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.

Uncontrolled asthma across GINA treatment steps 2 - 5 in a large US patient cohort.

OBJECTIVE: Despite advances in treatment, asthma remains uncontrolled in many patients, with increased risk of exacerbation and associated healthcare resource utilization (HCRU). We describe patient characteristics, exacerbations, asthma control, and HCRU using GINA treatment step (GS) as a proxy for asthma severity. . METHODS: Using a large, US, health-claims database, 4 longitudinal cohorts of 517,738 patients in GS2-5, including a subgroup of patients with baseline eosinophil (EOS) counts, were analyzed retrospectively (study period 2010 - 2016). Index for each cohort was patients' first time entering the GS, determined by first claim of first regimen. Uncontrolled asthma was defined according to published criteria as a multi-dimensional measure that includes number of exacerbations. Key variables including, baseline characteristics, post-index exacerbations, and HCRU (all-cause and asthma-specific events) are summarized by descriptive statistics. RESULTS: Uncontrolled asthma was reported in 19.8% patients in GS2, 44.8% in GS3, 49.3% in GS4, and 58.6% in GS5. Annualized mean (SD) rates of exacerbation 12 months post-index generally increased across GS2-5 (0.26 [0.86], 0.32 [0.79], 0.36 [0.83], 0.29 [0.86], respectively). HCRU also increased with increasing GS, with higher HCRU among the uncontrolled cohort within each GS. In patients with EOS ≥300 cells/µL, uncontrolled asthma also increased with increasing GS (21.8%, 43.9%, 50.5%, 67.2% for GS2-5, respectively). CONCLUSIONS: This large database study provides real-world evidence of the substantial degree of uncontrolled asthma in US clinical practice across GS, supporting calls for better asthma management. Healthcare burden tends to increase with lack of control in all groups, highlighting the need for improved patient education, adherence, access, and treatment optimization.Supplemental data for this article can be accessed at publisher's website.

Physician-reported Clinical Unmet Needs, Burden and Treatment Patterns of Paediatric Psoriasis Patients: A US and EU Real-world Evidence Study.

This study is a retrospective analysis using data collected from the Adelphi Paediatric Psoriasis Disease-Specific Programme cross-sectional survey. Despite being treated for their psoriasis, a substantial proportion of paediatric patients presented with moderate (18.3%) or severe (1.3%) disease at sampling; 42.9% and 92.0% had a body surface area (BSA) of >10%, and 38.8% and 100.0% had a Psoriasis Area Severity Index (PASI) score >10, respectively. Overall, 69.9% of patients had only ever been treated with a topical therapy for their psoriasis. For patients with moderate or severe disease at sampling, 16.3% and 14.4% were currently receiving conventional systemics or biologic therapy, respectively. There is a clinical unmet need in this paediatric population; a considerable percentage of patients still experienced moderate or severe disease and persistent psoriasis symptoms, with numerous body areas affected. A significant proportion of patients were undertreated, which may explain the high burden of disease observed.

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.

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.

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.

Real-World Trends in Characteristics of Patients with Migraine Newly Initiated on Erenumab in the USA: A Retrospective Analysis.

INTRODUCTION: This retrospective analysis aimed to characterize patients with migraine initiating erenumab and the shifting or trend of patient characteristics over time in a real-world setting. METHODS: Adult patients with at least one erenumab written prescription/administration between May 1, 2018 and September 30, 2019 were identified from the Optum De-identified Electronic Health Record (EHR) database (index date = date of the first erenumab prescription/administration). Patient demographics and characteristics, acute and preventive medications used prior to initiation of erenumab, and the initial prescriber specialty were examined. In addition, the shifting or trends of patient characteristics over time were analyzed among subgroups of patients based on when they initiated erenumab. RESULTS: A total of 14,774 eligible patients who met inclusion and exclusion criteria were included in the analysis. Most patients were female (86.4%), average age 46.3 (standard deviation [SD] = 13.1) years, Caucasian (88.7%), non-Hispanic (91.8%), and commercially insured (59.8%) at the index date. During the 12-month pre-index period, commonly observed selected comorbid conditions included anxiety (30.6%), depression (28.2%), and cardiovascular diseases (26.4%), and the mean (SD) Elixhauser comorbidity score was 1.7 (5.5). The most common provider specialty at erenumab initiation was neurologist/headache specialist (46.5%). Over time, there was a decrease in mean baseline Elixhauser comorbidity score at erenumab initiation, an increase in general practitioners prescribing initial erenumab, and increased utilization in patients with less severe migraine overall (a proxy of the declining trend in chronic migraine and triptan use). CONCLUSION: Early use of erenumab post approval focused on patients with more severe disease and a high comorbidity index rating. Over time, utilization of this preventive medication occurred in a broader population of patients with migraine, with increased use by general practitioners and those outside of headache centers.

Employee and Employer Benefits From a Migraine Management Program: Disease Outcomes and Cost Analysis.

OBJECTIVE: To assess the impact of a migraine management program offered as a complimentary service by a company within its corporate well-being program. BACKGROUND: Migraine imposes a substantial burden on patients, families, employers, and societies. As migraine primarily affects working-age adults, this has important implications for both employees and employers. Workplace educational and well-being programs positively contribute to employees' productivity, reduce costs related to absenteeism, and improve the quality of life of the employees living with migraine. METHODS: This was a non-interventional cohort study, which followed employees and their family members over time. Participants received 1 telemedicine consultation to determine migraine diagnosis or a high probability of having migraine and 6 sessions of individualized telecoaching from a specialized nurse via a specially developed smartphone application to optimize their migraine management leveraging all appropriate medical and lifestyle options. Participants were evaluated during the program and at 3 months after completion through a series of validated questionnaires including Migraine Disability Assessment (MIDAS), Patient Activation Measure (PAM), and satisfaction with the services offered. A cost analysis was also performed to determine the economic benefit of the program considering the number of completers, dropouts, their associated program costs, MIDAS data, average salary of a Swiss employee in the pharma sector, and working days per year. RESULTS: Of the 141 participants enrolled in the program, 79 completed 6-month and 42 completed 9-month assessments. The total MIDAS scores (mean, standard deviation [SD]) significantly improved from baseline by 54% at Month 6 (15.0 [13.6] vs 6.9 [8.2]; mean [SD] reduction: 8.1 [12.9], 95% confidence interval [CI]: 5.6-10.6; P < .0001) and by 64% at Month 9 (15.4 [14.7] vs 5.6 [6.0]; mean [SD] reduction: 9.8 [14.0], 95% CI: 6.6-13.0; P < .0001). The PAM scores also significantly improved from baseline by 8% at Month 6 (63.8 [10.9] vs 69.6 [12.8]; mean [SD] increase: 5.8 [12.8], 95% CI: 3.2-8.4; P = .003) and 11% at Month 9 (63.5 [10.7] vs 71.3 [12.2]; mean [SD] increase: 7.8 [11.0], 95% CI: 4.3-11.2; P = .003). At Month 6, common coaching lessons and respective action plans focused on progressive muscle relaxation, sleep, hydration, nutrition, general disease education, and stress management. The exit survey showed that the majority of the participants who completed the program had a meaningful and sustained improvement in their overall health and reported a high level of satisfaction with the program. The cost analysis revealed that on average participants gained 10.8 (95% CI: 9.3-12.3) working days/year that were previously lost due to migraine, resulting in a positive return on investment (ROI) of 490% (95% CI: 410%-570%), indicating a higher magnitude of savings that could be achieved by the implementation of such program. In addition to ROI and work productivity gained, participants also gained on average 13.6 (95% CI: 9.9-17.3) migraine-free days/year for their private and social life. CONCLUSION: The employer-sponsored disease management program provided a better understanding of migraine, promoted methods and approaches to improve management by combining medical and lifestyle options leading to significant improvements in migraine symptoms that sustained beyond the intervention, supporting prolonged effectiveness of such programs. The program also provided a high ROI to the employer, supporting that the systematic inclusion of such programs into corporate well-being initiatives can be of significant benefit not only to the impacted individuals but to the employers as well.

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.

Evaluation of exacerbations and blood eosinophils in UK and US COPD populations.

BACKGROUND: Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting ß2-agonist and long-acting muscarinic antagonist). METHODS: In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution. RESULTS: Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included. Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/µL. Patients with ≥2 exacerbations or eosinophil count ≥400 cells/µL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/µL (76.8% vs 76.5%), respectively in the follow-up year. In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/µL; patients with eosinophil count < 150 cells/µL had the lowest variability. Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/µL across the databases. CONCLUSION: A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions. A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/µL.

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.

Burden of Migraine in Europe Using Self-Reported Digital Diary Data from the Migraine Buddy© Application.

INTRODUCTION: Migraine is a neurological disease characterized by recurring attacks that can cause severe disabling pain. This study described the burden of migraine as reported by individuals with migraine in the real world using a mobile application. METHODS: A retrospective, cross-sectional analysis was conducted using data captured through the Migraine Buddy© smartphone application from adult, self-diagnosed individuals with migraine in 17 European countries. Data were analyzed descriptively for the most recent 28-day period reported by users (n = 3900) during the study period (June 2015-July 2016) who were randomly selected on the basis of data completeness (completion rates > 70%) and stratified by migraine headache days/month: 4-7 episodic migraine (EM; n = 1500), 8-14 EM (n = 1500), and chronic migraine (≥ 15; CM; n = 900). RESULTS: More than 95% of users reported that migraine negatively affected their daily activities during at least one migraine attack. Attacks affected 50.5% (184.4 days/year), 26.9% (98 days/year), and 14.5% (53 days/year) of the year among CM, 8-14 EM, and 4-7 EM groups, respectively. On average, 44.8% CM, 40.9% 8-14 EM, and 34.7% of 4-7 EM sufferers, respectively, reported anxiety and/or depression symptoms during migraine attacks. Social or home activities, productivity, and sleep were highly affected, regardless of migraine frequency. Employed respondents (n = 3106) reported an average of 2.3 workdays missed per month and that at least one in four migraines led to work absenteeism; these migraines were commonly reported to have at least moderate to severe levels of pain, corresponding to the inability of persons to perform some or even any activities. Triptans (68%), opioids (46%), and nonsteroidal anti-inflammatory drugs (45%) were self-reported as the most common medicines used. CONCLUSIONS: This study, leveraging patient-reported data collected through a mobile application, demonstrates the high burden and impact of migraine on health-related quality of life, work productivity, and overall well-being of individuals suffering from migraines. FUNDING: Novartis Pharma AG, Switzerland.

Patients' perspective on the burden of migraine in Europe: a cross-sectional analysis of survey data in France, Germany, Italy, Spain, and the United Kingdom.

BACKGROUND: Migraine is a distinct neurological disease that imposes a significant burden on patients, society, and the healthcare system. This study aimed to characterize the incremental burden of migraine in individuals who suffer from ≥4 monthly headache days (MHDs) by examining health-related quality of life (HRQoL), impairments to work productivity and daily activities, and healthcare resource utilization (HRU) in the EU5 (France, Germany, Italy, Spain, United Kingdom). METHODS: This retrospective cross-sectional study used data from the 2016 National Health and Wellness Survey (NHWS; N = 80,600). Short-Form 36-Item Health Survey, version 2 (SF-36v2) physical and mental component summary scores (PCS and MCS), Short-form-6D (SF-6D), and EuroQoL (EQ-5D), impairments to work productivity and daily activities (Work Productivity and Activity Impairment Questionnaire (WPAI), and HRU were compared between migraine respondents suffering from ≥4 MHDs (n = 218) and non-migraine controls (n = 218) by propensity score matching using sociodemographic characteristics. Chi-square, T-tests, and Mann-Whitney tests were performed to determine significant differences between the groups after propensity score matching. RESULTS: HRQoL was lower in migraine individuals suffering from ≥4 MHDs compared with non-migraine controls, with reduced SF-36v2 PCS (46.00 vs 50.51) and MCS (37.69 vs 44.82), SF-6D health state utility score (0.62 vs 0.71), and EQ-5D score (0.68 vs 0.81) (for all, p < 0.001). Respondents with migraine suffering from ≥4 MHDs also reported higher levels of absenteeism from work (14.43% vs 9.46%; p = 0.001), presenteeism (35.52% vs 20.97%), overall work impairment (38.70% vs 23.27%), and activity impairment (44.17% vs 27.75%) than non-migraine controls (for all, p < 0.001). Additionally, HRU was significantly higher for individuals with ≥4 MHDs compared to their matched controls. Consistently, migraine subgroups (4-7 MHDs, 8-14 MHDs and CM) had lower HRQoL, greater overall work and activity impairment, and higher HRU compared to non-migraine controls. CONCLUSIONS: Migraine of ≥4 MHDs was associated with poorer HRQoL, greater work productivity loss, and higher HRU compared with non-migraine controls. The findings of the study suggest that an unmet need exists among individuals suffering from ≥4 MHDs in the EU5 suggesting the need for effective prophylactic treatments to lessen the humanistic and economic burden of migraine.

Effect of interferon beta-1a subcutaneously three times weekly on clinical and radiological measures and no evidence of disease activity status in patients with relapsing-remitting multiple sclerosis at year 1.

BACKGROUND: In the PRISMS study, interferon beta-1a subcutaneously (IFN ß-1a SC) reduced clinical and radiological disease burden at 2 years in patients with relapsing-remitting multiple sclerosis. The study aimed to characterize efficacy of IFN ß-1a SC 44 µg and 22 µg three times weekly (tiw) at Year 1. METHODS: Exploratory endpoints included annualized relapse rate (ARR), 3-month confirmed disability progression (1-point Expanded Disability Status Scale increase if baseline was < 6.0 [0.5-point if baseline was ≥6.0]), active T2 lesions, and no evidence of disease activity (NEDA; defined as no relapses [subanalyzed by relapse severity], 3-month confirmed progression, or active T2 lesions). Effect of IFN ß-1a SC in prespecified patient subgroups was also assessed. RESULTS: Patients were randomized to IFN ß-1a 22 µg (n = 189), 44 µg (n = 184), or placebo (n = 187). At 1 year, IFN ß-1a SC tiw reduced ARR (p < 0.001), risk of disability progression (p ≤ 0.029), and mean number of active T2 lesions per patients per scan (p < 0.001) versus placebo. Clinical and radiological benefits were seen as early as Month 2 and 3. Outcomes in subgroups were consistent with those in the overall population. More patients treated with IFN ß-1a SC tiw achieved NEDA status, versus placebo, regardless of relapse severity (p ≤ 0.006). CONCLUSION: Clinical, radiological, and NEDA outcomes at Year 1 were consistent with Year 2 results. Treatment efficacy was consistent in pre-specified patient subgroups.

Predictive value of early magnetic resonance imaging measures is differentially affected by the dose of interferon beta-1a given subcutaneously three times a week: an exploratory analysis of the PRISMS study.

BACKGROUND: On-treatment magnetic resonance imaging lesions may predict long-term clinical outcomes in patients receiving interferon ß-1a. This study aimed to assess the effect of active T2 and T1 gadolinium-enhancing (Gd+) lesions on relapses and 3-month confirmed Expanded Disability Status Scale (EDSS) progression in the PRISMS clinical trial. METHODS: Exploratory analyses assessed whether active T2 and T1 Gd + lesions at Month 6, or active T2 lesions at Month 12, predicted clinical outcomes over 4 years in PRISMS. RESULTS: Mean active T2 lesion number at Month 6 was significantly lower with interferon beta-1a given subcutaneously (IFN ß-1a SC) 44 µg and 22 µg 3×/week (tiw) than with placebo (p < 0.0001). The presence of ≥4 versus 0 active T2 lesions predicted disability progression at Years 3-4 in the IFN ß-1a SC 22 µg group only (p < 0.05), whereas the presence of ≥2 versus 0-1 active T2 lesions predicted disability progression in the placebo/delayed treatment (DTx) (Years 2-4; p < 0.05) and IFN ß-1a SC 22 µg groups (Years 3-4; p < 0.05). Greater active T2 lesion number at 6 months predicted relapses in the placebo/DTx group only (≥4 vs. 0, Years 1-4; ≥2 vs. 0-1, Years 2-4; p < 0.05), and the presence of T1 Gd + lesions at 6 months predicted disability progression in the IFN ß-1a SC 44 µg group only (Year 1; p < 0.05). The presence of ≥2 versus 0-1 active T2 lesions at 12 months predicted disability progression over 3 and 4 years in the IFN ß-1a SC 44 µg group. CONCLUSION: Active T2 lesions at 6 months predicted clinical outcomes in patients receiving placebo or IFN ß-1a SC 22 µg, but not in those receiving IFN ß-1a SC 44 µg. Active T2 lesions at 12 months may predict outcomes in those receiving IFN ß-1a SC 44 µg and are possibly more suggestive of poor response to therapy than T2 results at 6 months.

Early MRI results and odds of attaining 'no evidence of disease activity' status in MS patients treated with interferon ß-1a in the EVIDENCE study.

INTRODUCTION: 'No evidence of disease activity' (NEDA) is increasingly used as a treatment target with disease-modifying drugs for relapsing multiple sclerosis. METHODS: This post-hoc analysis of the randomised EVIDENCE trial compared interferon beta-1a injected subcutaneously three times weekly (IFN ß-1a SC tiw) with interferon ß-1a injected intramuscularly once weekly (IFN ß-1a IM qw) on NEDA and clinical activity-free (CAF) status. The influence of the frequency of magnetic resonance imaging (MRI) scanning on NEDA and the effect of baseline T1 gadolinium-enhancing (Gd+) lesions on NEDA and CAF were also investigated. RESULTS: More patients in the IFN ß-1a SC tiw group achieved NEDA compared with the IFN ß-1a IM qw group, although rates were lower when monthly MRI scans through 24weeks were included (35.0% vs. 21.6%, respectively; p<0.001) versus the 24-week scan alone (59.5% vs. 41.2%; p<0.001). Absence of baseline Gd+ lesions predicted NEDA through Week 72 in the IFN ß-1a IM qw group (p=0.022), and CAF through Week 48 in patients receiving IFN ß-1a SC tiw (p=0.024). CONCLUSIONS: IFN ß-1a SC tiw was associated with significantly higher rate of NEDA status compared with IFN ß-1a IM qw. Baseline Gd+ lesions augured less frequent CAF or NEDA status. Inclusion of more MRI scans in the analysis reduced rates of NEDA status.

Secondary Use of Data: Non-Interventional Study Best Practices in Planning and Protocol Development.

Well established guidelines already exist that address best practices for Non-Interventional Study (NIS) design and methods. These guidelines provide advice on things to consider while designing a study and developing a protocol, but do not necessarily capture specific details related to the implementation of NIS. The intent of this paper is to propose a best practice for conducting secondary use of data NIS. We propose that the ideal implementation of a NIS should include the development of a strong Study Concept, followed by a detailed Protocol, Analysis Plan, Report, and considerations for Dissemination. We review and discuss common mistakes/pitfalls and key considerations at each step from concept to publication. In many cases in this review, we have also provided suggestions or accessible resources that researchers can apply as a "best practices" guide when planning, conducting, or reviewing this investigative method.

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example.

PURPOSE: Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). METHODS: Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) latrepirdine free base in a fixed sequence. RESULTS: Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. CONCLUSION: Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].