Clinical benefits and economic cost-savings of remote electrical neuromodulation (REN) for migraine prevention.

AIMS: Assess the clinical benefits and associated direct and indirect cost-savings from Remote Electrical Neuromodulation (REN) for migraine prevention. METHODS: REN, a prescribed, wearable, FDA-cleared neuromodulation-device for acute and/or preventive treatment of migraine, recently demonstrated efficacy for migraine prevention when used every-other-day, in a prospective, randomized, double-blind, placebo-controlled, multi-center study. Following baseline (4-weeks), subjects underwent treatment with REN or placebo (8-weeks), and electronically reported migraine symptoms and acute treatments daily. Therapeutic-gain was the between-groups difference (REN minus placebo) in change from baseline to the second month of intervention. Health-economics impact was derived as cost-savings associated with REN's clinical benefits. RESULTS: Out of 248 subjects randomized (128 active, 120 placebo), 179 (95:84) qualified for modified intention-to-treat (mITT) analysis. Significant therapeutic gains favoring REN vs. placebo were found (Tepper et al. 2023), including mean (±SD) reduction in number of acute medication days (3.5 ± 0.4 vs. 1.2 ± 0.5; gain = 2.2; p = .001) and presenteeism days (2.7 ± 0.3 vs. 1.1 ± 0.4; gain = 1.6, p = .001). Mean changes of provider visits (reduction of 0.09 ± 0.1 vs. increase of 0.08 ± 0.2; p = .297), and reduction of absenteeism days (0.07 ± 0.1 vs. 0.07 ± 0.2; p = .997) were not significant. Mean annual cost-saving for one patient using REN for migraine prevention estimated $10,000 (±$1,777) from reductions in these four clinical outcomes relative to baseline without REN treatment. Extrapolated to a hypothetical US commercial health-plan of one-million covered lives, assuming the national prevalence of migraine patients on preventive treatment, annual mean (±SE) cost-saving from using REN migraine prevention estimated $560.0 million (±$99.5 million) from reduction in direct (∼$330 millionm) and indirect costs (∼$230 millionm) measured. LIMITATIONS: Clinical and cost-savings benefits presented are conservative, assessed only from endpoints measured in the clinical trial. Moreover, some of the endpoints had only scarce or no occurrences during the study period. CONCLUSIONS: Coverage of the REN-device for migraine prevention may significantly reduce disease-burden and save a one-million-member payer plan at least $560 million per year.

Migraine affects more than 1 billion people worldwide, causing significant disability and substantial clinical economic burden. Remote Electrical Neuromodulation (REN) is a prescribed, wearable, non-pharmacological, non-invasive device (Nerivio), indicated for acute and/or preventive treatment of migraine with or without aura in patients 12 years and older. Efficacy of REN for migraine prevention was recently demonstrated in a randomized, blinded, placebo-controlled clinical-trial. This study further analyzes clinical benefits from endpoints measured in the clinical-trial as well as their associated direct and indirect costs. Out of 248 subjects randomized (128 active, 120 placebo), 179 (95:84) qualified for modified intention-to-treat (mITT) analysis. Significant therapeutic gains favoring REN over placebo were found, including an average reduction of 3.4 acute medication days/month, and an average reduction of 2.7 presenteeism days/month. A reduction in the number of provider visits and absenteeism days was also reported, though not significantly differed from changes in the control group. Mean annual cost-saving from reductions in these four clinical outcomes relative to baseline without REN treatment for a patient using REN for migraine prevention estimated $10,000. Extrapolated to a hypothetical US commercial health-plan of one million covered lives, annual mean cost-saving from using REN for migraine prevention is estimated to be $560.0 million, composed of $327.8 million direct costs and $232.2 million indirect costs. Thus, REN preventive treatment for migraine reduces disease burden and leads to meaningful cost-saving, both direct and indirect, proposing clinical and financial incentives for patients, health insurance systems, and employers to utilize REN for migraine prevention.

Patient-Centered Treatment of Chronic Migraine With Medication Overuse: A Prospective, Randomized, Pragmatic Clinical Trial.

BACKGROUND AND OBJECTIVES: Overuse of symptomatic (i.e., acute) medications is common among those with chronic migraine. It is associated with developing frequent headaches, medication side effects, and reduced quality of life. The optimal treatment strategy for patients who have chronic migraine with medication overuse (CMMO) has long been debated. The study objective was to determine whether migraine preventive therapy without switching or limiting the frequency of the overused medication was noninferior to migraine preventive therapy with switching from the overused medication to an alternative medication that could be used on ≤2 d/wk. METHODS: The Medication Overuse Treatment Strategy (MOTS) trial was an open-label, pragmatic clinical trial, randomizing adult participants 1:1 to migraine preventive medication and (1) switching from the overused medication to an alternative used ≤2 d/wk or (2) continuation of the overused medication with no maximum limit. Participants were enrolled between February 2017 and December 2020 from 34 clinics in the United States, including headache specialty, general neurology, and primary care clinics. The primary outcome was moderate to severe headache day frequency during weeks 9 to 12 and subsequently during weeks 1 to 2 after randomization. RESULTS: Seven hundred twenty participants were randomized; average age was 44 (SD 13) years; and 87.5% were female. At baseline, participants averaged 22.5 (SD 5.1) headache days over 4 weeks, including 12.8 (SD 6.7) moderate to severe headache days and 21.4 (SD 5.8) days of symptomatic medication use. Migraine preventive medication without switching of the overused medication was not inferior to preventive medication with switching for moderate to severe headache day frequency during weeks 9 to 12 (switching 9.3 [SD 7.2] vs no switching 9.1 [SD 6.8]; p = 0.75, 95% CI -1.0 to 1.3). The treatment strategies also provided similar outcomes during the first 2 weeks (switching 6.6 [SD 3.7] moderate to severe headaches days vs no switching 6.4 [SD 3.6]; p = 0.57, 95% CI -0.4 to 0.7). DISCUSSION: When reduction in moderate to severe headache days was used as the outcome of interest for the management of CMMO, migraine preventive medication without switching or limiting symptomatic medication is not inferior to migraine preventive medication with switching to a different symptomatic medication with a maximum limit of 2 treatment days per week. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier NCT02764320. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, for patients who have CMMO, migraine preventive medication without switching or limiting the overused medication is noninferior to migraine preventive medication with switching and limiting symptomatic medication.

Ubrogepant for the Acute Treatment of Migraine: Pooled Efficacy, Safety, and Tolerability From the ACHIEVE I and ACHIEVE II Phase 3 Randomized Trials.

INTRODUCTION: Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. The efficacy and safety of ubrogepant were demonstrated in two pivotal phase 3, single-attack, randomized, placebo-controlled trials (ACHIEVE I and ACHIEVE II). METHODS: We conducted a post hoc analysis of pooled data from the ACHIEVE trials to evaluate the efficacy, safety, and tolerability of ubrogepant 50 mg (the only dose evaluated in both trials) versus placebo across a large population of participants with migraine. The coprimary efficacy outcomes were pain freedom and absence of the most bothersome migraine-associated symptom (including photophobia, phonophobia, and nausea) at 2 h post dose. Secondary outcomes included pain relief at 2 h post dose, sustained pain relief and pain freedom from 2 to 24 h, and absence of specific migraine-associated symptoms at 2 h post dose. RESULTS: A total of 2240 eligible participants were randomized to placebo (n = 1122) or ubrogepant 50 mg (n = 1118) in the ACHIEVE trials. Pain freedom at 2 h was reported in 13.0% of participants in the pooled placebo group and 20.5% in the pooled ubrogepant 50 mg group (odds ratio [OR] 1.72; 95% confidence interval [CI] 1.34, 2.22; P < 0.001). Absence of the most bothersome migraine-associated symptom at 2 h was reported by 27.6% in the pooled placebo group and by 38.7% in the pooled ubrogepant 50 mg group (OR 1.68; 95% CI 1.37, 2.05; P < 0.001). Adverse events (AEs) within 48 h after the initial or optional second dose were reported by 11.5 and 11.2% of participants in the pooled placebo and pooled ubrogepant 50 mg groups, respectively. The most common AE was nausea (1.8 and 1.9%, respectively). No serious AEs related to treatment or discontinuations due to AEs were reported. CONCLUSION: These results further support the efficacy, safety, and tolerability of ubrogepant for the acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: ACHIEVE I: NCT02828020; ACHIEVE II: NCT02867709.

Headache characteristics and burden from chronic migraine with medication overuse headache: Cross-sectional observations from the Medication Overuse Treatment Strategy trial.

OBJECTIVE: To describe headache characteristics, medication use, disability, and quality of life in a large patient cohort from the United States who have chronic migraine (CM) and medication overuse headache (MOH). METHODS: In all, 610 adult patients were enrolled into the Medication Overuse Treatment Strategy trial from 34 healthcare clinics, including headache specialty, general neurology, and primary care clinics. Descriptive statistics characterize baseline demographics, headache characteristics, medication use, disability (Headache Impact Test 6 [HIT-6] and Migraine Functional Impact Questionnaire [MFIQ]), pain interference (PROMIS Pain Interference), and quality of life (EQ-5D-5L). Relationships with headache frequency were assessed. RESULTS: Mean age was 45 years (SD 13) and 531/608 (87.3%) were females. Mean headache days per 30 was 24.3 (SD 5.5), including 13.6 (SD 7.1) with moderate to severe headache. Daily headaches were reported by 36.1% (219/607) of patients. Acute headache medications were used on 21.5 (SD 7.5) per 30 days. The most commonly overused medications were simple analgesics (378/607, 62% of patients), combination analgesics (246/607, 41%), and triptans (128/607, 21%). HIT-6, MFIQ, PROMIS Pain Interference, and EQ-5D-5L scores demonstrated substantial negative impact from CM with MOH on patient functioning and quality of life. Higher headache frequency was associated with more moderate-severe headache days, more frequent acute headache medication use, greater headache-related disability, and lower quality of life. Only 272/606 (44.9%) were taking migraine preventive medication. CONCLUSIONS: CM with MOH is associated with a large burden on patients in the United States. Higher headache frequency is associated with greater impact on functioning, pain interference, and quality of life.

The emerging role of gammaCore® in the management of cluster headache: expert panel recommendations.

A panel of 9 experts, including neurologists, other headache specialists, and medical and pharmacy directors, from 4 health plans (1 integrated delivery network and 3 plans with commercial, Medicare, and Medicaid lines of business), convened to discuss cluster headache (CH). Topics covered included the current treatment landscape, treatment challenges, economic impact of disease, and gaps in care for patients with CH. One major challenge in the management of CH is that it is underrecognized and frequently misdiagnosed, leading to delays in and suboptimal treatment for patients who suffer from this painful and disabling condition. The management of CH is challenging due to the lack of a robust evidence base for preventive treatment, the adverse events (AEs) associated with conventional preventive treatments, the variability of response to acute treatments, and the challenging reimbursement landscape for well-accepted treatments (eg, oxygen). The lack of effective prevention for many patients may lead to the excessive use of acute therapies, often multiple times each day, which drives the cost of illness up significantly. The goal of the panel discussion was to discuss the role of gammaCore, the recently released first non-invasive vagus nerve stimulation (nVNS) therapy in the acute treatment of patients with episodic CH (eCH), in the management of CH. The panel reviewed current practices and formulated recommendations on incorporating a newly released therapy into CH management. The panel explored the role of traditional management strategies as well as that of gammaCore in the acute treatment of patients with eCH. Resources that may be useful in the treatment of patients with CH were also discussed.