Background
Chronic migraine (CM) and episodic migraine (EM) are associated with substantial headache-related disability, poor quality of life and global societal burden. In this subgroup analysis ...from the CONQUER study, we report efficacy outcomes from a pre-specified analysis of galcanezumab versus placebo in patients with CM or EM and 3–4 prior preventive medication category failures due to inadequate efficacy (after at least 2 months at maximum tolerated dose), or safety or tolerability reasons. The patient population is of particular interest due to evidence of decreased quality of life and increased economic burden among patients with migraine that is inadequately managed and is of interest to decision-makers globally.
Methods
Key outcomes included overall mean change from baseline in monthly migraine headache days and proportions of patients achieving ≥30% (CM), ≥50%, and ≥ 75% reduction (response rates) in monthly migraine headache days across Months 1–3. Patient functioning and disability were evaluated at Month 3.
Results
Of the 462 randomized patients, 186 (40.3%) had a history of 3–4 preventive category failures. Galcanezumab versus placebo resulted in significantly (
P
≤ .001) larger overall mean reduction in monthly migraine headache days (total: − 5.49 versus − 1.03; CM: − 6.70 versus − 1.56; EM: − 3.64 versus − 0.65). Similarly, the ≥50% response rate was significantly (
P
≤ .001) higher with galcanezumab versus placebo (total: 41.0 versus 12.7; CM: 41.5 versus 8.4; EM: 41.1 versus 16.5). In the CM group, the ≥30% response rate was significantly higher in the galcanezumab group than the placebo group (CM, 57.5 versus 19.8,
P
≤ .0001) as was the ≥75% response rate (13.3 versus 2.6,
P
≤ .05). Galcanezumab also resulted in significant (
P
< .0001) improvements in patient functioning and reductions in disability.
Conclusions
Galcanezumab was effective in a difficult-to-treat population of patients with CM or EM who had failed 3–4 prior preventive medication categories.
Trial registration
CONQUER. Clinicaltrials.gov identifier:
NCT03559257
.
Purpose: To evaluate patient-reported outcomes (PROs) among patients with migraine, including those who were preventive-naive and preventive-treated. Methods: This was a point-in-time, real-world ...study of patients with migraine in the US and EU5 (France, Germany, Spain, Italy, and UK) and their physicians using data from the Adelphi Migraine Disease Specific Programme (DSPTM). Physicians completed patient record forms (PRFs) for the next nine consulting patients with migraine plus a tenth patient, who did not need to be consecutive, for whom prior preventive migraine treatments had failed at least once, in order to achieve oversampling of such patients. Patients were given self-completion (PSC) forms that included the Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ), Migraine Disability Assessment Scale (MIDAS), and Work Productivity and Activity Impairment (WPAI) questionnaire. Populations of interest included preventive-naive and preventive-treated patients defined by the number of treatment lines (1-2 or 3+ preventive regimens). Continuous variables were compared using ftest or ANOVA if normally distributed and Mann-Whitney if not. Chi-squared was used for categorical variables. Results: During August-December 2017, 615 physicians (359 PCPs, 256 neurologists) completed PRFs for 5785 patients (71% female; mean age 40 (+ or - 14) years; 65% in full- or part-time employment). Of these, 2798 completed a PSC (preventivenaive/1-2/3+ preventive lines, n=1707/1034/57). Preventive-treated patients had a greater patient-reported burden across multiple measures versus preventive-naive patients. Preventive-treated patients had lower MSQ scores indicating greater functional impairment, higher MIDAS scores indicating greater migraine-associated disability, and higher WPAI scores indicating greater overall work and activity impairment than preventive-naive patients. The magnitude of difference was greatest for the 3+ preventive-treatments cohort. Patterns were similar in the US and EU5. Conclusion: Among patients with migraine who are preventive-treated, including those with multiple lines of therapy, there remain considerable unmet needs in terms of restoring patient function. Keywords: migraine, preventive, patient-reported outcomes, real-world
Obtaining reliable estimates of the health-related quality of life (HR-QoL) of people with predementia Alzheimer's disease AD (preclinical or prodromal AD), mild cognitive impairment (MCI) and ...dementia is essential for economic evaluations of related health interventions.
To provide an overview of which quality of life instruments are being used to assess HR-QoL in people with predementia AD, MCI or dementia; and, to summarise their reported HR-QoL levels at each stage of the disease and by type of respondent.
We systematically searched for and reviewed eligible studies published between January 1990 and the end of April 2017 which reported HR-QoL for people with predementia AD, MCI or dementia. We only included instruments which are preference-based, allowing index scores/utility values to be attached to each health state they describe based on preferences obtained from population surveys. Summary results were presented by respondent type (self or proxy), type of instrument, geographical location and, where possible, stage of disease. Health state utility values derived using the EuroQoL 5-Dimensions (EQ-5D) were meta-analysed by pooling reported results across all studies by disease severity (MCI, mild, mild to moderate, moderate, severe dementia, not specified) and by respondent (person with dementia, carer, general public, not specified), using a fixed-effects approach.
We identified 61 studies which reported HR-QoL for people with MCI or dementia using preference-based instruments, of which 48 used the EQ-5D. Thirty-six studies reported HR-QoL for mild and/or moderate disease severities, and 12 studies reported utility values for MCI. We found systematic differences between self-rated and proxy-rated HR-QoL, with proxy-rated utility valued being significantly lower in more severe disease states.
A substantial literature now exists quantifying the impact of dementia on HR-QoL using preference-based measures, giving researchers and modellers a firmer basis on which to select appropriate utility values when estimating the effectiveness and cost-effectiveness of interventions in this area. Further research is required on HR-QoL of people with preclinical and prodromal AD and MCI, possible differences by type of dementia, the effects of comorbidities, study setting and the informal caregiver's own HR-QoL, including any effect of that on their proxy-ratings.
Background
Migraine has a severe impact on health-related quality of life (HRQoL) affecting physical, emotional, and social aspects of daily living of an individual. Preventive treatment has been ...demonstrated to improve HRQoL by reducing the frequency of migraine headache days.
Methods
The study used data from 2017 Adelphi Migraine Disease Specific Program, which is a cross-sectional survey of physicians and their consulting patients with migraine in the United States (US) and five European countries (EU Germany, France, UK, Italy and Spain). Objectives were to evaluate patient-reported outcome (PRO) measures in the following two subgroups and by region (US and EU): (i) patients who are eligible for migraine preventive treatment (≥4 migraine headache days/month), and (ii) patients who are non-eligible for preventive treatment (< 4 migraine headache days/month). Patient-reported outcome measures that were assessed included the following: Migraine-Specific Quality-of-Life Questionnaire Version 2.1, Migraine Disability Assessment Scale (MIDAS), European Quality of Life-5 Dimensions-5 Levels version, and Work Productivity and Activity Impairment.
Results
In total, 5462 patients (US = 1373; EU = 4089) were included in the study (preventive eligible: US = 584; EU = 1942; preventive non-eligible: US = 789; EU = 2147). In the US and EU, preventive eligible patients were significantly more likely to have worse disability as measured by MIDAS than non-eligible patients; preventive eligible patients also had significantly greater functional impairment, worse health utility, and overall greater work impairment (
p
< 0.0001). Among patients who were preventive eligible, a larger proportion of patients in the US reported that migraine forced them to reduce the number of hours worked as compared with the EU population (29.0% vs 24.7%).
Conclusion
Patients who were preventive eligible (≥4 migraine headache days/month) demonstrated greater burden of disease across multiple PRO measures; trends were similar across the US and the five EU countries.
Objective:
The efficacy of galcanezumab was evaluated in patients with episodic cluster headache and history of preventive treatment failure.
Methods:
In the randomized, 8-week, double-blind study ...(CGAL), patients with episodic cluster headache received once-monthly subcutaneous injections of galcanezumab 300 mg or placebo. Patients who completed CGAL and enrolled in an open-label study were queried for preventive treatment history. In a subset of patients with a known history of failure of verapamil or any other prior preventive treatment, a post hoc analysis of least square mean change from baseline in weekly cluster headache attack frequency across Weeks 1 to 3 was assessed.
Results:
Fifteen patients provided data for known history of prior preventive treatment failure (6 placebo, 9 galcanezumab), of whom 11 failed verapamil. The mean reduction in the weekly frequency of cluster headache attacks was greater with galcanezumab compared to placebo among patients with prior preventive treatment failure (8.2 versus 2.4); mean difference 5.8 (95% confidence interval CI 2.0, 13.6) and among patients with verapamil failure (10.1 versus 1.6); mean difference 8.5 (95% CI 0.4, 16.7).
Conclusion:
In this exploratory analysis of patients with a known history of prior preventive treatment failures, treatment with galcanezumab resulted in greater mean reductions in weekly cluster headache attacks compared with placebo.
ClinicalTrials.gov:
NCT02397473 (I5Q-MC-CGAL)
NCT02797951 (I5Q-MC-CGAR)
Introduction
Self-injectable calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) auto-injectors and non-CGRP oral medications are currently available for migraine prevention in Japan. ...This study elicited the preferences for self-injectable CGRP mAbs and non-CGRP oral medications and determined differences in the relative importance of auto-injector attributes for patients and physicians in Japan.
Methods
Japanese adults with episodic (EM) or chronic (CM) migraine and physicians who treat migraine completed an online discrete choice experiment (DCE), asking participants to choose a hypothetical treatment they preferred between two self-injectable CGRP mAb auto-injectors and a non-CGRP oral medication. The treatments were described by seven treatment attributes, with attribute levels varying between questions. DCE data were analyzed using a random-constant logit model to estimate relative attribution importance (RAI) scores and predicted choice probabilities (PCP) of CGRP mAb profiles.
Results
A total of 601 patients (79.2% with EM, 60.1% female, mean age: 40.3 years) and 219 physicians (mean length of practice: 18.3 years) completed the DCE. About half (50.5%) of patients favored CGRP mAb auto-injectors, while others were skeptical of (20.2%) or averse (29.3%) to them. Patients most valued needle removal (RAI = 33.8%), shorter injection duration (RAI = 32.1%), and auto-injector base shape and need for skin pinching (RAI = 23.2%). Most physicians (87.8%) favored auto-injectors over non-CGRP oral medications. Physicians most valued less-frequent dosing RAI = 32.7%), shorter injection duration (30.4%), and longer storage outside the fridge (RAI = 20.3%). A profile comparable to galcanezumab showed a higher likelihood of being chosen by patients (PCP = 42.8%) than profiles comparable to erenumab (PCP = 28.4%) and fremanezumab (PCP = 28.8%). The PCPs of the three profiles were similar among physicians.
Conclusion
Many patients and physicians preferred CGRP mAb auto-injectors over non-CGRP oral medications and preferred a treatment profile similar to galcanezumab. Our results may encourage physicians in Japan to consider patient preferences when recommending migraine preventive treatments.
Many patients who require migraine preventive treatment have not been able to tolerate or have not responded to multiple previous preventive medications. We aimed to assess the safety and efficacy of ...galcanezumab, an antibody to calcitonin gene-related peptide, in patients with migraine who had not benefited from preventive medications from two to four categories.
CONQUER was a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial done at 64 sites (hospitals, clinics, or research centres) in 12 countries (Belgium, Canada, Czech Republic, France, Germany, Hungary, Japan, the Netherlands, South Korea, Spain, the UK, and the USA). Patients were 18–75 years of age, with episodic or chronic migraine, with migraine onset before the age of 50 years, who had a documented failure of preventive medications from two to four drug categories in the past 10 years owing to lack of efficacy or tolerability, or both. Patients were randomised 1:1 to receive subcutaneous placebo or galcanezumab 120 mg per month (with a 240 mg loading dose administered as two 120 mg injections) for 3 months. For masking purposes, patients receiving placebo also received two injections during the first dosing visit. Randomisation was done by a computer-generated random sequence by means of an interactive web-response system stratified by country and migraine frequency (low frequency episodic migraine, four to fewer than eight migraine headache days per month; high frequency episodic migraine, eight to 14 migraine headache days per month and fewer than 15 headache days per month; chronic migraine, at least eight migraine headache days per month and at least 15 headache days per month). The primary endpoint was the overall mean change from baseline in number of monthly migraine headache days during the 3-month treatment period in all patients who were randomly assigned and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03559257, and is now completed.
Between Sept 10, 2018, and March 21, 2019, 462 participants with episodic (269 58%) or chronic (193 42%) migraine were randomly assigned and received at least one injection with placebo (n=230) or galcanezumab (n=232). Galcanezumab-treated patients had significantly greater reduction in migraine headache days versus placebo across months 1–3. The galcanezumab group had on average 4·1 fewer monthly migraine headache days compared with baseline (13·4), while the placebo group had on average 1·0 fewer than at baseline (13·0; between-group difference −3·1 95% CI −3·9 to −2·3; p<0·0001; effect size=0·72). Types and number of treatment-emergent adverse events were similar between galcanezumab and placebo. Treatment-emergent adverse events were reported in 122 (53%) of 230 patients in the placebo group and 119 (51%) of 232 patients in the galcanezumab group. There were four serious adverse events during the study, two (1%) reported in the placebo group and two (1%) reported in the galcanezumab group.
Galcanezumab was superior to placebo in the preventive treatment of migraine and was safe and well tolerated in patients for whom multiple previous standard-of-care preventive treatments had failed. Galcanezumab might represent an important treatment option for patients who have not benefited from or tolerated previous standard-of-care treatments.
Eli Lilly.
To identify, in caregivers of patients with Alzheimer's disease (AD) dementia, factors associated with subjective (personal, physical, emotional, and social) and objective (informal caregiver time ...and costs) caregiver burden.
Prospective longitudinal European observational study: post-hoc analysis.
Clinic.
Community-dwelling patients in France and Germany aged ≥ 55 years (n = 969) with probable AD and their informal caregivers.
Mini-Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), 12-item Neuropsychiatric Inventory (NPI-12), Zarit Burden Interview (ZBI), informal caregiver basic and instrumental ADL hours (Resource Utilization in Dementia instrument), and informal caregiver costs. Mixed-effect models of repeated measures (MMRM) were run, including baseline and time-dependent covariates (change from baseline CFB to 18 months in MMSE, ADCS-ADL, and NPI-12 scores) associated with CFB in ZBI score/informal caregiver time over 36 months (analyzed using linear regression models) and informal caregiver costs over 36 months (analyzed using generalized linear models).
Greater decline in patient function (ADCS-ADL) over 18 months was associated with increased subjective caregiver burden (ZBI), hours, and costs over 36 months. Increased behavioral problems (NPI-12) over 18 months also negatively impacted ZBI. Cognitive decline (MMSE) over 18 months did not affect change in caregiver burden.
Long-term informal caregiver burden was driven by worsening functional abilities and behavioral symptoms but not cognitive decline, over 18 months in community-dwelling patients with AD dementia. Identifying the drivers of caregiver burden could highlight areas in which interventions may benefit both caregivers and patients.
To describe clinical characteristics and regional treatment patterns of episodic cluster headache (CH).
A point-in-time survey of physicians and their patients with CH was conducted in the United ...States, United Kingdom and Germany in 2017.
Overall, 1012 patients with episodic CH were analyzed. Demographic and clinical findings were generally consistent across regions. Most patients were men (66.6%) and the mean age was 40.9 years. The greatest proportion of patients (38.3%) had ≤1 attack per day. The mean number of attacks per day (APD) was 2.4 and mean number of cluster periods per year was 2.6; the mean cluster period duration was 30.8 days. Most patients (69.3%) did not report a specific or predicable time when cluster periods occurred. Acute treatment was prescribed for 47.6% of patients, 10.3% of patients received preventive treatment, and 37.9% of patients received combined acute and preventive treatment; 4.2% of patients were not receiving treatment. Frequently prescribed acute treatments were sumatriptan, oxygen, and zolmitriptan; oxygen use varied considerably across countries and was prescribed least often in the United States. Frequently prescribed preventive treatments were verapamil, topiramate, and lithium. Lack of efficacy and tolerability were the most common reasons for discontinuing preventive treatment.
We observed high use of acute treatments, but only half of patients used preventive treatments despite experiencing several cluster periods per year with multiple cluster APD. Further studies about the need for and benefits of preventive treatment for episodic CH are warranted.
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