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.

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.

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.

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.

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.

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.

My Migraine Voice survey: a global study of disease burden among individuals with migraine for whom preventive treatments have failed.

BACKGROUND: Migraine is associated with many debilitating symptoms that affect daily functioning. My Migraine Voice is a large global cross-sectional study aimed at understanding the full burden and impact of migraine directly from patients suffering from ≥4 monthly migraine days (MMDs) with a history of prophylactic treatment failure. METHODS: This study was conducted worldwide (31 countries across North and South Americas, Europe, the Middle East and Northern Africa, and the Asia-Pacific region) using an online survey administered to adults with migraine who reported ≥4 MMDs in the 3 months preceding survey administration, with pre-specified criteria of 90% having used preventive migraine treatment (80% with history of ≥1 treatment failure). Prophylactic treatment failure was defined as a reported change in preventive medication by individuals with migraine for any reason, at least once. RESULTS: In total, 11,266 individuals participated in the survey. Seventy-four percent of the participants reported spending time in darkness/isolation due to migraine (average: 19 h/month). While 85% of all respondents reported negative aspects of living with migraine (feeling helpless, depressed, not understood), sleeping difficulties (83%), and fear of the next attack (55%), 57% shared ≥1 positive aspect (learning to cope, becoming a stronger person). Forty-nine percent reported feeling limited in daily activities throughout all migraine phases. Migraine impact on professional, private, or social domains was reported by 87% of respondents (51% in all domains). In the previous 12 months, 38% of respondents had visited the emergency department (average: 3.3 visits), whereas 23% stayed in hospital overnight (average: 3.2 nights) due to migraine. CONCLUSIONS: The burden of migraine is substantial among this cohort of individuals with at least 4 migraine days per month and for whom at least 1 preventive migraine treatment had failed. Interestingly, respondents reported some positive aspects in their migraine journey; the greater resilience and strength brought on by coping with migraine suggests that if future treatments could address existing unmet needs, these individuals with migraine will be able to maximize their contribution to society.

Analysis of number needed to treat for droxidopa in patients with symptomatic neurogenic orthostatic hypotension.

BACKGROUND: Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine ß-hydroxylase deficiency, or nondiabetic autonomic neuropathy. The efficacy and safety of droxidopa were assessed by determining the number needed to treat (NNT) and the number needed to harm (NNH). METHODS: Data collected in randomized, placebo-controlled clinical studies in adults with a clinical diagnosis of symptomatic nOH were pooled for efficacy and safety analyses. NNT and NNH were calculated as reciprocals of the risk difference (difference in event rates) for droxidopa versus placebo. RESULTS: The NNT for droxidopa for improvement in OHSA Item 1 was <10. The NNH for adverse events (AEs) leading to discontinuation in the pooled studies was 81. The likelihood of being helped or harmed (LHH) calculated from pooled analysis of the NNT for ≥2 units of improvement in OHSA Item 1 score and the NNH for discontinuations due to AEs were 7.8, 8.8, 3.1, and 3.5 for weeks 1, 2, 4, and 8 after randomization, respectively. CONCLUSIONS: Droxidopa is efficacious for treatment of nOH, with an NNT below 10 and an acceptable tolerability profile with NNH ranging from 23 to 302 in the pooled analysis of frequently occurring AEs. Based on the LHH for the pooled analysis at week 1, droxidopa is 7.8 times more likely than placebo to show a clinical benefit than result in discontinuation because of an AE. TRIAL REGISTRATIONS: ClinicalTrials.gov identifiers: NCT00782340 , first received October 29, 2008; NCT00633880 , first received March 5, 2008; and NCT01176240 , first received July 30, 2010.

A population-based study of childhood respiratory morbidity after severe lower respiratory tract infections in early childhood.

OBJECTIVES: To estimate the risk of childhood chronic respiratory morbidity among those hospitalized for severe lower respiratory tract infection (LRTI) in early childhood, and to determine whether severe LRTI is an independent predictor. STUDY DESIGN: The population-based Régie de l'Assurance Maladie du Québec datasets were used to identify LRTI hospitalizations before age 2 years in a birth cohort from 1996-1997 and a comparison cohort of children without an LRTI hospitalization. The incidence rate and incidence rate ratio of chronic respiratory morbidity before age 10 years were calculated, and multivariable logistic regression was performed to estimate the impact of LRTI hospitalization on chronic respiratory morbidity. Population-attributable risks of chronic respiratory morbidity due to severe LRTI were estimated, and similar analyses were performed for respiratory syncytial virus LRTI. RESULTS: Among the birth cohort, 7104 patients (4.9%) were hospitalized for LRTI before age 2 years. By age 10 years, 52.5% of the LRTI cohort and 27.9% of the nonhospitalized cohort had developed chronic respiratory morbidity; the incidence rate ratio was 1.81 (95% CI, 1.76-1.86) for males and 1.91 (95% CI, 1.84-1.99) for females. The OR for chronic respiratory morbidity based on LRTI hospitalization before age 2 years was 2.79 (95% CI, 2.66-2.93). The population-attributable risk of chronic respiratory morbidity due to any LRTI was approximately 25%, and that for respiratory syncytial virus LRTI was similar. CONCLUSIONS: Hospitalization of young children for LRTIs is associated with two-fold increased risk of childhood chronic respiratory morbidity, demonstrating the ongoing impact of LRTI in infancy.

The economic burden of prematurity in Canada.

BACKGROUND: Preterm birth is a major risk factor for morbidity and mortality among infants worldwide, and imposes considerable burden on health, education and social services, as well as on families and caregivers. Morbidity and mortality resulting from preterm birth is highest among early (< 28 weeks gestational age) and moderate (28-32 weeks) preterm infants, relative to late preterm infants (33-36 weeks). However, substantial societal burden is associated with late prematurity due to the larger number of late preterm infants relative to early and moderate preterm infants. METHODS: The aim in this study was to characterize the burden of premature birth in Canada for early, moderate, and late premature infants, including resource utilization, direct medical costs, parental out-of-pocket costs, education costs, and mortality, using a validated and published decision model from the UK, and adapting it to a Canadian setting based on analysis of administrative, population-based data from Québec. RESULTS: Two-year survival was estimated at 56.0% for early preterm infants, 92.8% for moderate preterm infants, and 98.4% for late preterm infants. Per infant resource utilization consistently decreased with age. For moderately preterm infants, hospital days ranged from 1.6 at age two to 0.09 at age ten. Cost per infant over the first ten years of life was estimated to be $67,467 for early preterm infants, $52,796 for moderate preterm infants, and $10,010 for late preterm infants. Based on population sizes this corresponds to total national costs of $123.3 million for early preterm infants, $255.6 million for moderate preterm infants, $208.2 million for late preterm infants, and $587.1 million for all infants. CONCLUSION: Premature birth results in significant infant morbidity, mortality, healthcare utilization and costs in Canada. A comprehensive decision-model based on analysis of a Canadian population-based administrative data source suggested that the greatest national-level burden is associated with moderate preterm infants due to both a large cost per infant and population size while the highest individual-level burden is in early preterm infants and the largest total population size is in late preterm infants. Although the highest medical costs are incurred during the neonatal period, greater resource utilization and costs extend into childhood.

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.

The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is the leading cause of childhood morbidity. Although also an important cause of childhood mortality worldwide, the impact of key risk factors has not been established. A systematic review of 34 articles reporting case fatality rates in young children hospitalized for severe RSV LRTI, according to the presence of underlying RSV risk factors, was conducted. The weighted mean case fatality rate was 1.2% (range, 0-8.3%; median, 0%; n = 10) among preterm infants; 5.2% (range, 2.0-37.0%; median, 5.9%; n = 7) among children with CHD; and 4.1% (range, 0-10.5%; median, 7.0%; n = 6) among children with BPD. Case fatality estimates among children not at high risk (n = 6) ranged from 0% to 1.5% (weighted mean, 0.2%; median, 0.0%). Fatality during hospitalization for severe RSV LRTI is rare among children not at high risk, but occurs more commonly among children at higher risk of RSV LRTI.

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.

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.

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.

Acute care utilization due to hospitalizations for pediatric lower respiratory tract infections in British Columbia, Canada.

BACKGROUND: Pediatric LRTI hospitalizations are a significant burden on patients, families, and healthcare systems. This study determined the burden of pediatric LRTIs on hospital settings in British Columbia and the benefits of prevention strategies as they relate to healthcare resource demand. METHODS: LRTI inpatient episodes for patients <19 years of age during 2008-2010 were extracted from the BC Discharge Abstract Database. The annual number of acute care beds required to treat pediatric LRTIs was estimated. Sub-analyses determined the burden due to infants <1 year of age and high-risk infants. Population projections were used to forecast LRTI hospitalizations and the effectiveness of public health initiatives to reduce the incidence of LRTIs to 2020 and 2030. RESULTS: During 2008-2010, LRTI as the primary diagnosis accounted for 32.0 and 75.9% hospitalizations for diseases of the respiratory system in children <19 years of age and infants <1 year of age, respectively. Infants <1 year of age accounted for 47 and 77% hospitalizations due to pediatric LRTIs and pediatric LRTI hospitalizations specifically due to respiratory syncytial virus (RSV), respectively. The average length of stay was 3.1 days for otherwise healthy infants <1 year of age and 9.1 days for high-risk infants (P <0.0001). 73.1% pediatric LRTI hospitalizations occurred between November and April. Over the study timeframe, 19.6 acute care beds were required on average to care for pediatric LRTIs which increased to 64.0 beds at the peak of LRTI hospitalizations. Increases in LRTI bed-days of 5.5 and 16.2% among <19 year olds by 2020 and 2030, respectively, were predicted. Implementation of appropriate prevention strategies could cause 307 and 338 less LRTI hospitalizations in <19 year olds in 2020 and 2030, respectively. CONCLUSION: Pediatric LRTI hospitalizations require significant use of acute care infrastructure particularly between November and April. Population projections show the burden may increase in the next 20 years, but implementation of effective public health prevention strategies may contribute to reducing the acute care demand and to supporting efforts for overall pediatric healthcare sustainability.

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.

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.

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.