Disutility of Cognitive Processing Speed (CPS) Impairment in the Context of Multiple Sclerosis: A Time Trade-Off (TTO) Elicitation Study.

Introduction: Cognitive impairment, especially relating to cognitive processing speed, is a major cause of disability in people with multiple sclerosis (MS). Utility values are quantitative estimates of the quality of life experienced in specific health states and are a key component of cost-effectiveness modelling. However, existing health state utility values in MS typically focus on physical ability and are generally derived using generic (not disease-specific) measures of quality of life. The objective of the current study was to generate health state utility values for levels of cognitive impairment. We used a direct utility elicitation approach called the time trade-off (TTO) methodology. Materials and Methods: Health state descriptions were created following interviews with healthcare professionals, patients, and caregivers in the United States (n=35), and with healthcare professionals in the UK (n=5). Three health states (mild, moderate, and severe impairment) were defined based upon a well-established and validated test for cognitive dysfunction called the Symbol Digit Modalities Test (SDMT) and described using qualitative interview findings. Next, interviews with members of the general public in the UK were conducted to estimate utility values for each health state using the TTO methodology. The procedure was based on the established Measurement and Valuation of Health (MVH) protocol, which generates values on a scale from 0.0 to 1.0. Results: Mean health state utility values were 0.77 ± 0.24 in "mild impairment" (SDMT 43-40), 0.57 ± 0.26 in "moderate impairment" (SDMT 39-32), and 0.34 ± 0.28 in "severe impairment" (SDMT ≤ 31). Discussion: Results indicate that the public perceives that health states of cognitive slowing (as observed in MS) are associated with a substantial reduction in affected individuals' health-related quality of life, quantified using the TTO methodology. Future economic modeling should consider how utility impacts of both cognitive and physical disability can be appropriately incorporated.

Healthcare costs and resource utilization in patients with migraine treated with erenumab: A retrospective, non-interventional study using claims data from the United States.

OBJECTIVE: To assess healthcare costs and healthcare resource utilization (HCRU) among adult patients who newly initiated erenumab in the United States. METHODS: This retrospective, non-interventional analysis included adult patients (aged ≥18 years) newly initiating erenumab and who had three consecutive monthly claims for erenumab (11/1/2017-9/1/2019) from the Komodo Health database. Outcomes included migraine-related and all-cause costs, use of other preventive/acute migraine medications, and HCRU. All outcomes were compared during the 180-day pre- versus the 180-day post-index periods. Cost outcomes were also assessed for longer periods including post-index Days 91-270 and monthly mean post-index costs for the longest time of continuous insurance enrollment. RESULTS: Overall, 1839 patients with migraine were included for analysis. Compared to the 180-day pre-index period, an increase in total migraine-related costs (+$2639; p < 0.0001), migraine-related prescription costs (+$3435, p < 0.0001), all-cause total costs (+$2977; p < 0.001), and all-cause prescription costs (+$4102; p < 0.0001) were observed during the 180-day post-index period after adjusting for covariates. Conversely, reduction in migraine-related medical costs (-$896; p < 0.0001), and significantly lower odds of migraine-related emergency room visits (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.44-0.82; p = 0.001), migraine-related office visits (OR 0.58, 95% CI 0.53-0.64; p < 0.0001), and migraine-related neurologist visits (OR 0.69, 95% CI 0.63-0.75; p < 0.0001) were observed during the 180-days post-index period. There were significant decreases in the odds of having overall preventive migraine medications (OR 0.81, 95% CI 0.75-0.87; p < 0.0001), acute-migraine medications (OR 0.92, 95% CI 0.85-1.00; p = 0.038), and triptan (OR 0.79, 95% CI 0.73-0.85; p < 0.0001) during the 180-day post-index period. Sensitivity analyses on cost outcomes found no statistically significant differences in pre-index migraine-related costs compared to post-index migraine-related costs when assessing longer post-index follow-up periods. CONCLUSION: Initiation of therapy with a novel treatment is often associated with an increase in overall healthcare costs due to the entrance costs associated with novel therapy. For a chronic condition such as migraine, cost versus health benefits should be evaluated over a long period (e.g., ≥2 years) to better understand the true benefits of therapy. Data from this study suggest that the entrance cost for erenumab, the primary driver of the high post-index prescription costs gets mitigated by reduced medical costs over long-term follow-up. The results indicate better disease management in adult patients with migraine, which should be an important consideration for both patients and payors, as these findings have shown an offset between migraine-related prescription and medical costs.

Do clinical trials prepare to fail by failing to prepare? An examination of MS trials and recommendations for patient-reported outcome measure selection.

BACKGROUND: Many clinical trials use patient-reported outcome (PRO) measures, which can influence treatment decision-making, drug approval and label claims. Given that many PRO measure options exist, and there are conceptual and contextual complexities with PRO measurement, we aimed to evaluate how and why specific PRO measures have been selected for pivotal multiple sclerosis (MS) clinical trials. Specifically, we aimed to identify the reasons documented for PRO measure selection in contemporary phase III MS disease-modifying treatment (DMT) clinical trials. METHODS: We searched for phase III clinical trials of MS DMTs published between 2015 and 2021 and evaluated trial protocols, or primary publications where available, for PRO measure selection information. Specifically, we examined study documents for their clarification of clinical concepts measured, definitions of concepts measured, explanations of which PRO measures were considered, why specific PRO measures were chosen, and trade-offs in PRO measure selection. RESULTS: We identified 1705 abstracts containing 61 unique phase III MS DMT clinical trials. We obtained and examined 27/61 trial protocols. Six protocols were excluded: four contained no mention of PRO measures and two contained redacted sections preventing adequate assessment, leaving 21 protocols for assessment. For the remaining 34 trials (61-27), we retrieved 31 primary publications; 15 primary publications mentioned the use of a PRO measure. None of the 36 clinical trials that mentioned the use of PRO measures (21 protocols and 15 primary publications) documented clear PRO or clinical outcome assessment (COA) measurement strategies, provided clear justifications for PRO selection, or reasons why specific PRO measures were selected when alternatives existed. CONCLUSION: PRO measure selection for clinical trials is not evidence-based or underpinned by structured systematic approaches. This represents a critical area for study design improvement as PRO measure results directly affect patient care, PRO measurement has conceptual and contextual complexities, and there is a wide range of options when selecting a PRO measure. We recommend trial designers use formal approaches for PRO measure selection to ensure PRO measurement-based decisions are optimised. We provide a simple, logical, five-stage approach for PRO measure selection in clinical trials.

Real-world treatment satisfaction with erenumab in migraine: analysis of the US National Health and Wellness Survey.

OBJECTIVE: The treatment landscape for the prevention of migraine has rapidly evolved in recent years with the advent of calcitonin gene-related peptide therapy, including erenumab. The objective of this study was to assess patient-reported treatment satisfaction among erenumab users. METHODS: This retrospective, cross-sectional study used data from the 2019 US National Health and Wellness Survey collected during March-July 2019. Respondents self-reporting physician-diagnosed migraine and currently using erenumab were analyzed. Treatment satisfaction was measured on a seven-point Likert scale. Data were further reported by the duration of erenumab treatment. Data on respondents' socio-demographic characteristics and treatment patterns were also collected. RESULTS: Overall, 67 respondents using erenumab with or without other migraine preventives for up to 1 year were included in the analysis. The mean (standard deviation) age was 46.7 (12.9) years. Most of the respondents were women (86.6%), White (74.6%), and commercially-insured (67.2%). Notably, 40.3% had ≥1 comorbidity per the Charlson Comorbidity Index. Approximately half of the respondents were college graduates and employed (49.3% each). Among the 67 respondents, 46 received erenumab exclusively. Across both cohorts, the percentage of respondents who were satisfied with erenumab treatment was slightly higher among those with a longer treatment duration (overall erenumab cohort: 63.6%, 69.6%, and 75.8% for 0-<3, 3-<6, and 6-12 months, respectively; erenumab monotherapy cohort: 62.5%, 71.4%, and 87.5% for 0-<3, 3-<6, and 6-12 months, respectively). Treatment patterns before switching to erenumab revealed that most respondents had used ≥1 preventive treatment for migraine (80.6%; 54/67), over two-thirds (33/54) of whom had ≥2 treatment failures owing to nonresponse. CONCLUSION: Satisfaction was high among long-term erenumab users, indicating that those using erenumab for a longer duration are more satisfied. Furthermore, this study provided insights on the basic socio-demographics, disease characteristics, and health behaviors of erenumab users as well as their treatment patterns before switching to erenumab.

Assessment of the relative effectiveness of erenumab compared with onabotulinumtoxinA for the prevention of chronic migraine.

OBJECTIVE: To assess the available clinical and economic evidence of erenumab vs onabotulinumtoxinA for chronic migraine (CM) and present de-novo indirect treatment comparisons (ITCs) based on available clinical trial data. METHODS: We conducted ITCs based on results from the pivotal 295 trial (NCT02066415) of erenumab vs placebo and published aggregate data from the PREEMPT 1 (NCT00156910) and PREEMPT 2 (NCT00168428) trials of onabotulinumtoxinA vs placebo. ITCs were conducted for CM patients with and without prior administration of onabotulinumtoxinA and among CM patients with ≥3 prior preventive treatment failures. Efficacy was assessed based on responder rates of ≥50% reductions in monthly headache days (MHDs) and monthly migraine days (MMDs) as well as change from baseline in both MHDs and MMDs. RESULTS: Among patients with CM, 140 mg erenumab was associated with a reduction of 1.2 MHD (p = .092) and a reduction of 1.0 MMD (p = .174) compared to onabotulinumtoxinA at Week 12. Among onabotulinumtoxinA-naïve patients, erenumab was associated with a reduction of 1.8 MHD (p = .026) and 1.4 MMD (p = .080) at Week 12. Among patients that had received ≥3 prior preventive treatments, the odds ratios comparing erenumab vs onabotulinumtoxinA were 1.7 for ≥50% responder rates based on reductions in MHD (p = .155) and 1.7 for ≥50% responder rates based on reductions in MMD (p = .140). CONCLUSION: These findings suggest directional benefits (although not reaching the threshold of statistical significance) associated with erenumab vs onabotulinumtoxinA for the preventive treatment of CM. Evidence from this study may inform healthcare stakeholders in treatment selection and optimization for patients with CM.

Health Care Utilization and Costs in Patients With Migraine Who Have Failed Previous Preventive Treatments.

OBJECTIVE: To characterize health care utilization (HCU) and associated costs among patients with migraine categorized by the number of preventive treatment failures (TFs; 1 TF, 2 TFs, and 3+ TFs) using real-world data. METHODS: This retrospective analysis identified adults with incident migraine diagnosis in the IBM MarketScan Commercial and Medicare Supplemental database between January 1, 2011, and June 30, 2015. TF was defined in the 2 years after the first migraine diagnosis period. One TF, 2 TFs, and 3+ TFs were defined as patients who had received only 2 preventive treatments (PTs), 3 PTs, and 4+ PTs in the 2-year period, respectively. A negative binomial model was used to analyze HCU data, and a 2-part model was used for cost data controlling for the preindex Deyo-Charlson Comorbidity Index. RESULTS: Overall, 24,282 patients with incident migraine who had failed at least 1 PT were included in the analysis. Of these, 72.7% (n = 17,653) had 1 TF, 20.2% (n = 4,900) had 2 TFs, and 7.1% (n = 1,729) had 3+ TFs. Adjusted annualized rates of all-cause and migraine-specific HCU increased with an increase in the number of TFs (1.4-4 times higher; all p < 0.0001 vs 1 TF). The mean total all-cause health care costs were higher by $3,732 (95% confidence interval [CI]: $2,708-$4,588) in patients with 2 TFs and by $8,912 (95% CI: $7,141-$10,822) in patients with 3+ TFs vs those with 1 TF. Outpatient costs were the key drivers of differences in health care costs. CONCLUSIONS: TF in patients with migraine was associated with a substantial resource and cost burden, which increased with the number of TFs.

Real-world migraine-related healthcare resource utilization and costs associated with improved vs. worsened/stable migraine: a panel-based chart review in France, Germany, Italy, and Spain.

OBJECTIVE: To estimate the migraine-related healthcare resource utilization (HRU) and costs among patients with improved vs. worsened/stable migraine. METHODS: This was a follow-up to a retrospective, panel-based chart review conducted in France, Germany, Italy, and Spain among a panel of physicians (neurologists, headache specialists, and pain specialists) who agreed to participate in patient studies and had treated ≥10 migraine patients in 2017. Eligible physicians extracted data for up to five adults with ≥4 monthly migraine days (MMDs) who initiated a preventive treatment on or after 1 January 2013 and received physician care for ≥6 months after the date of the most recent preventive treatment initiation (index date). Based on the trajectory of migraine severity from the 1-month pre-index period to the 6-month post-index period, cohorts were classified as improved (converting from chronic to episodic or from chronic/episodic to <4 MMDs) or stable/worsened (remaining chronic/episodic or transforming from episodic to chronic) migraine. Migraine-related HRU and costs (2017 €) during the 6-month post-index period were compared between patients with improved vs. stable/worsened migraine. RESULTS: Overall, 470 patient charts were analyzed, with 339 classified as improved migraine and 131 classified as stable/worsened migraine. After adjusting for within-physician correlation, country, sex, and presence of comorbidities before the index date, the improved migraine cohort had significantly fewer migraine-related physician office visits (-0.81; p < .001), emergency room/accident & emergency (ER/A&E) visits (-0.67; p < .001), and hospitalizations (-0.12; p < .001) in the 6-month post-index period vs. the stable/worsened migraine cohort. Consistent with HRU patterns, the adjusted migraine-related costs for physician office visits (-€42.23; p < .05), hospitalizations (-€215.56; p < .05), and total costs (-€396.81; p < .01) in the 6-month post-index period were significantly reduced for the improved migraine cohort vs. the stable/worsened migraine cohort. CONCLUSIONS: Over a 6-month period following initiation of preventive migraine treatment, patients with improved migraine had significantly lower migraine-related HRU and costs than those with stable/worsened migraine.

Living with Burden of Migraine: The Analysis of "My Migraine Voice" Survey Results in Turkey.

INTRODUCTION: Migraine is a common, chronic neurologic disease which causes serious social and economical disability at both the individual and the community level. The aim of this study was to interpret the data for Turkey from "My Migraine Voice," an online survey of individuals suffering from frequent migraine attacks (≥4 days/month with migraine headaches) who had not benefited from existing prophylactic therapies, conducted in 31 countries to investigate the burden of migraine for the individual and the society. METHODS: Based on a set of predetermined criteria (90% of the patients must have used prophylactic therapy, and 80% of them must have needed to change therapy), patients who had ≥ 4 days in a month with migraine headache in the past 3 months were asked to take an online survey of 88 questions. The study included questions aimed at determining the burden of disease during not only the headache phase, but also the prodrome and postdrome phases, as well as a questionnaire for determining the Reduction of Overall Activity and Productivity at Work ((WPAI: GH). RESULTS: A total of 237 patients from Turkey were included in the study. 62% of the patients stated that they were severely or very severely disabled in their daily activities during the headache phase of migraine, and 31% and 34% of the patients reported that they were disabled during the prodrome and postdrome phases, respectively. 28% of the patients stated they had been receiving prophylactic therapy for more than 2 years, and only 84% of these patients reported complete or partial satisfaction with their current therapies. This value was as low as ~70% in patients in whom 2 or more previous drug treatments or therapies had failed. Actively-working patients reported that they had lost 21% of their time at work due to migraine, and the overall loss of workforce was 67%. CONCLUSION: This study showed that migraine can cause disability in an individual's private and professional lives during every stage of migraine, including the prodrome and postdrome phases. This finding will be important for designing future treatments aimed at enhancing the quality of life and productivity of patients who cannot adequately benefit from existing therapies.

Effectiveness of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization as migraine prevention in the United States.

BACKGROUND: Migraine is a common neurological disease that can have a substantial impact on patients' lives and on society. Erenumab, a fully human monoclonal antibody that targets the calcitonin gene-related peptide receptor, was specifically developed for migraine prevention. The efficacy of erenumab has been established in several clinical trials; however, the real-world comparative effectiveness of erenumab has not been fully investigated. OBJECTIVE: To evaluate the real-world impact of erenumab and onabotulinumtoxinA on acute medication usage and health care resource utilization (HCRU) among patients with migraine in the United States. METHODS: This retrospective US claims analysis (Optum's deidentified Clinformatics Data Mart Database) evaluated patients aged at least 18 years diagnosed with migraine who initiated erenumab or onabotulinumtoxinA between May 1, 2018, and September 30, 2019 (index date: first erenumab/onabotulinumtoxinA claim). Cohorts were matched 1:1 using the propensity score (PS) method (greedy match with caliper = 0.1). Stratification was performed based on gender, chronic migraine without aura diagnosis, onabotulinumtoxinA use, and acute/preventive drug use. The impact of erenumab and onabotulinumtoxinA on acute medication usage and HCRU was assessed in the 6-month post-index period. An exploratory analysis assessed the impact of erenumab and onabotulinumtoxinA on a composite endpoint of: (1) outpatient visit with a migraine diagnosis and associated acute medication claim, (2) hospital admission with a primary migraine diagnosis, or (3) emergency department visit with a primary migraine diagnosis. PS-matched data were used for comparative analyses; logistic regression with covariate adjustment was used for dichotomous variables, and a negative binomial model was used for count variables, with odds ratios or rate ratios (RRs) and 95% CIs calculated. RESULTS: Following stratified PS matching, 1,338 patients were included in both cohorts. At 6 months, the adjusted average number of claims per person for any acute medication was significantly lower in the erenumab cohort (1.13 vs 1.29 in the onabotulinumtoxinA cohort; RR = 0.88; 95% CI = 0.80-0.96; P = 0.0069), although the difference in the number of claims for triptans and barbiturates was statistically nonsignificant. The adjusted average number of all-cause and migraine-specific visits per person to health care providers was generally lower in the erenumab cohort compared with the onabotulinumtoxinA cohort. Patients in the erenumab cohort had a significantly lower number of composite events (0.44 vs 0.69 in the onabotulinumtoxinA cohort; RR = 0.63; 95% CI = 0.56-0.71; P < 0.0001). Similarly, the adjusted proportion of patients with any of the 3 composite events was lower in the erenumab cohort (31.7% vs 44.3% in the onabotulinumtoxinA cohort; OR = 0.59; 95% CI = 0.49-0.70; P < 0.0001). CONCLUSIONS: In this retrospective claims analysis study, erenumab significantly reduced acute medication usage (opioids and nonsteroidal anti-inflammatory drugs; any acute medication when analyzed together) and HCRU to a greater extent than onabotulinumtoxinA. DISCLOSURES: This study was supported by Novartis Pharma AG. Novartis employees contributed to the study design, analysis of the data, and the decision to publish the results. Fang, Abdrabboh, Glassberg, Vo, and Ferraris are employed by Novartis. Zhou and Shen are employed by KMK Consulting, Inc., which received funding from Novartis to conduct the study. Tepper reports grants from Allergan, Amgen, ElectroCore, Eli Lilly, Lundbeck, Neurolief, Novartis, Satsuma, and Zosano, outside the submitted work; personal fees from Dartmouth-Hitchcock Medical Center, American Headache Society, Thomas Jefferson University, Aeon, Align Strategies, Allergan/AbbVie, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, Becker Pharmaceutical Consulting, BioDelivery Sciences International, Biohaven, ClearView Healthcare Partners, CoolTech, CRG, Currax, Decision Resources, DeepBench, DRG, Eli Lilly, Equinox, ExpertConnect, GLG, Guidepoint Global Healthcare Consultancy Group, Health Science Communications, HMP Communications, Impel, InteractiveForums, M3 Global Research, Magellan Rx Management, Medicxi, Navigant Consulting, Neurorelief, Nordic BioTech, Novartis, Pulmatrix, Reckner Healthcare, Relevale, SAI MedPartners, Satsuma, Slingshot Insights, Spherix Global Insights, Sudler and Hennessey, Synapse Medical Communications, System Analytic, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano, Krog and Partners, and Lundbeck, outside the submitted work; and CME honoraria from American Academy of Neurology, American Headache Society, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Headache Cooperative of New England, Henry Ford Hospital, Detroit, Inova, Medical Learning Institute PeerView, Medical Education Speakers Network, Miller Medical Communications, North American Center for CME, Physicians' Education Resource, Rockpointe, ScientiaCME, WebMD/Medscape. The abstract and poster of these results were presented at The Migraine Trust Virtual Symposium (MTIS), October 3-9, 2020.

Healthcare resource use and indirect costs associated with migraine in Italy: results from the My Migraine Voice survey.

AIMS: To evaluate the healthcare resource use (HRU) and cost of lost productivity due to migraine among Italians with ≥4 monthly migraine days (MMDs), with a focus on those with ≥2 prior preventive treatment failures (TFs). MATERIALS AND METHODS: Data from Italian participants from the My Migraine Voice survey were used to assess migraine-related HRU and migraine's impact on work productivity and daily activities using the Work Productivity and Activity Impairment questionnaire. The mean, annualized cost of lost productivity was estimated using the Human Capital Approach and extrapolated to employed Italian population with ≥4 MMDs to calculate the overall migraine-related indirect cost burden in Italy. RESULTS: Data of 420 participants, enrolled between September 2017 and February 2018, were analyzed (mean age: 38.5 years, 81.2% women, 37.8% with ≥2 TF). During a 6-month period, 57.6% of participants visited general practitioners (mean visits: 4.5), 31.9% neurologists (mean visits: 2.6), and 26.4% headache specialists (mean visits: 2.8). Overall, 32.0% of participants had ≥1 emergency room visit (mean visits: 2.8) and 15.0% had ≥1 hospitalization (mean visits: 2.9) because of migraine in the past 12 months. Participants who were employed (N = 215) reported 15.5% absenteeism, 45.3% presenteeism, 53.8% overall work impairment, and 52.6% activity impairment. The mean annualized indirect cost was estimated to be €14,368. The annual indirect cost burden was estimated to be €7.6 billion for the employed Italian population with ≥4 MMDs. The impact of migraine was particularly high among the ≥2 TF subgroups on all parameters. The indirect cost was estimated to be €15,881 (€5,007 attributed to absenteeism). CONCLUSION: Migraine-related HRU and indirect costs are high among individuals with ≥4 MMDs (particularly those with ≥2 TF). There is a need for more effective treatments and better management of migraines to reduce the functional and economic burden among this difficult-to-treat population.

Impact of erenumab on acute medication usage and health care resource utilization among migraine patients: a US claims database study.

BACKGROUND: Migraine is one of the leading causes of disability worldwide. Erenumab is a fully human monoclonal antibody that targets the calcitonin gene-related peptide (CGRP) receptor. This study aimed to evaluate real-world evidence on the impact of erenumab on acute medication usage and health care resource utilization (HCRU) among migraine patients. METHODS: This retrospective effectiveness study utilized the US Optum's de-identified Clinformatics® Data Mart database to identify migraine patients initiating erenumab between May 1, 2018 and September 30, 2019. Patients had to be at least 18 years old, with a minimum of three doses for erenumab in the 6-month post-index period and continuous medical/pharmacy coverage in the 12-month pre- and 6-month post-index period. The date of the first claim for erenumab served as the index date. Use of acute medications overall and at different drug class level, and HCRU were compared during the 6-month pre- vs. post-index period. Impact of erenumab on a composite endpoint of three possible events: 1) outpatient visit with a diagnosis of migraine and an associated acute medication claim within 7 days of the visit, 2) hospital admission with a primary diagnosis for migraine, or 3) emergency room visit with a primary diagnosis for migraine (any events that occurred ≤3 days apart were counted only once) was also evaluated. RESULTS: The analysis included 3171 identified patients. At 6 months, following initiation of erenumab, acute medication use including the number of types of acute medication, number of claims of each medication and % of patients who received acute medication, and HCRU were significantly decreased. For the composite outcome, the mean number of events decreased from 1.03 to 0.77 (rate ratio: 0.75; 95% CI: 0.71 to 0.79; P < 0.0001). A decrease in the proportion of patients with any of the three events was also observed (52.7% vs. 39.5%, P < 0.0001). CONCLUSION: In this retrospective analysis, erenumab was associated with significantly reduced acute medication use and HCRU in a real-world setting, hence significantly reducing the burden of the disease. A composite endpoint could be used as a proxy to evaluate the burden of migraine attacks; however, further research is needed.

Cost-Effectiveness of Erenumab for the Preventive Treatment of Migraine in Patients with Prior Treatment Failures in Sweden.

BACKGROUND: Migraine is a common neurological disease that disproportionately affects females and has a peak incidence during productive years, resulting in significant burden. OBJECTIVE: The aim of the study was to determine the cost effectiveness of erenumab for the preventive treatment of migraine. METHODS: A hybrid decision-tree plus Markov model was developed to evaluate the cost effectiveness of erenumab as a migraine treatment compared with best supportive care only for patients experiencing at least 4 monthly migraine days for whom at least two prior preventive treatments had failed. Clinical efficacy data were based on results from four randomized controlled trials of erenumab against placebo. The primary outcomes were costs, migraine days, and quality-adjusted life-years (QALYs). An incremental cost-effectiveness ratio (ICER) was estimated as the cost per QALY gained. The cost per migraine day avoided was also estimated, as were disaggregated direct and indirect costs. The analysis was conducted from Swedish societal and healthcare system perspectives based on total migraine, chronic migraine and episodic migraine populations, using a discount rate of 3% applied to both costs and health benefits and using year 2019 values. RESULTS: In the base-case deterministic analyses, erenumab treatment resulted in ICERs of Swedish krona (SEK) 34,696 (€3310) and SEK301,565 (€28,769) per QALY gained in the total migraine and episodic migraine populations, respectively. Erenumab was dominant in the chronic migraine population. In the total migraine population, the use of erenumab resulted in a net benefit to society of SEK81,739 (€7773) per patient, assuming a willingness-to-pay threshold of SEK300,000 (€28,528) per QALY. CONCLUSIONS: Our analysis suggests that erenumab is a cost-effective treatment for migraine with a willingness-to-pay threshold of SEK300,000 per QALY.

The Humanistic and Economic Burden of Migraine in Europe: A Cross-Sectional Survey in Five Countries.

INTRODUCTION: Prior studies have estimated the burden of migraine in patients suffering from ≥ 4 monthly headache days (MHDs), but the burden experienced by migraineurs suffering from one to three (1-3) MHDs is unknown. The aim of this study was to examine the incremental burden of migraine in terms of health-related quality of life (HRQoL), impairments to work and daily activities, and healthcare resource utilization (HRU) in five European countries (France, Germany, Italy, Spain, and the UK (EU5]), by comparing migraineurs with ≥ 4 MHDs and migraineurs with 1-3 MHDs. METHODS: The sample for this retrospective cross-sectional study was collected from the 2017 National Health and Wellness Survey (N = 62,000). The Short-Form 12-Item Health Survey Instrument, version-2 physical and mental component summary (PCS and MCS) scores, Short-Form 6-dimensions (SF-6D), EuroQoL 5-dimensions (EQ-5D) and EuroQoL visual analog scale (VAS) scores, impairments to work productivity and daily activities (Work Productivity and Activity Impairment [WPAI] Questionnaire) scores, and HRU were compared between migraineur groups with ≥ 4 MHDs (4-7, intermediate-frequency episodic migraine; 8-14, high-frequency episodic migraine; ≥ 15 chronic migraine) and the migraineur subgroup with 1-3 MHDs (low-frequency episodic migraine) using generalized linear modeling after adjusting for covariates. RESULTS: Data from a total of 62,000 survey respondents were examined, of whom 1323 and 1569 were considered to have 1-3 MHDs and ≥ 4 MHDs (4-7 MHDs [n = 783]; 8-14 MHDs [n = 429]; ≥ 15 MHDs [n = 357]), respectively. The adjusted HRQoL was significantly lower in the 4-7 MHDs (for MCS and SF-6D scores; p < 0.0001) and 8-14 MHDs subgroups (for MCS, SF-6D, EQ-5D, and EuroQoL VAS scores, p < 0.0001; for PCS scores, p = 0.0007) than in the 1-3 MHDs subgroup. Migraineurs with 4-7 and 8-14 MHDs reported higher activity impairment and more frequent visits to healthcare providers (all p < 0.0001) and neurologists (p = 0.0006 and p < 0.0001, respectively) compared to the 1-3 MHDs subgroup. Migraineurs with ≥ 15 MHDs had significantly lower HRQoL and increased WPAI scores and HRU than the 1-3 MHDs subgroup. CONCLUSIONS: This study provides evidence supporting the incremental burden of migraine, characterized by poorer HRQoL and increased WPAI scores and greater HRU, among migraineurs experiencing ≥ 4 MHDs compared with migraineurs experiencing 1-3 MHDs in the EU5.

United States Patients' Perspective of Living With Migraine: Country-Specific Results From the Global "My Migraine Voice" Survey.

BACKGROUND: Migraine is associated with debilitating symptoms that can affect daily functioning. "My Migraine Voice" was a large, cross-sectional, multi-country online survey aimed at understanding disease burden directly from people with migraine. OBJECTIVE: This study reports on the social and economic impacts of migraine, specifically the impact on activities of daily living and the costs of migraine, from the point of view of people with migraine in the United States. METHODS: The online survey was administered to adults with a self-reported diagnosis of migraine who experienced 4 or more monthly migraine days each month for the previous 3 months. Prespecified screening quotas were used so that 90% of respondents reported current or past use of preventive migraine medication, 80% of whom switched treatment (ie, changed their prescribed preventive medication at least once). The remaining 10% were preventive treatment naïve (ie, never used any prescribed preventive medication). Burden of migraine on activities of daily living and caregivers (eg, functional limitations, fear of next migraine attack, sleep problems) and economic burden (eg, out-of-pocket costs, impact on work productivity using the validated work productivity and activity impairment questionnaire) reported by respondents from the United States are presented. Results are stratified by employment status, migraine frequency (chronic vs episodic migraine), and history of preventive treatment. RESULTS: Thousand hundred and one individuals with migraine from the United States responded to the survey. Respondents reported limitations completing daily activities during all migraine phases, including during the premonitory/aura and postdrome phases. Most (761/1101 (69%)) relied on family, friends, or others for help with daily tasks and reported being helped a median of 9 days (25th percentile 5 days, 75th percentile 15 days) within the last 3 months. Respondents with chronic migraine reported being helped for more days (median 10 days, 25th percentile 5 days, 75th percentile 23 days) in the last 3 months. Almost all (962/1101 (87%)) experienced sleep difficulties and 41% (448/1101) (48% (336/697) of those with 2 or more preventive treatment failures) were very or extremely fearful of a next migraine attack. Median (25th percentile, 75th percentile) monthly out-of-pocket costs of $90.00 ($30.00, $144.00) in doctor's fees (n = 504), $124.00 ($60.00, $234.00) in health insurance (n = 450), $40.00 ($20.00, $100.00) for prescriptions (n = 630), and $50.00 ($0.00, $100.00) for complementary therapies (n = 255) were reported. Those with 2 or more preventive treatment failures reported higher monthly out-of-pocket doctor fees (median $99.00 ($30.00, $150.00), n = 388). Among employed respondents (n = 661), migraine resulted in 22% absenteeism, 60% presenteeism, 65% work productivity loss, and 64% activity impairment. CONCLUSIONS: Migraine impacts individuals' activities of daily living, work-life, and financial status, especially individuals with high needs, namely those with 4 or more monthly migraine days and prior treatment failures. People with migraine are impaired during all migraine phases, experience fear of their next migraine attack and sleep difficulties, and pay substantial monthly out-of-pocket costs for migraine. Burden is even greater among those who have had 2 or more preventive treatment failures. Impacts of migraine extend beyond probands to caregivers who help people with migraine with daily tasks, employers who are affected by employee absenteeism, presenteeism, and reduced productivity, and society which is burdened by lost and reduced economic productivity and healthcare costs.

Economic evaluations in migraine: systematic literature review and a novel approach.

Background: For novel migraine therapies, economic evaluations will be required to understand the trade-offs between additional health benefit and additional cost. The purpose of this study was to conduct a systematic literature review (SLR) to identify previous economic evaluations in migraine from the United Kingdom or Irish perspective to critically appraise these evaluations and to propose, if necessary, a novel modelling approach that can be used for future economic evaluations of migraine therapies.Methods: An SLR was conducted to identify previous economic evaluations of preventive migraine treatments. Key opinion leaders were consulted to determine the criteria for a robust migraine economic evaluation. Economic evaluations identified in the SLR were appraised against these criteria, and a novel cost-effectiveness model structure was then proposed.Results: Eight records reporting on published economic evaluations were identified and critically appraised for general quality. Expert consultation provided 6 recommendations on the ideal model structure for migraine that is both clinically and economically meaningful. A decision-tree plus Markov structure was then developed as a cost-effectiveness model for migraine therapies where each health state is associated with a patient distribution across monthly migraine day (MMD) frequencies.Conclusions: Future migraine economic evaluations should allow for assessments across the full spectrum of migraine, a response-based stopping rule, and the estimation of benefits and resource costs based on MMD frequency. The approach proposed in this paper captures all of the desired elements for an economic evaluation of migraine therapy and is suitable to assess new migraine therapies.

Associations Between Headache-Free Days and Patient-Reported Outcomes Among Migraine Patients: A Cross-Sectional Analysis of Survey Data in Europe.

INTRODUCTION: Migraine imposes a substantial burden on patients, society, and healthcare systems. This study aimed to assess the associations between the number of headache-free days (HFDs) and health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), and healthcare resource utilization (HRU) in patients with migraine in the EU5 (France, Germany, Italy, Spain, and the United Kingdom). METHODS: This retrospective cross-sectional study collected survey responses from adults aged ≥ 18 years from the 2017 National Health and Wellness Survey (N = 62,000). Migraine patients with a physician's diagnosis of migraine and who had experienced at least 4 monthly headache days in the prior month were included (N = 1569). Number of HFDs was compared with Short-Form 12-Item Survey Instrument, version 2 (SF-12v2) physical and mental component summary scores (PCS and MCS), Short-Form-6D (SF-6D) and EuroQoL-5D (EQ-5D) scores, WPAI, and HRU in migraine patients. Correlation analyses were conducted to test the bivariate associations, whereas generalized linear models were used for multivariable analyses. RESULTS: An increase of 1 HFD was associated with average increases of 0.171, 0.306, 0.003, and 0.008 points for MCS, PCS, SF-6D utility score, and EQ-5D index score, respectively (p < 0.001 for all). Extrapolating the results to a tenfold increase in monthly HFDs corresponded to clinically meaningful increases in PCS and EQ-5D scores. An increase of 1 HFD was associated with expected average decreases in absenteeism of 3.9% and presenteeism of 2.1%. Further, an increase of 1 HFD was associated with expected decreases in HCP visits and neurologist visits of 1.0% and 4.7%, respectively. CONCLUSION: An increase in the number of HFDs was associated with better health-related outcomes in patients suffering from migraine. Further, the results demonstrate a need for more effective treatments that can reduce migraine frequency and thus improve HRQoL, increase work productivity, and reduce both activity impairment and HRU. FUNDING: Novartis Pharma AG, Switzerland.

Real-world healthcare resource utilization related to migraine treatment failure: a panel-based chart review in France, Germany, Italy, and Spain.

Aims: This retrospective chart review examined the six-month migraine-related healthcare resource use (HRU) among European patients who had ≥4 migraine days per month and previously failed at least two prophylactic migraine treatments. Methods: Neurologists, headache specialists, and pain specialists in France, Germany, Italy, and Spain who treated ≥10 patients with migraine in 2017 were recruited (April-June 2018) to extract anonymized patient-level data. Eligible physicians randomly selected charts of up to five adult patients with clinically-confirmed migraine, ≥4 migraine days in the month prior to the index date, and had previously failed at least two prophylactic migraine treatments. Treatment failure was defined as discontinuation due to lack of efficacy and/or tolerability. Demographic and disease characteristics as of the index date, and migraine-related HRU incurred during the 6-month study period, were recorded. Results: A total of 104 physicians contributed 168 charts for patients (63% female). On average, patients were 38 years old and failed 2.3 prophylactic treatments as of the index date. During the study period, 83% of patients had ≥1 outpatient visit for migraine in the physician's office, and 27% went to the ER/A&E. Approximately 5% of patients were hospitalized for migraine, with an average of one hospitalization and an average length of stay of 3 days. Approximately 39% of patients had ≥1 blood test, 22% had ≥1 magnetic resonance imaging, 17% had ≥1 electroencephalogram, and 13% had ≥1 computerized tomography scan. Visits to other healthcare providers were common. Limitations: This study is subject to the limitations of chart review studies, such as errors in data entry. Conclusions: Across four European countries, the HRU burden of migraine among patients who previously failed at least two prophylactic treatments was high, indicating a need for more effective prophylactic treatments to appropriately manage migraine and reduce the HRU burden attributable to this common disorder.

Migraine-related healthcare resource use in the emergency department setting: a panel-based chart review in France, Germany, Italy, and Spain.

Objective: Migraine is a common, disabling condition typically characterized by severe headache, nausea, and/or light and sound sensitivity. This study assessed migraine-related health resource utilization (HRU) occurring in the emergency room/accident & emergency department (ER/A&E) setting among European patients with 4 or more migraine days per month. Methods: Patient-level clinical and HRU data were collected via chart extraction by ER/A&E physicians in France, Germany, Italy, and Spain. Eligible patients had 4 or more migraine days in the month prior to a migraine-related ER/A&E visit and a history of migraine, among other criteria. The index date for each patient was defined as the date of an ER/A&E visit for migraine on or after January 1, 2013. Physician and ER/A&E characteristics, patient and disease characteristics, treatment history, migraine-medication used, and migraine-related HRU (i.e. procedures) during the ER/A&E visit were assessed. Descriptive analyses were conducted in the pooled population, and a sensitivity analysis was performed by country. Results: A total of 467 eligible patient's charts (120 in France, 120 in Germany, 107 in Italy, and 120 in Spain) were provided by 136 physicians (36 in France, 36 in Germany, 28 in Italy, and 36 in Spain). On average, patients spent nearly 8 hours in the ER/A&E. Approximately 82% of patients received a blood test, 62% received an electrocardiography, and 46% received a cranial computerized tomography scan. Despite the majority of patients already using acute or prophylactic treatment upon visiting the ER/A&E, almost all patients were administered or prescribed migraine treatment during the visit. Approximately 21% of patients were admitted to the hospital, and over half of patients were referred to a neurologist or headache specialist. Conclusions: European patients who had four or more migraine days in the month prior to a migraine-related ER/A&E visit had high HRU associated with the visit.

Health state utilities associated with attributes of migraine preventive treatments based on patient and general population preferences.

PURPOSE: While previous studies have estimated health state utilities associated with migraine severity and frequency, migraine treatments vary in other ways that may have an impact on patients' quality of life, preference, and utility. The purpose of this study was to estimate utilities associated with migraine treatment attributes including route of administration and treatment-related adverse events (AEs). METHODS: In time trade-off interviews, migraine patients and general population participants in the UK valued health state vignettes drafted based on literature, medication labels, and clinician interviews. All respondents valued migraine health states varying in route of administration. Each participant also valued eight health states (randomly selected from a total of 15) that added the description of an AE to a migraine health state. RESULTS: A total of 400 participants completed interviews (200 general population [49.0% female; mean age = 43.6 years]; 200 migraine patients [74.5% female; mean age = 45.8 years]). In the general population sample, mean utilities of health states without aura were 0.79 with daily oral medication, 0.78 with one injection per month, and 0.72 with 31-39 injections once every 3 months. The greatest disutilities (i.e., decreases in utility) were for AEs associated with oral medications (e.g., - 0.060 [fatigue] and - 0.098 [brain fog]). Differences among health states followed the same pattern in the patient sample as in the general population sample. CONCLUSIONS: Utilities estimated from the general population sample may be used to represent route of administration and AEs in cost-utility models. Results from the patient sample indicate that these treatment characteristics have an impact on patient preference.

Benefit-risk assessment of erenumab and current migraine prophylactic treatments using the likelihood of being helped or harmed.

OBJECTIVE: This study evaluated the benefit-risk profile of erenumab relative to other therapies approved for migraine prophylaxis and available in the majority of European countries. METHODS: Trials were identified via a published systematic literature review updated to December 2017 using MEDLINE. Erenumab's pivotal trials study reports were also included (NCT02066415, NCT02456740). From these sources, ≥ 50% responder rates and discontinuations due to adverse events were extracted to generate numbers needed to treat and harm and likelihood of being helped or harmed, a quantitative benefit-risk measure. RESULTS: Eleven articles (nine randomized clinical trials) met the inclusion/exclusion criteria. Low numbers needed to treat (range: 4-13) were observed for most treatments, while numbers needed to harm showed substantial differences (erenumab's higher numbers needed to harm indicating better tolerability). In chronic and episodic migraine, likelihoods of being helped or harmed for erenumab 70 mg were 143 and 167, and 42 and 167 for erenumab 140 mg. Likelihoods of being helped or harmed in chronic migraine were 2 and 3 for topiramate (two studies) and 4 for onabotulinumtoxinA. In episodic migraine, likelihoods of being helped or harmed were 2 for topiramate and 2 for propranolol. CONCLUSIONS: While all prophylactic treatments were more likely to help than harm (likelihood of being helped or harmed > 1), erenumab showed a likelihood of being helped or harmed of high magnitude, supporting its favorable benefit-risk profile across the entire migraine frequency spectrum, in contrast with other prophylactic treatments.