Characterizing mortality in patients with AQP4-Ab+ neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder is an autoimmune disease, causing severe disability due to relapses, but recent mortality data are limited. Among 396 patients seropositive for anti-aquaporin-4 antibody from 2014 to 2020 in the United Kingdom, 39 deaths occurred: 19 (48.7%) were unrelated to disease; 14 (35.9%) were severe disability- or relapse-related; and 4 (10.3%) were attributed to malignancy/infection. Mean annual mortality was 1.92% versus 0.63% in the matched population. The standardized mortality ratio was 3.04 (95% confidence interval 1.67-5.30) with 1.29% excess mortality per year in patients. Median Expanded Disability Status Scale before death was 7.0. Results highlight the importance of preventing relapses that drive disability.

Exploring consumer preferences for cannabis edible products to support public health policy: A discrete choice experiment.

BACKGROUND: In October 2019, cannabis edibles were legalized for sale in Canada for non-medical use. This move was intended to improve public safety by regulating contents (including a maximum 10 mg tetrahydrocannabinol (THC) per package) and packaging to prevent accidental ingestion or over consumption. This study aimed to explore consumer preferences for cannabis edibles to inform cannabis policy. METHODS: We explored the relative importance and trade-offs consumers make for attributes of cannabis edibles using a discrete choice experiment. Attributes included type of edible, price, THC content, cannabis taste, package information, product consistency, product recommendations, and Health Canada regulation. Participants lived in Canada, were 19 years of age or older, and purchased a cannabis edible in the last 12 months. A multinomial logit (MNL) model was used for the base model, and latent class analysis to assess preference sub-groups. This study was approved by the institutional ethics committee. RESULTS: Among 684 participants, the MNL model showed that potency was the most relevant attribute, followed by edible type. A two-group latent class model revealed two very distinct preference patterns. Preferences for group 1 (~65% of sample) were driven primarily by edible type, while for group 2 (~35% of sample) were driven almost entirely by THC potency. CONCLUSION: This study found that consumer preferences for ~65% of consumers of cannabis edibles are being met through regulated channels. The remaining ~35% are driven by THC potency at levels that are not currently available on the licensed market. Attracting this market segment will require reviewing the risks and benefits of restricting THC package content.

Cost-effectiveness of rimegepant oral lyophilisate compared to best supportive care for the acute treatment of migraine in the UK.

AIMS: Migraine is the most common disabling headache disorder and is characterized by recurrent throbbing head pain and symptoms of photophobia, phonophobia, nausea, and vomiting. Rimegepant 75 mg, an oral lyophilisate calcitonin gene-related peptide antagonist, is the first treatment approved for both the acute and preventative treatment of migraine, and the first acute therapy approved in over 20-years. The objective was to assess the cost-utility of rimegepant compared with best supportive care (BSC) in the UK, for the acute treatment of migraine in the adults with inadequate symptom relief after taking at least 2 triptans, or for whom triptans are contraindicated or not tolerated. MATERIALS AND METHODS: A de novo model was developed to estimate incremental costs and quality-adjusted life years (QALYs), structured as a decision tree followed by Markov model. Patients received rimegepant or BSC for a migraine attack and were assessed for response (pain relief at 2-h). Responders and non-responders followed different pain trajectories over 48-h cycles. Non-responders discontinued treatment while responders continued treatment for subsequent attacks, with a proportion discontinuing over time. Data sources included a post-hoc pooled analysis of the phase 3 acute rimegepant trials (NCT03235479, NCT03237845, NCT03461757), and a long-term safety study (NCT03266588). The analysis was conducted from the perspective of the UK National Health Service and Personal Social Services over a 20-year time horizon. RESULTS: Rimegepant resulted in an incremental cost-utility ratio (ICUR) of £10,309 per QALY gained vs BSC, which is cost-effectiveness at a willingness to pay threshold of £30,000/QALY. Rimegepant generated +0.44 incremental QALYs and higher incremental lifetime costs (£4,492). Improved QALYs for rimegepant were a result of less time spent with severe and moderate headache pain. CONCLUSION: This study highlights the economic value of rimegepant which was found to be cost-effective for the acute treatment of migraine in adults unsuitable for triptans.

Examining attributes of retailers that influence where cannabis is purchased: a discrete choice experiment.

BACKGROUND: With the legalization of cannabis in Canada, consumers are presented with numerous purchase options. Licensed retailers are limited by the Cannabis Act and provincial regulations with respect to offering sales, advertising, location, maximum quantities, and information sharing in an effort to protect public health and safety. The degree these policies influence consumer purchase behavior will help inform regulatory refinement. METHODS: A discrete choice experiment within a cross-sectional online survey was used to explore trade-offs consumers make when deciding where to purchase cannabis. Attributes included availability of sales/discounts, proximity, product information, customer service, product variety, and provincial regulation. Participants ≥ 19 years old who lived in Canada and purchased cannabis in the previous 12 months were recruited through an online market research survey panel. A multinomial logit (MNL) model was used for the base model, and latent class analysis was used to assess preference sub-groups. Key limitations included ordering effect, hypothetical bias, and framing effect. RESULTS: The survey was completed by 1626 people, and the base model showed that customer service carried the most weight in purchase decisions, followed by proximity and availability of sales and discounts. There was considerable heterogeneity in preference patterns, with a five-group latent class model demonstrating best fit. Only one group (15% of sample) placed a high value on the store being provincially regulated, while three groups were willing to make a trade-off with regulation to access better customer service, product information, or closer proximity. One group preferred non-regulated sources (24% of sample); this group was also primarily driven by the availability of sales and discounts. Three groups (60.5% of sample) preferred online stores. CONCLUSION: This study highlighted that there exists significant diversity with respect to the influence of consumer experiences on cannabis purchase behaviors. Modifications to cannabis retail regulations that focus on improving access to product information as well as reviewing limitations on sales and discounts could have the most impact for shifting customers to licensed retailers.

Comparing Preferences for Disease Profiles: A Discrete Choice Experiment from a US Societal Perspective.

OBJECTIVES: There is increasing interest in expanding the elements of value to be considered when making health policy decisions. To help inform value frameworks, this study quantified preferences for disease attributes in a general public sample and examined which combination of attributes (disease profiles) are considered most important for research and treatment. METHODS: A discrete choice experiment (DCE) was conducted in a US general population sample, recruited through online consumer panels. Respondents were asked to select one of a set of health conditions they believed to be most important, characterized by attributes defined by a previous qualitative study: onset age; cause of disease; life expectancy; caregiver requirement; symptom burden (characterized by the Health Utilities Index with varying levels of ambulation independence, dexterity limitations, and degree of pain and discomfort); and disease prevalence. A fractional factorial DCE design was implemented using R, and 60 choice sets were generated (separated into blocks of 10 per participant). Data were analyzed using a mixed-logit regression model, and results used to assess the likelihood of preferring disease profiles. Based on individual attribute preferences, overall preferences for disease profiles, including a profile aligned with Duchenne muscular dystrophy (DMD), were compared. RESULTS: Fifty-two percent of respondents (n = 537) were female, and 70.6% were aged 18-54 years. Attributes considered most important were those related to life expectancy (odds ratio [OR], 95% confidence interval [CI] 1.88 [1.56-2.27] for a 50% reduction in remaining life expectancy vs no impact), and symptom burden (OR [95% CI] 1.84 [1.47-2.31] for severe vs mild burden). Greater importance was also found for pediatric onset, caregiver requirement, and diseases affecting more people. As an example of disease profile preferences, a DMD-like pediatric inherited disease with 50% reduction in life expectancy, extensive caregiver requirement, severe symptom burden, and 1:5000 prevalence had 2.37-fold higher odds of being selected as important versus an equivalent disease with adult onset and no life expectancy reduction. CONCLUSIONS: Of disease attributes included in this DCE, respondents valued higher prevalence of disease, life expectancy and symptom burden as most important for prioritizing research and treatment. Based on expressed attribute preferences, a case study of an inherited pediatric disease involving substantial reductions to length and quality of life and requiring caregiver support has relatively high odds of being identified as important compared to diseases reflecting differing attribute profiles. These findings can help inform expansions of value frameworks by identifying important attributes from the societal perspective.

Asthma-related emergency admissions and associated healthcare resource use in Alberta, Canada.

BACKGROUND: There is a lack of real-world research assessing asthma management following asthma-related emergency department (ED) discharges. The objective of this study was to characterise follow-up care, healthcare resource use (HCRU) and medical costs following ED admissions in Alberta, Canada. METHODS: A retrospective cohort study was conducted on adults with asthma using longitudinal population-based administrative data from Alberta Health Services. Adult patients with asthma and ≥1 ED admission from 1 April 2015 to 31 March 2020 were included. ED admissions, outpatient visits, hospitalisations and asthma-specific medication use were measured in the 30 days before and up to 90 days after each asthma-related ED admission. Mean medical costs attributable to each type of HCRU were summarised. All outcomes were stratified by patient baseline disease severity. RESULTS: Among 128 063 patients incurring a total of 20 142 asthma-related ED visits, a substantial rate of ED readmission was observed, with 10% resulting in readmissions within 7 days and 35% within 90 days. Rates increased with baseline asthma severity. Despite recommendations for patients to be followed up with an outpatient visit within 2-7 days of ED discharge, only 6% were followed up within 7 days. The mean total medical cost per patient was $C8143 in the 30 days prior to and $C5407 in the 30 days after an ED admission. CONCLUSIONS: Despite recommendations regarding follow-up care for patients after asthma-related ED admissions, there are still low rates of outpatient follow-up visits and high ED readmission rates. New or improved multidimensional approaches must be integrated into follow-up care to optimise asthma control and prevent readmissions.

Cost-Effectiveness of Pharmacist Prescribing for Managing Hypertension in the United States.

Importance: Pharmacist-led interventions can significantly improve blood pressure (BP) control. The long-term cost-effectiveness of pharmacist-prescribing interventions implemented on a large scale in the US remains unclear. Objective: To estimate the cost-effectiveness of implementing a pharmacist-prescribing intervention to improve BP control in the US. Design, Setting, and Participants: This economic evaluation included a 5-state Markov model based on the pharmacist-prescribing intervention used in The Alberta Clinical Trial in Optimizing Hypertension (or RxACTION) (2009 to 2013). In the trial, control group patients received an active intervention, including a BP wallet card, education, and usual care. Data were analyzed from January to June 2023. Main Outcomes and Measures: Cardiovascular (CV) events, end-stage kidney disease events, life years, quality-adjusted life years (QALYs), lifetime costs, and lifetime incremental cost-effectiveness ratio (ICER). CV risk was calculated using Framingham risk equations. Costs were based on the reimbursement rate for level 1 encounters, medication costs from published literature, and event costs from national surveys and pricing data sets. Quality of life was determined using a published catalog of EQ-5D utility values. One-way sensitivity analyses were used to assess alternative reimbursement values, a reduced time horizon of 5 years, alternative assumptions for BP reduction, and the assumption of no benefit to the intervention after 10 years. The model was expanded to the US population to estimate population-level cost and health impacts. Results: Assumed demographics were mean (SD) age, 64 (12.5) years, 121 (49%) male, and a mean (SD) baseline BP of 150/84 (13.9/11.5) mm Hg. Over a 30-year time horizon, the pharmacist-prescribing intervention yielded 2100 fewer cases of CV disease and 8 fewer cases of kidney disease per 10 000 patients. The intervention was also associated with 0.34 (2.5th-97.5th percentiles, 0.23-0.45) additional life years and 0.62 (2.5th-97.5th percentiles, 0.53-0.73) additional QALYs. The cost savings were $10 162 (2.5th-97.5th percentiles, $6636-$13 581) per person due to fewer CV events with the pharmacist-prescribing intervention, even after the cost of the visits and medication adjustments. The intervention continued to produce benefits in more conservative analyses despite increased costs as the ICER ranged from $2093 to $24 076. At the population level, a 50% intervention uptake was associated with a $1.137 trillion in cost savings and would save an estimated 30.2 million life years over 30 years. Conclusion and Relevance: These findings suggest that a pharmacist-prescribing intervention to improve BP control may provide high economic value. The necessary tools and resources are readily available to implement pharmacist-prescribing interventions across the US; however, reimbursement limitations remain a barrier.

Drivers of Purchase Decisions Among Consumers of Dried Flower Cannabis Products: A Discrete Choice Experiment.

OBJECTIVE: Cannabis was legalized for nonmedical use in Canada in 2018. However, with a long-established illegal market, it is important to understand cannabis consumers' preferences in order to create a market that encourages purchasing cannabis through legalized channels. METHOD: A survey including a discrete choice experiment was conducted to estimate preference weights for seven attributes of dried flower cannabis purchases (price, packaging, moisture level, potency, product recommendations, package information, and regulation by Health Canada). Participants were at least 19 years of age, lived in Canada, and purchased cannabis in the last 12 months. A multinomial logit (MNL) model was used for the base model, and latent class analyses to identify subgroups preference profiles. RESULTS: A total of 891 participants completed the survey. The MNL model showed that all attributes significantly influenced choice, except product recommendations. Potency and package information were most important. A three-group latent class model showed that about 30% of the sample were most concerned with potency, whereas two groups--jointly making up the remaining 70%--were most concerned with package type (about 40% preferred bulk packaging, and about 30% preferred pre-rolled joints). CONCLUSIONS: Consumer purchase preferences for dried flower cannabis were influenced by different attributes. Preference patterns can be grouped into three categories. About 30% of the population appeared to have their preferences met by the legalized market, whereas another 30% appeared to be more loyal to the unlicensed market. The remaining 40% represented a group that may be influenced through regulatory changes to simplify packaging and increase availability of product information.

Exploring Consumer Preferences for Cannabis Vaping Products to Support Public Health Policy: A Discrete Choice Experiment.

BACKGROUND: Phase two of cannabis legalisation in Canada brought cannabis vaping products to the market. This decision was controversial due to an outbreak of vaping cannabis use-associated lung injury. This resulted in three provinces banning the sale of cannabis vaping products causing inequitable access. This study sought to explore consumer preferences for cannabis vaping products to inform cannabis policy. METHODS: We used a discrete choice experiment to explore consumer preferences for attributes of cannabis vaping products. Attributes included type of device, price, tetrahydrocannabinol (THC) potency, vape liquid content, product recommendations and Health Canada regulation. Participants lived in Canada, were aged ≥ 19 years, and had purchased a cannabis vape in the last 12 months. A multinomial logit (MNL) model was used for the base model, and latent class analysis to assess preference sub-groups. RESULTS: In total, 384 participants completed the survey; the MNL model showed that price and potency were the most important attributes. A three-group latent class model showed that ~ 40% of the sample was driven primarily by Health Canada Regulation and were willing to pay $56 more for a product that was regulated compared to one that was not. About 33% of the sample was driven by price, and 26% was driven by type of device. CONCLUSION: While regulated status by Health Canada was most important to some consumers (~ 40%), nearly 60% of the sample were willing to make trade-offs in regulated status for products with a lower price. Therefore, policymakers need to consider the broader public health implications of banning cannabis vapes in some regions.

Insights from the AQUA Registry: a retrospective study of anticholinergic polypharmacy in the United States.

Background: Anticholinergic (ACH) burden is a risk factor for negative health outcomes among older adults. Several medications contribute to ACH burden, including antimuscarinics used to manage overactive bladder (OAB). Objectives: This study aimed to understand the extent of ACH burden in an OAB population in the United States. Design: Non-interventional retrospective analysis. Methods: Adults with OAB whose care providers participated in the American Urological Association Quality (AQUA) Registry between 2014 and 2020 were included in this study. An adapted version of the Pharmacy Quality Alliance (PQA) measure of anticholinergic polypharmacy (poly-ACH) was used to assess ACH burden. The primary outcome was the annual prevalence of poly-ACH, and a secondary outcome was the percentage of patients taking 0, 1, 2, 3, 4, or ⩾ 5 ACH medications by calendar year. Analyses were stratified by age category at diagnosis and sex. Results: The sample comprised 552,840 patients with OAB. The mean age at initial OAB diagnosis was 65.7 years (58.2% male; 57.4% white). Prevalence of poly-ACH was highest in 2015 (3.7%) and lowest in 2020 (1.9%). Patients prescribed no ACH medications made up the largest proportion of each cohort, while those prescribed five or more comprised the smallest. The trend of decreasing proportions of patients taking increasing numbers of ACH medications was consistent. The proportion of patients prescribed no ACH medications increased from 63.3% in 2014 to 74.6% in 2020. The percentage of those prescribed three or more ACHs remained largely unchanged. Poly-ACH was highest among younger individuals (< 65 years of age) and females; temporal trends were similar overall and within each age and sex stratum. Conclusion: In this study, poly-ACH in patients with OAB was relatively infrequent and decreased over the study period. Further evaluation of poly-ACH is needed to assess whether the study findings reflect increased awareness of the negative effects of poly-ACH.

Health State Utility Mapping of Rimegepant for the Preventive Treatment of Migraine: Double-Blind Treatment Phase and Open Label Extension (BHV3000-305).

INTRODUCTION: The objectives of this study were to (1) report long-term health-related quality of life (HRQoL) outcomes among patients using rimegepant preventatively in BHV3000-305 (NCT03732638) open-label extension (OLE) and (2) map Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2) to EQ-5D-3L utility values over the double-blind treatment (DBT; 0-12 weeks) and the OLE (13-64 weeks) to assess the influence of treatment on these values. METHODS: This was a post hoc analysis using data from a rimegepant study for the prevention of migraine (BHV3000-305). Adult patients with migraine took either rimegepant 75 mg or placebo every other day (EOD) during the DBT phase. All patients received rimegepant during the OLE. MSQv2 was measured at baseline, weeks 12, 24, and 64. A validated algorithm was used to map MSQv2 scores to EQ-5D utilities. RESULTS: Baseline data were available for 347 patients treated with placebo and 348 treated with rimegepant in the DBT period, who continued to the OLE. Baseline EQ-5D utilities were similar between trial arms: 0.598 for placebo and 0.614 for rimegepant. EQ-5D improved from baseline to week 12 and utilities increased by + 0.09 for placebo and + 0.10 for rimegepant (p value = 0.011). By 24 weeks, at which point patients who were originally randomized to placebo had received rimegepant 75 mg EOD for 12 weeks, HRQoL measures (MSQv2 and EQ-5D) were similar across groups, demonstrating rapid onset of treatment effect. This HRQoL improvement was durable out to 64 weeks. CONCLUSION: Compared to placebo, treatment with rimegepant 75 mg was associated with greater improvement in EQ-5D utilities during the 12-week DBT phase. Patients originally randomized to placebo experienced a similar improvement in EQ-5D utilities after switching to rimegepant during the OLE, demonstrating that benefits are realized within 12 weeks of active treatment. This preventive effect was durable out to 64 weeks and was associated with an additional increase in HRQoL over time. TRIAL REGISTRATION: NCT03732638.

SABA use as an indicator for asthma exacerbation risk: an observational cohort study (SABINA Canada).

Background: Patients with asthma use short-acting ß-agonists (SABA) to relieve symptoms but SABA alone does not treat underlying inflammation. Thus, over-reliance on SABA may result in poor asthma control and negative health outcomes. Objective: To describe use of SABA and characterise the relationship with severe exacerbations in the Canadian provinces of Nova Scotia (NS) and Alberta (AB). Methods: In this longitudinal Canadian SABA In Asthma (SABINA) study, patients with an asthma diagnosis were identified between 2016 and 2020 within two provincial administrative datasets (Health Data Nova Scotia and Alberta Health Services). All patients were followed for ≥24 months, with the first 12 months used to measure baseline asthma severity. Medication use and the relationship of SABA overuse (three or more canisters per year) with severe asthma exacerbations were characterised descriptively and via regression analysis. Results: A total of 115 478 patients were identified (NS: n=8034; AB: n=107 444). SABA overuse was substantial across both provinces (NS: 39.4%; AB: 28.0%) and across all baseline disease severity categories. Patients in NS with SABA overuse had a mean±sd annual rate of 0.46±1.11 exacerbations, compared to 0.30±1.36 for those using fewer than three canisters of SABA. Patients in AB had mean±sd exacerbation rates of 0.31±0.86 and 0.17±0.62, respectively. The adjusted risk of severe exacerbation was associated with SABA overuse (NS: incidence ratio rate 1.36, 95% CI 1.18-1.56; AB: incidence ratio rate 1.32, 95% CI 1.27-1.38). Conclusion: This study supports recent updates to Canadian Thoracic Society and Global Initiative for Asthma guidelines for asthma care. SABA overuse is associated with increased risk of severe exacerbations and can be used to identify patients at a higher risk for severe exacerbations.

Rimegepant, Ubrogepant, and Lasmiditan in the Acute Treatment of Migraine Examining the Benefit-Risk Profile Using Number Needed to Treat/Harm.

OBJECTIVES: To develop and compare benefit-risk profiles for rimegepant, ubrogepant, and lasmiditan based on a network meta-analysis (NMA) of published clinical trials. METHODS: A fixed-effects Bayesian NMA of randomized controlled trials of lasmiditan, rimegepant, and ubrogepant for the acute treatment of adults with migraine were used to determine risk differences for efficacy and safety outcomes of the 3 treatments compared with pooled placebo. Risk differences were used to calculate number needed to treat (NNT) for pain relief and pain freedom at 2 and 2 to 24 hours and freedom from most bothersome symptoms at 2 hours; and number needed to harm (NNH) for dizziness and nausea, relative to placebo. RESULTS: Results were based on 5 randomized controlled trials (NCT03461757, NCT02828020, NCT02867709, NCT02439320, and NCT02605174). NNT to achieve sustained pain relief at 2 to 24 hours was lowest for rimegepant 75 mg (5; 95% credible interval [Crl]: 4, 7) and ubrogepant 100 mg (5; 95% Crl: 4, 8) and highest for ubrogepant 25 mg (8; 95% Crl: 5, 16). Rimegepant had the lowest NNT to achieve sustained pain freedom at 2 to 24 hours and lasmiditan 50 mg had the highest (7; 95% Crl: 5, 12 vs. 26; 95% Crl: 13, 95). NNH for dizziness and nausea was highest for ubrogepant 25 mg (28; 95% Crl: 15, 62 and 99; 95% Crl: -2580, 2378, respectively). Lasmiditan 200 mg had the lowest NNH for dizziness and rimegepant 75 mg had the lowest NNH for nausea. CONCLUSIONS: The benefit-risk profiles of lasmiditan, rimegepant, and ubrogepant may improve clinical decision-making.

An Epidemiological Model to Estimate the Prevalence of Diffuse Large B-Cell Lymphoma in the United States.

BACKGROUND: Prevalence is reflective of disease incidence and survival, and defined as the number of patients living with active disease. In diseases such as diffuse large B-cell lymphoma (DLBCL) with treatments with curative potential, a proportion of patients are cured, leading to a need for accurate, contemporary estimates of DLBCL prevalence to gauge the impact of the rapidly emerging treatment landscape. METHODS: Data from Surveillance, Epidemiology, and End Results (SEER) from 2000-2018 were utilized to develop an epidemiological model of incidence, survival, and cure, to estimate the current prevalent DLBCL population requiring active management in the United States (US). A variety of estimates were explored regarding cure rate and timing, based on a companion analysis of MarketScan data for treatment patterns and survival in incident DLBCL patients, and conditional survival analysis of SEER data. RESULTS: Across scenarios, with estimated cure ranging from 52.8% and 68.9%, and timing of cure ranging from 1 and 20 years post diagnosis, the estimated prevalence ranged from 63,883 to 142,889. With an assumption of no cure, estimated prevalence was 179,475. DISCUSSION: Prevalence estimates of DLBCL varied almost 3-fold, depending on specific cure adjustments made. Further understanding of DLBCL prevalence, for newly diagnosed and relapsed and/or refractory disease, is important to characterize the impact of emerging treatment options and related health care burden.

A stated preference survey to explore patient preferences for novel preventive migraine treatments.

OBJECTIVE: The objective of this study was to explore patient preference for attributes of calcitonin gene-related peptide (CGRP) inhibitors for the preventive treatment of migraine and to describe differences in treatment preferences between patients. BACKGROUND: CGRP inhibitors are a novel class of migraine drugs specifically developed for the preventive treatment of migraine. Clinicians should understand patient preferences for CGRP inhibitors to inform and support prescribing choices. METHODS: Patients with migraine in the US and Germany were recruited to participate in an online discrete choice experiment (DCE) survey, which presented hypothetical treatment choices using five attributes: mode of administration, side effects, migraine frequency, migraine severity, and consistency of treatment effectiveness. Attribute selection was informed by a literature review and semi-structured patient interviews (n = 35), and evaluated using patient cognitive debriefing interviews (n = 5). RESULTS: Of 680 who consented to participate, 506 participants completed the survey and were included in the study (US = 257; Germany = 249). Overall, participants placed highest importance (preference weight, beta = 1.65, p < 0.001) on the treatment's ability to reduce the severity of migraine (mild vs. unchanged severity), followed by consistent treatment effectiveness (beta = 1.13, p < 0.001), and higher chance of reduced migraine frequency (beta = 1.00, p < 0.001). Participants preferred an oral tablet every other day (beta = 1.00, p < 0.001) over quarterly infusion, quarterly injections (p = 0.019), or monthly injection (p < 0.001). Preference for all treatment attributes were heterogeneous, and the subgroup analyses found that participants naïve to CGRP monoclonal antibody treatments had a stronger preference for oral therapy compared to those with such experience (p = 0.006). CONCLUSION: In this DCE assessing CGRP inhibitors attributes, the main driver of patient choice was treatment effectiveness, specifically reduced migraine severity, and consistent treatment effectiveness. Further, patients exhibited an overall preference for an oral tablet every other day over injectables. Patients' experience with previous treatments informs the value they place on treatment characteristics.

Measuring interictal burden among people affected by migraine: a descriptive survey study.

BACKGROUND: Previous research has extensively documented the impact of migraine episodes ('ictal') on patients' health-related quality of life. Few studies have looked at the impact of migraine on migraine-free days ('interictal'). This study was designed to describe interictal burden of migraine in a mixed group of people affected by migraine and to explore patient characteristics associated with interictal burden. METHODS: People with migraine in the United States (US) and Germany were recruited for a cross-sectional online survey, including a subgroup treated with calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb). The survey included the Migraine Interictal Burden Scale (MIBS-4), Headache Impact Test (HIT-6), and items measuring patient demographics, clinical and treatment background. Data were analyzed using descriptive statistics and linear regression. RESULTS: Five hundred six people with migraine completed the survey (US: n = 257; Germany: n = 249), of whom 195 had taken a CGRP mAb for three or more months. Participants had a mean of 8.5 (SD = 6.4) Monthly Migraine Days (MMD) and 10.4 (SD = 7.1) Monthly Headache Days (MHD). The mean MIBS-4 score was 6.3 (SD = 3.4), with 67% reporting severe interictal burden (MIBS-4: ≥5). The mean HIT-6 score was 65.3 (SD = 6.0), with 86% reporting severe migraine impact (HIT-6: ≥60). MIBS-4 was correlated with the HIT-6 (r = 0.37), MMD and MHD (both r = 0.27). The HIT-6, MMD, MHD, CGRP mAb treatment, and depression all had an independent positive association with the MIBS-4. CONCLUSION: Two-thirds of the study sample reported substantial interictal burden. Whilst interictal burden was associated with migraine frequency and impact of migraine attacks, study results also show it represented a distinct aspect of the overall disease burden. Study findings further indicate unique associations between interictal burden and depression. A unique positive association between interictal burden and CGRP mAb treatment suggests a remaining unmet need among people affected by migraine treated with CGRP mAb.

The cost-effectiveness of abobotulinumtoxinA (Dysport) and onabotulinumtoxinA (Botox) for managing spasticity of the upper and lower limbs, and cervical dystonia.

OBJECTIVE: To evaluate the costs and benefits associated with the use of abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) for lower limb spasticity in children, upper and lower limb spasticity in adults, and cervical dystonia in adults. METHODS: This pharmacoeconomic analysis compared aboBoNT-A with onaBoNT-A. A decision tree model with a 1-year time horizon was conducted from a UK National Health Service (NHS) perspective using data from a variety of sources: randomized controlled trials (RCTs), network meta-analyses (NMAs), observational studies, and a physician survey investigating treatment patterns and resource utilization. Four patient populations were included: pediatric patients with lower limb spasticity (PLL), and adults with upper limb spasticity (AUL), lower limb spasticity (ALL), and cervical dystonia (CD). Outcomes included costs, quality-adjusted life years (QALYs) gained, cost per responder, and incremental cost per QALY gained. The effectiveness of each treatment was evaluated as a response to treatment. The base case assumption was that all patients in the model continued to receive botulinum toxin type A (BoNT-A) treatments at regular intervals regardless of treatment response status. Scenario analysis evaluated the impact of discontinuing BoNT-A for patients without a response to the first injection. RESULTS: The model found that aboBoNT-A resulted in greater quality-of-life and lower costs compared with onaBoNT-A for the management of spasticity and CD in all included indications. Across populations, cost savings ranged from £304 to £3,963 and QALYs gained ranged from 0.010 to 0.02 over a 1-year time horizon. Results were robust to scenario analyses and were driven by the impact of treatment response on health-related quality-of-life. CONCLUSIONS: AboBoNT-A was associated with higher treatment response, improved quality-of-life, and reduced costs in spasticity and CD versus onaBoNT-A. These findings could help deliver more effective and efficient healthcare in the NHS.

The objective of this study was to compare the costs and health outcomes associated with abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox) for treating children and adults with a variety of conditions related to limb spasticity and cervical dystonia. Therapies such as aboBoNT-A and onaBoNT-A have been shown to reduce spasticity, deformity, pain, and cervical dystonia symptoms. They can also improve function, movement, and self-care abilities. We estimated the treatment costs for patients with spasticity and patients with cervical dystonia receiving aboBoNT-A and onaBoNT-A in the UK. We also estimated other health-related costs that patients were expected to incur while receiving these treatments, as well as their quality of life.For each indication (spasticity in the upper and lower limbs in adults and children, cervical dystonia in adults), research studies were identified to estimate the likelihood of patient response for aboBoNT-A and onaBoNT-A. Survey studies were assessed to understand use of health services and costs for patients who respond to therapy vs. those who do not. We estimated total costs over one year and expected quality of life for patients. Costs included the costs of aboBoNT-A and onaBoNT-A treatments, as well as other health services.In all identified studies, the likelihood of response was higher for aboBoNT-A than for onaBoNT-A. This was associated with reduced need for other health services (and therefore lower costs), and better quality of life for patients receiving aboBoNT-A. In addition, the cost per year of aboBoNT-A treatment was lower than onaBoNT-A treatment for all indications. Therefore, treatment with aboBoNT-A was consistently associated with lower costs and better quality of life. This outcome is referred to as "economically dominant," meaning that from a health economic perspective, aboBoNT-A would be preferred to onaBoNT-A for treating patients with spasticity or cervical dystonia.

Real-World experience of interictal burden and treatment in migraine: a qualitative interview study.

BACKGROUND: The debilitating nature of migraine attacks is widely established; however, less is known about how the interictal burden (i.e., how patients are affected in-between migraine episodes) of migraine impacts on patients' health-related quality of life (HRQL). Acute and preventive treatments may lift the burden of the disease, but they often have unwanted side effects and limited effectiveness. The objective of this study was to understand the interictal burden of migraines, from the patient perspective, and to explore patient experience with migraine treatments. METHODS: Participants (n=35) with a self-reported diagnosis of migraine were recruited in the US, UK and Canada, including a subgroup of patients who had taken calcitonin gene-related peptide monoclonal antibody (CGRP mAb) treatment for at least three months. Participants completed a background questionnaire, followed by a semi-structured interview via telephone or video call. The interviews explored patients' migraine symptoms, perception of interictal burden and treatment experience. The interview transcripts were analysed using thematic analysis. RESULTS: The most reported migraine symptom was migraine pain, followed by aura, sensory sensitivity and nausea. Most participants reported interictal impact on HRQL, lifestyle changes they made to avoid triggers or in anticipation of an attack, impacts on work, career, daily activities and relationships. Emotional impacts were reported by all participants, including anger, depression, anxiety and hopelessness. Many participants who took preventive treatments reported improvements in HRQL and functioning but still experienced breakthrough attacks. Among patients who took CGRP mAbs, participants noted varying consistency of treatment effectiveness between treatment administrations. CONCLUSION: This study detailed the additional HRQL impact of migraine in-between migraine attacks and described the unmet need for effective treatment options to prevent and mitigate migraine attacks.

A Method for Reconstructing Individual Patient Data From Kaplan-Meier Survival Curves That Incorporate Marked Censoring Times.

Introduction. Access to individual patient data (IPD) can be advantageous when conducting cost-effectiveness analyses or indirect treatment comparisons. While exact times of censoring are often marked on published Kaplan-Meier (KM) curves, an algorithm for reconstructing IPD from such curves that allows for their incorporation is presently unavailable. Methods. An algorithm capable of incorporating marked censoring times was developed to reconstruct IPD from KM curves, taking as additional inputs the total patient count and coordinates of the drops in survival. The reliability of the algorithm was evaluated via a simulation exercise, in which survival curves were simulated, digitized, and then reconstructed. To assess the reliability of the reconstructed curves, hazard ratios (HRs) and quantiles of survival were compared between the original and reconstructed curves, and the reconstructed curves were visually inspected. Results. No systematic differences were found in HRs and quantiles in the original versus reconstructed curves. Upon visual inspection, the reconstructed IPD provided a close fit to the digitized data from the published KM curves. Inherent to the algorithm, censoring times were incorporated into the reconstructed data exactly as specified. Conclusion. This new algorithm can reliably be used to reconstruct IPD from reported KM survival curves in the presence of extractable censoring times. Use of the algorithm will allow health researchers to reconstruct IPD more closely by incorporating censoring times exactly as marked, requiring as additional inputs the total patient count and coordinates of the drops in survival.