Pooled Subject-Reported Outcomes From 2 Phase 3 Studies of OnabotulinumtoxinA for Simultaneous Treatment of Forehead and Glabellar Lines.

BACKGROUND: Understanding the subjects' perspective is critical for successfully treating upper facial lines. OBJECTIVE: To understand subjects' self-perception and overall satisfaction after onabotulinumtoxinA treatment for forehead and glabellar lines. METHODS: This analysis pooled data from two 12-month, pivotal phase 3 studies in which toxin-naive subjects received onabotulinumtoxinA 40 U or placebo for treatment of upper facial lines. OnabotulinumtoxinA was administered as 0.1-mL injections at 10 prespecified sites (frontalis: 20 U; glabellar complex: 20 U). Each study used 3 reliable and validated patient-reported outcome instruments to evaluate subject satisfaction and appearance-related psychological effects: the Facial Line Satisfaction Questionnaire (FLSQ), the Facial Line Outcomes (FLO-11) Questionnaire, and the Self-Perception of Age (SPA) Questionnaire. In total, data for 865 subjects (608, onabotulinumtoxinA 40 U; 257, placebo) were analyzed. RESULTS: Treatment with onabotulinumtoxinA 40 U resulted in significant and sustained improvements across all pooled FLO-11 items and FLSQ items compared with placebo. SPA results demonstrated that a significant proportion of subjects in the pooled analysis felt they looked younger after treatment than at baseline (all, p < .0001 vs placebo). CONCLUSION: This study demonstrates a high level of treatment satisfaction and significantly improved appearance-related psychological outcomes among toxin-naive subjects after onabotulinumtoxinA 40 U treatment.

Family Impact of Migraine: Development of the Impact of Migraine on Partners and Adolescent Children (IMPAC) Scale.

OBJECTIVE: To describe the development of the Impact of Migraine on Partners and Adolescent Children (IMPAC) scale. BACKGROUND: Although existing data and clinical experience suggest that the impact of migraine is pervasive and extends beyond the individual with migraine, no validated tools exist for assessing the impact of migraine on the family. METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a longitudinal study of people with migraine in the United States. The Family Burden Module (FBM) of the CaMEO Study contained an item pool of 53 questions derived through literature review, clinician input, and patient focus groups pertaining to the following concepts: impact of migraine on family interpersonal relationships, activities, well-being, finances, and health-related quality of life. Respondents with migraine (ie, probands) were categorized into 4 groups based on household composition: migraine probands with partners/spouses and children (M-PC), migraine probands with partners/spouses only (M-P), migraine probands with child(ren) only (M-C), and migraine probands without a partner/spouse or child(ren) (M-O). The IMPAC scale was developed in 3 steps: (1) exploratory factor analysis and item reduction, (2) bifactor analysis, confirmatory factor analysis, and scoring, and (3) reliability and construct validity analyses. RESULTS: The analysis of data from 13,064 respondents to the FBM meeting criteria for migraine yielded a 12-item IMPAC scale, with 4 items applying to all of the groups, 4 more items applying to the groups with partners (M-P and M-PC), and 4 additional items to the groups with children (M-C and M-PC). Item responses can be summed and converted into a scoring system assessing mild (<0.5 SD below mean; IMPAC scale Grade I), moderate (0.5 SD below to <0.5 SD above mean; Grade II), severe (0.5-<1.5 SD above mean; Grade III), and very severe (≥0.5 SD above mean; Grade IV) family impact. Test information curves relating to the IMPAC scale for each household type indicated adequate reliability across a large range of family burden severity (from ∼1 SD below to ∼3 SD above mean) and IMPAC scores showed moderate-to-large correlations with other validated tools (range, ± 0.38-0.52), providing support for construct validity. CONCLUSIONS: We developed a questionnaire to assess family burden attributed to migraine that is brief, robust, and psychometrically sound, with a simple scoring algorithm that can be applied to various household compositions. This questionnaire may be valuable in research settings to provide quantifiable data on the impact of migraine on family dynamics and in clinical settings to facilitate conversations about family burden as a target and a motivation for better treatment.

Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: A retrospective claims analysis.

Background Migraine prevention guidelines recommend oral prophylactic medications for patients with frequent headache. This study examined oral migraine preventive medication (OMPM) treatment patterns by evaluating medication persistence, switching, and re-initiation in patients with chronic migraine (CM). Methods A retrospective US claims analysis (Truven Health MarketScan® Databases) evaluated patients ≥18 years old diagnosed with CM who had initiated an OMPM between 1 January, 2008 and 30 September, 2012. Treatment persistence was measured at six and 12 months' follow-up. Time-to-discontinuation was assessed for each OMPM and compared using Cox regression models. Among those who discontinued, the proportion that switched OMPMs within 60 days or re-initiated treatment between 61 to 365 days, and their associated persistence rates, were also assessed. Results A total of 8707 patients met the inclusion/exclusion criteria. Persistence to the initial OMPM was 25% at six months and 14% at 12 months. Based on Kaplan-Meier curves, a sharp decline of patients discontinuing was observed by 30 days, and approximately half discontinued by 60 days. Similar trends in time-to-discontinuation were seen following the second or third OMPM. Amitriptyline, gabapentin, and nortriptyline had significantly higher likelihood of non-persistence compared with topiramate. Among patients who discontinued, 23% switched to another prophylactic and 41% re-initiated therapy within one year. Among patients who switched, persistence was between 10 to 13% and among re-initiated patients, persistence was between 4 to 8% at 12 months. Conclusions Persistence to OMPMs is poor at six months and declines further by 12 months. Switching between OMPMs is common, but results indicate that persistence worsens as patients cycle through various OMPMs.

OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine over one year of treatment: Pooled results from the PREEMPT randomized clinical trial program.

BACKGROUND: Chronic migraine (CM) is associated with high impact and reduced health-related quality of life (HRQoL). METHODS: Patients with CM from PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) were randomized (1:1) to receive onabotulinumtoxinA or placebo for two 12-week cycles in the double-blind (DB) phase, followed by three 12-week cycles of open-label (OL) onabotulinumtoxinA (onabotulinumtoxinA/onabotulinumtoxinA (O/O) and placebo/onabotulinumtoxinA (P/O) groups, respectively). HRQoL endpoints were assessed over 56 weeks using the Headache Impact Test (HIT-6) and the Migraine-Specific Quality of Life Questionnaire (MSQ). HIT-6 score reductions ≥2.3 and ≥5 denoted between-group minimally important difference and within-patient clinically meaningful response, respectively. RESULTS: A total of 1236 participants (O/O, n = 607; P/O, n = 629) participated in both phases. The DB phase showed significantly reduced HIT-6 and MSQ for onabotulinumtoxinA versus placebo (all p < 0.001). The OL phase showed significantly reduced HIT-6 for O/O versus P/O at weeks 28, 36, and 48, but not 56. All three MSQ domains showed improved HRQoL relative to baseline, but only the role restrictive domain showed a significant difference between O/O and P/O at week 56. CONCLUSIONS: Benefits of onabotulinumtoxinA on HRQoL versus baseline persisted throughout the OL phase. Statistical superiority in favor of O/O was demonstrated for HIT-6 through 48 weeks and for MSQ (role restrictive) at 56 weeks.

Direct and Indirect Costs of Chronic and Episodic Migraine in the United States: A Web-Based Survey.

OBJECTIVE: The objective of this study was to compare the societal direct and indirect costs of chronic and episodic migraine in the United States. BACKGROUND: Episodic and chronic migraine are distinguished by the frequency of headache-days. Chronic migraine has a greater overall impact on quality of life than does episodic migraine. Individuals with chronic migraine also use more healthcare resources (resulting in higher direct costs) and experience greater decreases in productivity (resulting in higher indirect costs) than those with episodic migraine as shown in the American Migraine Prevalence and Prevention (AMPP) Study. METHODS: The International Burden of Migraine Study utilized a web-based questionnaire to elicit data on several topics related to the burden of migraine illness, including health resource utilization and productivity losses. Potential survey participants were identified by Synovate Healthcare (Chicago, IL, USA) from a pool of registered panelists from various countries. The panelists were screened online to determine eligibility and to identify individuals with migraine (episodic or chronic), based on reported symptoms. Participants from the United States were divided into episodic and chronic migraine groups, based on reported headache-day per month frequency. Direct and indirect costs were estimated by applying estimated unit costs to reported headache-related productivity losses and resource use. Costs were compared between participants with episodic and chronic migraine. RESULTS: Mean [standard deviation] total annual cost of headache among people with chronic migraine ($8243 [$10,646]) was over three times that of episodic migraine ($2649 [$4634], P < .001). Participants with chronic migraine had significantly greater direct medical costs ($4943 [$6382]) and indirect (lost productivity) costs ($3300 [$6907]) than did participants with episodic migraine (direct, $1705 [$3591]; indirect, $943 [$2084]) (P < .001 for each). Unlike previous findings, direct medical costs constituted the majority of total headache-related costs for both chronic migraine (60.0%, $4943 of $8243) and episodic migraine (64.3%, $1705 of $2649) participants. A large portion of direct medical costs are attributable to pharmaceutical utilization among both chronic migraine (80%, $3925 of 4943) and episodic migraine (70%, $1196 of $1705) participants. CONCLUSION: The results of this study build on previous results of the AMPP Study, demonstrating that headache-related direct, indirect, and total costs are significantly greater among individuals with chronic migraine than with episodic migraine in the United States.

Comparative effectiveness of onabotulinumtoxinA versus oral migraine prophylactic medications on headache-related resource utilization in the management of chronic migraine: Retrospective analysis of a US-based insurance claims database.

BACKGROUND: Migraine, especially chronic migraine (CM), causes substantial disability; however, health care utilization has not been well characterized among patients receiving different migraine prophylactic treatments. METHODS: Using a large, US-based, health care claims database, headache-related health care utilization was evaluated among adults with CM treated with onabotulinumtoxinA or oral migraine prophylactic medications (OMPMs). Headache-related health care utilization was assessed at six, nine, and 12 months pre- and post-treatment. The primary endpoint was the difference between pre- and post-index headache-related health care utilization. A logistic regression model was created to test the difference between onabotulinumtoxinA and OMPM-treated groups for headache-related emergency department (ED) visits and hospitalizations. RESULTS: Baseline characteristics were comparable between groups. The proportion of patients with ED visits or hospitalizations for a headache-related event decreased after starting onabotulinumtoxinA, but increased after starting an OMPM, for all three cohorts. Regression analyses showed that the odds of having a headache-related ED visit were 21%, 20%, and 19% lower and hospitalization were 47%, 48%, and 56% lower for the onabotulinumtoxinA group compared to the OMPM group for the six-month, nine-month, and 12-month post-index periods, respectively. CONCLUSIONS: When compared with similar patients who initiated treatment with OMPM, onabotulinumtoxinA was associated with a significantly lower likelihood of headache-related ED visits and hospitalizations.

Improving the detection of chronic migraine: Development and validation of Identify Chronic Migraine (ID-CM).

BACKGROUND: Migraine, particularly chronic migraine (CM), is underdiagnosed and undertreated worldwide. Our objective was to develop and validate a self-administered tool (ID-CM) to identify migraine and CM. METHODS: ID-CM was developed in four stages. (1) Expert clinicians suggested candidate items from existing instruments and experience (Delphi Panel method). (2) Candidate items were reviewed by people with CM during cognitive debriefing interviews. (3) Items were administered to a Web panel of people with severe headache to assess psychometric properties and refine ID-CM. (4) Classification accuracy was assessed using an ICHD-3ß gold-standard clinician diagnosis. RESULTS: Stages 1 and 2 identified 20 items selected for psychometric validation in stage 3 (n = 1562). The 12 psychometrically robust items from stage 3 underwent validity testing in stage 4. A scoring algorithm applied to four symptom items (moderate/severe pain intensity, photophobia, phonophobia, nausea) accurately classified most migraine cases among 111 people (sensitivity = 83.5%, specificity = 88.5%). Augmenting this algorithm with eight items assessing headache frequency, disability, medication use, and planning disruption correctly classified most CM cases (sensitivity = 80.6%, specificity = 88.6%). DISCUSSION: ID-CM is a simple yet accurate tool that correctly classifies most individuals with migraine and CM. Further testing in other settings will also be valuable.

The negative impact of spasticity on the health-related quality of life of stroke survivors: a longitudinal cohort study.

BACKGROUND: Spasticity often leads to symptomatic and functional problems that can cause disability for stroke survivors. We studied whether spasticity has a negative impact on health-related quality of life (HRQoL). METHODS: As part of the Greater Cincinnati/Northern Kentucky Stroke Study (NCT00642213), 460 ischemic stroke patients were interviewed during hospitalization and then followed over time. HRQoL was measured by the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the Short Form-12 (SF-12), EuroQol-5 dimension (EQ-5D), and Stroke-Specific Quality of Life (SSQOL) instruments, with lower scores indicating worse health. HRQoL differences between stroke survivors with and without spasticity were compared, adjusting for age, race, stroke severity, pre-stroke function, and comorbidities. RESULTS: Of the 460 ischemic stroke patients, 328 had spasticity data available 3 months after their stroke (mean age of 66 years, 49% were female, and 26% were black). Of these patients, 54 (16%) reported having spasticity. Three months following their stroke, patients who reported spasticity had lower mean scores on the PCS (29.6 ± 1.4 vs 37.3 ± 0.6; P < .001), EQ-5D (0.59 ± 0.03 vs 0.71 ± 0.01; P < .001), and SSQOL (3.57 ± 0.08 versus 3.78 ± 0.03; P = .03) compared with patients who did not report spasticity. Lower HRQoL scores were also observed at the 1-year (PCS, EQ-5D, and SSQOL) and 2-year (EQ-5D and SSQOL) interviews in those with spasticity compared with those without spasticity. CONCLUSIONS: Statistically and clinically meaningful differences in HRQoL exist between stroke survivors with and without spasticity.

Validation of a New Patient-Reported Outcome Measure for Facial Acne: The Acne Symptom and Impact Scale (ASIS).

OBJECTIVE: The objective of this study was to evaluate the psychometric performance of the Acne Symptom and Impact Scale (ASIS) for use in adolescents and adults with acne vulgaris. METHODS: Psychometric evaluation was performed using both traditional psychometrics in line with proposed US Food and Drug Administration (FDA) criteria and new psychometric methods, Rasch Measurement Theory (RMT). Assessment of equivalence was also evaluated between Caucasians and Non-Caucasians on individual items. RESULTS: One-hundred fifty subjects completed baseline and follow-up assessments (89 [59.33%] in the Caucasian group and 61 [40.67%] in the Non-Caucasian group). Psychometric analyses demonstrated that the ASIS Sign and Impact domains both performed well. Each domain fulfilled traditional psychometric criteria (Cronbach's alpha=0.79-0.92; test-retest reliability=0.75-0.78) and mostly satisfied Rasch psychometric criteria (person-reliability=0.72-0.93; person-separation=1.61-3.69). Select individual ASIS Items also performed well across all measures and were shown to be reliable and valid as stand-alone items. A similar pattern of results were found for both Caucasian and Non-Caucasian racial subgroups. CONCLUSIONS: These findings provide empirical evidence that the ASIS is a reliable and valid PRO measure that can accurately assess the severity of symptoms and impacts associated with acne vulgaris.

Adherence to oral migraine-preventive medications among patients with chronic migraine.

BACKGROUND: Chronic migraine (CM) is a disabling disorder characterized by ≥15 headache days per month that has been shown to significantly reduce quality of life. Migraine-prevention guidelines recommend preventive medications as the standard of care for patients with frequent migraine. The aim of this study was to assess adherence to 14 commonly prescribed oral migraine-preventive medications (OMPMs) among patients with CM. METHODS: Retrospective claims analysis of a US claim database (Truven MarketScan® Databases) was queried to identify patients who were at least 18 years old, diagnosed with CM, and initiated an OMPM (antidepressants, beta blockers, or anticonvulsants) between January 1, 2008 and September 30, 2012. Medication possession ratios (MPR) and proportion of days covered (PDC) were calculated for each patient. A cutoff of ≥80% was used to classify adherence. The odds of adherence between OMPMs were compared using logistic regression models. RESULTS: Of the 75,870 patients identified with CM, 8688 met the inclusion/exclusion criteria. Adherence ranged between 26% to 29% at six months and 17% to 20% at 12 months depending on the calculation used to classify adherence (PDC and MPR, respectively). Adherence among the 14 OMPMs was similar except for amitriptyline, nortriptyline, gabapentin, and divalproex, which had significantly lower odds of adherence when compared to topiramate. CONCLUSION: Adherence to OMPMs is low among the US CM population at six months and worsens by 12 months.

Real-world economic impact of onabotulinumtoxinA in patients with chronic migraine.

OBJECTIVE: To determine whether the utilization of healthcare resources is reduced after chronic migraine patients are treated for 6 months with onabotulinumtoxinA. BACKGROUND: OnabotulinumtoxinA is indicated for headache prophylaxis in patients with chronic migraine, but its effect on healthcare resource use is unknown. METHODS: We analyzed data from an open-label study of 230 chronic migraine patients refractory to ≥2 oral prophylactics who presented to a headache specialty clinic and who were treated with two cycles of onabotulinumtoxinA. Frequency and cost of migraine-related healthcare resource use, including visits to emergency departments, urgent care, or hospitalization, were compared for the 6 months before and after initial treatment. Costs were based on publicly available sources. RESULTS: Compared with the 6 months predating initial treatment, patients had 55% fewer emergency department visits (174 vs 385), 59% fewer urgent care visits (61 vs 150), and 57% fewer hospitalizations (19 vs 45) during the 6-month treatment period (P < .01 for all). Analysis of treatment-related costs yielded an average reduction of $1219.33/patient, off-setting 49.7% of the total estimated cost for 6 months of treatment with onabotulinumtoxinA. CONCLUSIONS: Although we are unable to distinguish onabotulinumtoxinA's treatment effect from other potential confounding variables, our analysis showed that severely afflicted, treatment-refractory patients with chronic migraine experienced a significant cost-offset through reduced migraine-related emergency department visits, urgent care visits, and hospitalizations in the 6 months following treatment initiation of onabotulinumtoxinA. Future analyses will assess the longer-term effect of onabotulinumtoxinA treatment and the potential contribution of regression to the mean.

Validation of the Headache Impact Test (HIT-6) in patients with chronic migraine.

BACKGROUND: The Headache Impact Test (HIT)-6 was developed and has been validated in patients with various types of headache. The objective of this study was to report the psychometric properties of the HIT-6 among patients with chronic migraine. METHODS: Data came from two international, multicenter, randomized, double-blind, placebo-controlled clinical trials of chronic migraine patients (N = 1,384) undergoing prophylaxis therapy. Confirmatory factor analysis and differential item functioning (DIF) analysis were used to test the latent structure and cross-cultural comparability of the HIT-6. Reliability, construct validity, and responsiveness were assessed. Two sets of criterion groups were used: (1) 28-day headache frequency: <10, 10-14, and ≥15 days; (2) sample quartiles of the total cumulative hours of headache: <140, 140 to <280, 280 to <420, and ≥420 hours. Two sets of responsiveness categories were defined as reduction of <30%, 30% to <50%, or ≥50% in (1) number of headache days and (2) cumulative hours of headache. RESULTS: Measurement invariance tests supported the stability of the HIT-6 latent structure across studies. DIF analysis supported cross-cultural comparability. Good reliability was observed across studies (Cronbach's α: 0.75-0.92; intraclass correlation coefficient: 0.76-0.80). HIT-6 scores correlated strongly (-0.86 to -0.59) with scores of the Migraine-Specific Quality-of-Life Questionnaire. Analysis of variance indicated that HIT-6 scores discriminated across both types of criterion groups (P<0.001), across studies and time points. HIT-6 change scores were significantly higher in magnitude in groups experiencing greater improvement (P<0.001). CONCLUSION: All measurement properties were consistently verified across the two studies, supporting the validity of the HIT-6 among chronic migraine patients. TRIAL REGISTRATION: NCT00156910 and NCT00168428 on www.ClinicalTrials.gov.

Systematic review of migraine prophylaxis adherence and persistence.

BACKGROUND: Migraine is a common neurological disease affecting 12% of Americans and millions worldwide. Medication adherence has been studied extensively in many chronic conditions, with poor adherence adversely affecting treatment outcomes. However, little is known about adherence to oral prophylaxis for migraine. OBJECTIVE: To examine the literature on assessing oral prophylaxis medication adherence and persistence among migraine patients. METHODS: A systematic search of the PubMed (1966 to present) and EMBASE (1974 to present) databases was conducted to locate prospective and retrospective observational studies and randomized controlled trials (RCTs) of propranolol, amitriptyline, and topiramate. RCTs were pooled, weighted by sample size, and stratified by drug and length of study. Average persistence rates and reasons for discontinuation cited in RCTs were examined for each medication. RESULTS: A total of 788 unique articles were identified using the search criteria, 33 of which were included in the final review. Observational studies (n = 14) showed adherence ranges of 41% to 95% at 2 months, 21% to 80% at 6 months, and 35% to 56% at 12 months and persistence ranges of 41% to 88% at 2 months, 19% to 79% at 6 months, and 7% to 55% at 12 months. Pooled persistence from RCTs on propranolol, amitriptyline, and topiramate (n = 19) showed rates of 77%, 55%, and 57%, respectively, at 16-26 weeks. Adverse events were the most common reason for discontinuation cited (24% for topiramate and 17% for amitriptyline). CONCLUSION: Observational studies and pooled data from RCTs demonstrate poor adherence and persistence to oral migraine prophylaxis.

Headache-related health resource utilisation in chronic and episodic migraine across six countries.

OBJECTIVE: To describe headache-related health resource usage in chronic and episodic migraine across six countries. METHODS: A web-based questionnaire eliciting data on several topics, including health resource usage, was administered to panellists with migraine from the USA, Canada, UK, Germany, France and Australia. Respondents were grouped into episodic and chronic migraine, based on reported headache phenotype and headache-day frequency. ORs were calculated, comparing usage in each country to that in the US, controlling for chronic versus episodic migraine and other factors. RESULTS: Relative to the USA, the odds of visiting a provider for headache during the preceding 3 months were significantly higher in all countries, except Germany. Respondents in France were more likely to report having a provider they typically visited for headache-related care. The odds of visiting the emergency department for headache were significantly lower in France, the UK and Germany, and hospitalisation for headache was significantly more frequent in Canada and Australia. Respondents from all countries, except Canada, were more likely to report currently using a prescription-acute treatment, and those from France were more likely to report trying more than three acute treatments. Preventive treatment use did not differ significantly. CONCLUSIONS: Headache-related resource usage differed significantly between the USA and other countries. US respondents were generally less likely to report recent provider visits and use of prescription-acute treatments. They were more likely to report emergency department visits than in European countries, but less likely to report hospitalisation than in Canada and Australia.

The cost-effectiveness of onabotulinumtoxinA for the prophylaxis of headache in adults with chronic migraine in the UK.

BACKGROUND: Although chronic migraine is associated with substantial disability and costs, few treatments have been shown to be effective. OnabotulinumtoxinA (Botox, Allergan Inc., Irvine, CA) is the first treatment to be licensed in the UK for the prophylaxis of headaches in adults with chronic migraine. This study aims to evaluate the cost-effectiveness of onabotulinumtoxinA in this indication in the UK. METHODS: A state-transition (Markov) model was developed comparing onabotulinumtoxinA to placebo. Efficacy data and utility values were taken from the pooled Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trials program (n = 1384). Estimates of resource utilisation were taken from the International Burden of Migraine Study (IBMS), and stopping rules were informed by published medical guidelines and clinical data. This study estimated 2-year discounted costs and quality-adjusted life years (QALYs) from the UK National Health Service perspective. RESULTS: At 2 years, treatment with onabotulinumtoxinA was associated with an increase in costs of £1367 and an increase in QALYs of 0.1 compared to placebo, resulting in an incremental cost-effectiveness ratio (ICER) of £15,028. Treatment with onabotulinumtoxinA reduced headache days by an estimated 38 days per year at a cost of £18 per headache day avoided. Sensitivity analysis showed that utility values had the greatest influence on model results. The ICER remained cost-effective at a willingness to pay threshold of £20,000-£30,000/QALY in the majority of scenario analyses as well as in probabilistic sensitivity analysis, where onabotulinumtoxinA was cost-effective on 96% of occasions at a threshold of £20,000/QALY and 98% of occasions at £30,000/QALY. CONCLUSION: OnabotulinumtoxinA has been shown to reduce the frequency of headaches in patients with chronic migraine and can be considered a cost-effective use of resources in the UK National Health Service. The uncertainties in the model relate to the extrapolation of clinical data beyond the 56-week trial.

Adherence associated with oral medications in the treatment of spasticity.

OBJECTIVE: To examine adherence to baclofen, tizanidine, and dantrolene (U.S. Food and Drug Administration-approved oral spasticity medications), and identified determinants of adherence. DESIGN: A retrospective administrative claims data analysis that used medical and pharmacy claims data and enrollment information from a large, national U.S. health plan. SUBJECTS AND METHODS: The subjects were commercial health plan members who initiated treatment on baclofen, tizanidine, or dantrolene from January 1, 2004, through September 30, 2009, and who had stroke, spinal cord injury, traumatic brain injury, cerebral palsy, or multiple sclerosis. Descriptive and logistic regression statistical analyses were performed. MAIN OUTCOME MEASUREMENTS: Outcomes were adherence, measured as continuous medication possession ratio (MPR) and as a binary indicator (MPR ≥0.80, adherent; MPR <0.80, nonadherent), change in oral spasticity medication, and use of nonoral spasticity therapy. RESULTS: The study population included 2840 subjects. Adherence overall was poor: the range of mean unadjusted MPR values was 0.10-0.50, which indicated that, at best, the subjects were adherent to their index spasticity medications for 50% of their treatment periods. Unadjusted overall MPRs for baclofen and tizanidine were 20.4% and 9.1%, respectively. Fewer than 5% of subjects changed oral spasticity medications. The results of logistic regression to identify determinants of adherence showed that subjects treated with tizanidine versus baclofen had 37.4% lower odds of adherence and that subjects with traumatic brain injury versus stroke had 77.5% lower odds of adherence. The odds of adherence increased with age and with preindex contracture or decubitus ulcer. CONCLUSIONS: Adherence to oral spasticity medication was poor irrespective of index spasticity medication or condition. Results from this study indicated that physicians cannot assume that patients are adherent to prescribed oral spasticity medications. A more complete understanding of the reasons behind nonadherence is required.

Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second international burden of migraine study (IBMS-II).

OBJECTIVE: Our objective was to characterize patterns of preventive medication use in persons with episodic migraine (EM) and chronic migraine (CM). BACKGROUND: Several classes of medications are used both on- and off-label for the prevention of migraine, including ß-blockers (eg, propranolol, timolol), tricyclic antidepressants (eg, amitriptyline), anti-epileptic drugs (eg, topiramate, valproic acid), and neurotoxins (eg, onabotulinumtoxinA). METHODS: Preventive medication use and reasons for discontinuation were collected in an international, Web-based, cross-sectional survey of adults with migraine during 2010. Descriptive analyses were conducted on demographics and headache-related disability as measured by the Migraine Disability Assessment Scale, stratified by use of preventive medication, and EM or CM. Univariate and multivariate logistic regression models were constructed to assess predictors of preventive medication use. RESULTS: One thousand one hundred and sixty-five respondents completed the survey. Only 28.3% of EM and 44.8% of CM respondents were currently using preventive medication; any use of prophylaxis (prior or current) was reported by 43.4% of those with EM and 65.9% with CM. The mean number of prophylactic medications ever used was 2.92 for EM and 3.94 for CM. Antidepressants were used most frequently (EM 60.9%; CM 54.7%), followed by ß-blockers (EM 35.4%; CM 36.8%) and anti-epileptics (EM 28.6%; CM 36.3%). Odds of preventive medication use were higher among CM than EM, adjusting for age, gender, race, years of daily headache, and country (odds ratio 2.72; 95% confidence interval 2.15 to 3.57). Greater headache-related disability and older age were also associated with greater odds of ever having used prophylaxis, regardless of headache frequency. CONCLUSIONS: Less than half the persons with EM and CM were currently using preventive medication for migraine, with treatment rates being higher for CM, as expected. Those with CM tried more medications than those with EM, possibly reflecting higher levels of treatment need.

Cost and predictors of lost productive time in chronic migraine and episodic migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study.

OBJECTIVE: To quantify the cost differences and predictors of lost productive time (LPT) in persons with chronic migraine (CM) and episodic migraine (EM). METHODS: The American Migraine Prevalence and Prevention (AMPP) study is a US national longitudinal survey of severe headache. Cost estimates were obtained via U.S. Census income data. To elucidate the unique predictors of LPT, the optimal distribution for modeling was determined. Zero inflation models for LPT were predicted from sociodemographics, headache features, characteristics and disability, medication use, and depression. The interaction between headache status and age was the primary effect of interest. RESULTS: The eligible sample included 6329 persons with EM and 374 persons with CM. Men with CM aged 45 to 54 years cost employers nearly $200 per week more than do their EM counterparts. Likewise, for women, costs were higher for CM, with the cost differential between EM and CM being $90 per week. After comprehensive adjustment, increases in LPT with age were significantly higher in CM than in EM (rate ratio 1.03; 95% confidence interval 1.01-1.05). When age was recoded to a decade, metric rates of LPT increased 25% more per decade for CM than for EM (rate ratio 1.25; 95% confidence interval 1.004-1.5). CONCLUSIONS: LPT is more costly and increases more rapidly for those with CM than for those with EM as age increases.

The psychometric properties of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) in chronic migraine patients.

OBJECTIVE: The Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) has been shown to have good psychometric performance in measuring headache impact in migraine patients, but its properties specifically in chronic migraine (CM) patients are unknown. The objective of this study was to evaluate the psychometric properties of the MSQ in a group of CM patients undergoing prophylactic treatment. METHODS: Measurement properties of the MSQ were examined using two international, multicenter, randomized clinical trials evaluating onabotulinumtoxinA as headache prophylaxis in CM patients (N = 1,376). Confirmatory factor analysis (CFA) was used to test the latent structure of the MSQ in CM patients. The reliability, convergent and discriminant validity, and responsiveness of the MSQ were assessed. RESULTS: CFA confirmed the currently proposed three-factor MSQ latent structure across the two studies. Good reliability was observed for all three MSQ scales, across studies and time points. MSQ scale scores strongly correlated with the scores of the Headache Impact Test-6 (HIT-6). Analysis of known-groups validity indicated that MSQ scale scores discriminated between groups of patients differing in their 28-day headache frequency were as follows <10, 10-14, and ≥ 15 days, and the sample-derived quartiles of the total cumulative hours of headache were as follows <140, 140 to <280, 280 to <420, and ≥ 420 h (p < 0.0001), across both studies and time points. MSQ change scores were higher in magnitude in groups experiencing greater decline in headache frequency (p < 0.001). CONCLUSION: The MSQ is a psychometrically valid tool that can be used to reliably measure the impact of migraine among CM patients.

Mapping from disease-specific measures to health-state utility values in individuals with migraine.

OBJECTIVE: The objective of this study was to develop empirical algorithms that estimate health-state utility values from disease-specific quality-of-life scores in individuals with migraine. METHODS: Data from a cross-sectional, multicountry study were used. Individuals with episodic and chronic migraine were randomly assigned to training or validation samples. Spearman's correlation coefficients between paired EuroQol five-dimensional (EQ-5D) questionnaire utility values and both Headache Impact Test (HIT-6) scores and Migraine-Specific Quality-of-Life Questionnaire version 2.1 (MSQ) domain scores (role restrictive, role preventive, and emotional function) were examined. Regression models were constructed to estimate EQ-5D questionnaire utility values from the HIT-6 score or the MSQ domain scores. Preferred algorithms were confirmed in the validation samples. RESULTS: In episodic migraine, the preferred HIT-6 and MSQ algorithms explained 22% and 25% of the variance (R(2)) in the training samples, respectively, and had similar prediction errors (root mean square errors of 0.30). In chronic migraine, the preferred HIT-6 and MSQ algorithms explained 36% and 45% of the variance in the training samples, respectively, and had similar prediction errors (root mean square errors 0.31 and 0.29). In episodic and chronic migraine, no statistically significant differences were observed between the mean observed and the mean estimated EQ-5D questionnaire utility values for the preferred HIT-6 and MSQ algorithms in the validation samples. CONCLUSIONS: The relationship between the EQ-5D questionnaire and the HIT-6 or the MSQ is adequate to use regression equations to estimate EQ-5D questionnaire utility values. The preferred HIT-6 and MSQ algorithms will be useful in estimating health-state utilities in migraine trials in which no preference-based measure is present.