3 outcomes: failures, nonresponders, and responders. The time horizon of the model is 1 year using a payer perspective with uncertainty incorporated. Parameter inputs were derived from primary data from the randomized controlled trials for gammaCore. The mean annual costs associated with the gammaCore-plus-SoC arm was $9510, and mean costs for the SoC-alone arm was $10,040. The mean quality-adjusted life years for gammaCore-plus-SoC arm were 0.83, and for the SoC-alone arm, they were 0.74. The gammaCore-plus-SoC arm was dominant over SoC alone. All 1-way and multiway sensitivity analyses were cost-effective using a threshold of $20,000. gammaCore dominance, representing savings, was driven by superior efficacy, improvement in quality of life (QoL), and reduction in costs associated with successful and consistent abortion of episodic attacks. These findings serve as additional economic evidence to support coverage for gammaCore. Additional real-world data are needed to characterize the long-term impact of gammaCore on comorbidities, utilization, QoL, daily functioning, productivity, and social engagement of these patients, and for other indications.
Am J Manag Care. 2017;23:-S0
For author information and disclosures, see end of text.
 
Cluster headache, a trigeminal autonomic cephalalgia, is a debilitating disease (also called “suicide headache”) that is characterized by severely intense attacks that are excruciatingly painful.1-5 Episodic cluster headache, which accounts for 80% to 90% of cluster headache patients, manifests as seasonal bouts of attacks, each lasting between 1 and 8 weeks, occurring in circadian, circannual pattern in the spring and in the fall months with periods of remission.6,7 In contrast, chronic cluster headache refers to when the attacks occur throughout the 12 months with periods of remission of less than 1 month. Episodic cluster headache affects approximately 300,000 adults in the United States.1 There are few treatments available, and then only with limited effectiveness for aborting acute attacks of episodic cluster headache. There are only 2 medications approved by the FDA, subcutaneous sumatriptan and sublingual ergotamine tartrate. All other forms of treatment are used off-label. The disease and treatment landscapes represent a high unmet need, with the FDA providing fast-track status for expedited review to experimental agent galcanezumab for cluster headache prevention.8 The illness is difficult to diagnose correctly, and there are typically extensive delays between onset of symptoms and the correct diagnosis.9 Nearly 3 out of 5 patients are diagnosed at least 3 years after onset of symptoms, while 22% of patients are diagnosed after at least 10 years.6 Episodic cluster headache is also associated with numerous comorbidities, including depression, anxiety disorder with suicide ideation, and an increased need for medications and health utilization.6,7,10 Episodic cluster headache also affects work, productivity, daily functioning, and travel abilities for those patients with the condition. The economic burden of episodic cluster headache is considerable. In 1 study based on claims data, episodic cluster headache patients cost more than twice that of nonheadache patients.10

gammaCore (non-invasive vagus nerve stimulator; electroCore, Basking Ridge, NJ) has recently been cleared by the FDA for the treatment of pain associated with episodic cluster headaches in the United States.11 Recent randomized, sham-controlled trials (ACT1 and ACT2) demonstrated clinically significant superiority of gammaCore adjunct to standard of care (SoC) over sham-gammaCore with SoC among patients treated for episodic cluster headaches; it did so by significantly reducing cluster headache attack intensity within 15 minutes of initiating treatment and eliminating the need for rescue medication.12-14 In addition, gammaCore is practical, as it is hand-held, portable, and easy-to-use. The device is safe with no associated toxicity, drug interactions, or serious device-related adverse events (AEs). Successful treatment with gammaCore has been associated with reduced consultations and referrals in primary headaches.15 The clinical impact of gammaCore is well documented, and for many patients in whom gammaCore works effectively, treatment with gammaCore represents a life-changing experience.16 Other cost-effectiveness analyses of gammaCore compared with SoC have shown gammaCore to be dominant (German payer perspective) and cost-effective (United Kingdom payer perspective) as a prophylactic treatment of chronic cluster headache.17,18 However, the economic impact and cost-effectiveness of gammaCore as an effective treatment of acute attacks of episodic cluster headache remains to be determined and characterized. We designed and performed a cost-effectiveness analysis comparing gammaCore adjunctive to SoC with SoC alone, for the acute treatment of episodic cluster headache.

Methods

We conducted a cost-effectiveness analysis of gammaCore adjunct to SoC compared with SoC alone for the treatment of acute pain associated with episodic cluster headache attacks in accordance with current guidelines.19 The main sources of primary data were the ACT trials, supported by additional evidence and insights from Polson et al, Choong et al, Nesbitt et al, and Rozen et al.6,7,10,12,14,16 Both ACT1 (ClinicalTrials.gov identifier: NCT01792817) and ACT2 (ClinicalTrials.gov identifier: NCT01958125) were sham-controlled, double-blind, randomized trials comparing gammaCore adjunct with SoC to SoC alone. Both multicenter trials were reviewed and approved by relevant ethics committees. A meta-analysis of the 2 trials was conducted and also previously presented.12 The treatment protocol for ACT1 was three 2-minute stimulations, each separated by 1 minute, delivered on the right side of the neck. Patients could use gammaCore twice daily.14 The treatment protocol for ACT2 was three 2-minute stimulations followed by a 3-minute break, and if pain persisted, another three 2-minute stimulations would be delievered  on the ipsilateral side of the cluster attack (3-3-3 protocol). Patients could use gammaCore up to 4 times in 1 day.13 Details of both trials have been previously published.13,14

Model Structure

The model structure was based on treatment of acute attacks to yield 3 outcomes: failures, nonresponders, and responders. Failures were those patients who experienced lack of adherence or lack of efficacy, and the proportion of responses to treated attacks (no pain within 15 minutes with no use for rescue medications) was 0%. Nonresponders are patients who experienced partial efficacy with the proportion of responses to treated attacks between 1% and 50%. These patients also benefited from the gammaCore treatment by reduction in duration or intensity of treated attack, or both, but gammaCore did not necessarily prevent the use of rescue medications. These patients could be retrained to yield additional responders or additional failures, or to remain as partial responders. Responders were patients who met the equivalent of the trial outcomes of ACT1 and ACT2: The proportion of responses to attacks was ≥50%. Individuals in each outcome may remain in the same outcome group. The model structure is shown in Figure 1.

The model was designed to compare patients treated with gammaCore adjunct to SoC versus SoC alone using a decision tree. The decision-tree model parameters were populated with data from pooled analysis of the 2 ACT trials with data from the meta-analysis providing the base case parameters.12 For clinical outcomes, findings from ACT1 and ACT2 provided lower and upper limits respectively for estimates for sensitivity analyses.13,14 Cost data were derived from Polson et al and epidemiological considerations were driven by data from Rozen et al.7,10 Additional insights were drawn from the literature.3-6,15,16 The model is designed from a payer perspective with a time horizon of 1 year. The model was designed and built using TreeAge Pro Healthcare, v2017.R1 (TreeAge Software; Williamstown, Massachusetts). Uncertainty was incorporated by using distributions around parameter estimates for treatment effects, costs, and utilities. In addition, 100,000 trials or iterations (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 tree is shown in Figure 2.

Model Design and Parameter Estimates

Patients who fail to respond to gammaCore do so within the duration covered by the first device. Therefore, failures would not need prescriptions for additional devices, would not have changes in utilities from baseline, and the costs associated with their care would remain the same as for patients in SoC; ie, there is no benefit conferred to them for receiving the 1 month’s worth of gammaCore treatment for which they did not respond. The base case probability of failing treatment within 1 month is 0.2 (prob_Fail1M). Those who do not fail within 1 month may be responders or nonresponders in the gammaCore arm. Responders are those who benefit adequately from gammaCore and will not need rescue medications for the attacks to which they respond. The effective probabilities of being a responder in the gammaCore arm and the SoC-alone arm are 0.42 (prob_Resp_gammaCore) and 0.15 (prob_Resp_SoC), respectively. Nonresponders partially benefit from using gammaCore, may return to the provider, and may be retrained to achieve better performance from gammaCore. A proportion of nonresponders who may respond favorably enough for them to continue to use gammaCore, even if using for partial benefit, is 0.50 (prob_NonRespResp). This assumption is based on insights from the literature and patient experiences.3,4,7,10,12-16,18,20-22 Others, even after retraining, may not benefit further and will stop using gammaCore by the second device. The probability among nonresponders is also 0.50 (prob_NonRespNon). The impact of consistent success of gammaCore treatment is a reduction in costs of care for episodic cluster headache patients by 50% (reduction_Factor). For a 12-month period, the base case average number of gammaCore prescriptions per patient is 6 (months_Prescription). While the more realistic average number of prescriptions annually may be closer to 4, a more conservative analysis using 6 was used.

The cost per prescription to payers (cost_gammaCore) will be $590 (rounded up from average wholesale price [AWP] minus 15%). For nonresponders in the gammaCore arm who undergo retraining, the associated cost that may be charged by doctors is $100 (cost_Training). The overall annual cost of care for episodic cluster headache patients based on current SoC (Polson et al) was $24,820 for 3 years = $8270/year in 2013 US$.10 Based on appreciating costs at 5% inflation annually, the per-year medical cost in 2017 US$ would be $10,040 ± $490 (cost_SoC_Care). Utility estimates were derived from the ACT2 trial data based on EQ-5D health index measurements. We used utilities averaged by treatment group for the gammaCore-plus-SOC arm of 0.82 ± 0.046 (utility_gammaCore) and for the SoC-alone arm of 0.72 ± 0.046 (utility_SoC) as the base case. Utilities averaged by response—responders, 0.90 ± 0.048 (utility_Resp); nonresponders, 0.71 ± 0.038 (utility_NonResp); failures, 0.71 ± 0.038 (utility_NonResp)—were used for sensitivity analyses. Parameter definitions and estimates are shown in Table 1. The model output was ICER for cost per quality-adjusted life year (QALY), derived as the ratio between marginal costs (the difference in costs associated with gammaCore plus SoC minus costs associated with SoC alone) and marginal effectiveness (the difference in effectiveness ie, QALYs associated with gammaCore plus SoC minus QALYs associated with SoC alone) [(CgammaCore  - CSoC) /(EgammaCore  - ESoC)].

 
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