Understanding treatment goals and their application in clinical trial design for patients with Alzheimer disease and caregivers.

Background: As research continues towards improved treatments for Alzheimer disease (AD), there is growing interest in the views and needs from patients and caregivers on AD treatments. Methods: In this study, we surveyed patients with AD and caregivers to determine the treatment goals that are most important to them. Patients with AD and caregivers were independently recruited in Europe and North America to complete a web-based survey. Eligible participants were ≥18 years old and diagnosed with mild cognitive impairment or mild-to-moderate AD (patient-reported group) or persons involved in the care of patients with AD (caregiver-reported group). A total of 322 patients and 614 caregivers completed the survey. Results: The demographic characteristics of patients in the patient-reported and the caregiver-reported groups were similar. Disease severity of patients was greater in the caregiver-reported group compared with the patient-reported group (72.1% versus 46.9% moderate AD). The most important goal of AD treatment in both groups was maintenance of quality of life (QoL) (patient-reported group 31.1% and caregiver-reported group 38.8%; p=0.01). This was consistent across disease stages or symptom severity except for patients with mild cognitive impairment in the caregiver-reported group where slowing the progression of memory loss was the most important treatment goal. Conclusions: Patient QoL was consistently the most relevant treatment goal for patients with AD and caregivers. In AD clinical trials, patient-relevant outcomes, for example, QoL, should be given high priority to reflect the needs and demands of patients with AD and their caregivers.A preliminary report of this work was presented at the 14th Clinical Trials on Alzheimer's Disease meeting (November 9-12, 2021).

Application of a Novel Endpoint Staging Framework: Proof of Concept in the AMBAR Study.

Background: A theoretical endpoint staging framework was previously developed and published, aligning outcomes (i.e., memory) to the stage of Alzheimer's disease (AD) in which a given outcome is most relevant (i.e., has the greatest risk of degradation). The framework guides the selection of endpoints measuring outcomes relevant within a target AD population. Here, a proof of concept is presented via post-hoc analyses of the Alzheimer Management by Albumin Replacement (AMBAR) Phase 2b clinical trial in patients with AD (NCT01561053, 2012). Objective: To evaluate whether aligning endpoints measuring cognition, function, and quality of life to hypothesized 'target' stages of AD yields magnitudes of treatment efficacy greater than those reported in the AMBAR full analysis set (FAS). Methods: Three endpoints were tested: ADAS-Cog 12, ADCS-ADL, and QoL-AD. The magnitude of treatment efficacy was hypothesized to be maximized in the target stages of mild, mild-to-moderate, and very mild AD, respectively, compared to the full analysis set (FAS) and non-target stages. Results: For ADAS-Cog 12, the magnitude of treatment efficacy was largest in the non-target stage (-4.0, p = 0.0760) compared to target stage and FAS. For ADCS-ADL and QoL-AD, the magnitude of treatment efficacy was largest in the target stage (14.2, p = 0.0003; 2.4, p < 0.0001, respectively) compared to non-target stage and FAS. Conclusions: Findings indicated that evaluating endpoints in the most relevant AD stage can increase the magnitude of the observed treatment efficacy. Evidence provides preliminary proof of concept for the endpoint staging framework.

Toward the optimized assessment of clinical outcomes in studies of novel treatments for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is characterized by a progressive decline in cognition and daily function, leading to a greater need for caregiver support. Clinical disease is segmented into a preclinical stage, mild cognitive impairment, and mild, moderate, and severe stages of Alzheimer's dementia. Although AD trials enroll participants at various stages of illness, treatment efficacy is often assessed using endpoints based on measures of outcomes that are held fixed across disease stages. We hypothesize that matching the primary outcomes measured in the endpoint hierarchy to the stage of disease targeted by the trial will increase the likelihood of detecting true treatment benefits. AREAS COVERED: We discuss current approaches to assessing clinical outcomes in AD trials, followed by a consideration of how effect detection can be improved by linking the stage of AD to the endpoints that most likely reflect stage-specific disease progression. EXPERT OPINION: Failing to account for stage-specific relevance and sensitivity of clinical outcomes may be one factor that contributes to trial failures in AD. Given the history of failure, experts have begun to scrutinize the relevance and sensitivity of outcomes as a potentially modifiable barrier to successful trials. To this end, we present a framework for refining trial endpoint selection and evaluation.

Comorbidity Associations with AATD Among Commercially Insured and Medicare Beneficiaries with COPD in the US.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is often not identified in patients with chronic obstructive pulmonary disease (COPD) until advanced stages of disease, despite the availability of genetic testing. While clinical practice guidelines provide recommendations on patients who should be tested, more refined algorithms are needed to identify COPD patients who are likely candidates for AATD testing and to prevent delays in diagnosis and treatment. The objective of this study was to identify comorbid associations with AATD among patients diagnosed with COPD in the United States. Methods: Using data from the 2012-2017 PharMetrics Plus Administrative Claims Database and 2011-2014 Medicare Fee for Service 5% Sample, patients with COPD (ICD-9-CM: 491.xx, 492.xx, or 496, ICD-10-CM J41, J42, J43, J44) and AATD (ICD-9-CM: 273.4, ICD-10-CM: E88.01) were identified. Patient demographic and diagnostic characteristics were assessed. Logistic regression models were developed to identify significant predictors of AATD. Results: A cohort of 344,528 Medicare beneficiaries with COPD (of which 302 (0.09%) also had two diagnoses of AATD) and a cohort of 340,259 commercially insured patients with COPD (of which 1076 (0.3%) also had a diagnosis of AATD) were constructed. Associations with AATD identified in both models included ICD-9-CM and ICD-10-CM codes for chronic pulmonary heart disease, chronic liver disease and cirrhosis, and liver transplant. Discussion: Significant associations with a diagnosis of AATD among patients with COPD were consistently represented in each of the datasets evaluated, which suggests meaningful comorbidity implications in AATD patients. These findings reinforce the need to test individuals with COPD for AATD as early as possible to help reduce the development of associated comorbid conditions.

Correction to: The cost-effectiveness of albumin in the treatment of decompensated cirrhosis in Germany, Italy, and Spain.

Following publication of the original article [1], the authors reported that one of the numbers within Fig. 6 contains a mistake.

Immunoglobulin administration for the treatment of CIDP: IVIG or SCIG?

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired neurological disorder characterized clinically by weakness and impaired sensory function evolving over 2 months or more, loss or significant decrease in deep tendon reflexes, and by electrophysiological evidence of peripheral nerve demyelination. Expeditious diagnosis and treatment of CIDP early in the disease course is critical such that irreversible disability can be avoided. Intravenous immunoglobulin (IVIG) is one first-line and maintenance therapy option for CIDP. The US Food & Drug Administration's (FDA's) approval of subcutaneous immunoglobulin (SCIG) in 2018 provides patients with CIDP more treatment options for maintenance therapy. The different options for administration of IG treatment create the need for information to assist clinicians and patients in choosing the optimal therapeutic approach. Considerations for pharmacokinetics, administration procedures, adverse events, patient variables, and cost will all be discussed in this article.

The cost-effectiveness of albumin in the treatment of decompensated cirrhosis in Germany, Italy, and Spain.

BACKGROUND: Albumin is frequently prescribed in cirrhotic patients with acute decompensation. However, the true cost effectiveness of albumin use in cirrhotic patients is still under debate. OBJECTIVE: To evaluate the cost-effectiveness of albumin in the treatment of decompensated cirrhosis in Germany, Italy, and Spain. METHODS: A decision-tree economic model was developed to evaluate treatments for decompensated cirrhosis from the hospital perspective over a typical inpatient admission. The treatments for large volume paracentesis (LVP) were albumin vs saline, gelatin, or no fluid. The treatments for spontaneous bacterial peritonitis (SBP) were albumin plus antibiotics vs antibiotics alone. The treatments for hepatorenal syndrome (HRS) were albumin plus a vasoconstrictor vs a vasoconstrictor alone. Effectiveness inputs were literature-based. Cost inputs included pharmacy costs and medical complication costs of decompensated cirrhosis. The primary model assessments were incremental cost-effectiveness ratios (ICERs) per life saved and per quality-adjusted life-year (QALY). RESULTS: Albumin was found to be both less costly and more effective relative to saline, gelatin, and no fluid for the treatment of LVP across all 3 countries. For SBP, albumin plus antibiotics was more clinically effective than antibiotics alone in all 3 countries. The combination of albumin plus antibiotics was less costly than antibiotics alone in Germany and Italy, making albumin a dominant treatment (ie, less costly and more effective). In the management of SBP in Spain, albumin plus antibiotics compared to antibiotics alone resulted in ICERs of €1516 per life saved and €3369 per QALY gained. Albumin plus a vasoconstrictor was both less costly and more effective than vasoconstrictor alone in the treatment of HRS across all 3 countries. CONCLUSION: This analysis demonstrates that albumin is cost-effective in terms of lives saved and QALYs gained in the management of decompensated cirrhosis associated with LVP, SBP, or HRS.

Treatment Patterns and Costs of Chronic Inflammatory Demyelinating Polyneuropathy: A Claims Database Analysis.

BACKGROUND: Corticosteroids, plasma exchange, and intravenous immunoglobulin (IVIG) have been standard-of-care treatments for chronic inflammatory demyelinating polyneuropathy (CIDP) for more than 2 decades. Despite guideline recommendations for best clinical practices, heterogeneity in patient presentation and the course of treatment for CIDP remains. There is limited literature regarding the real-world treatment patterns of and costs associated with CIDP. OBJECTIVE: To analyze and describe the real-world treatment patterns of and economic burden associated with CIDP. METHODS: This retrospective cohort study evaluated the treatment patterns and CIDP-related healthcare costs over a 2-year follow-up period for patients with newly diagnosed CIDP who had commercial insurance, using claims data from the IMS LifeLink PharMetrics Plus Claims database between 2009 through 2014. Treatment-naïve patients with newly diagnosed CIDP were evaluated for 2 years postdiagnosis, which captured the treatments used and the resource utilization. The patients were defined as receiving active CIDP therapy (ie, IVIG, immunosuppressants, oral or intravenous steroids, or plasma exchange) or active surveillance. RESULTS: Of the 525 patients identified with newly diagnosed CIDP, 55.2% of patients were prescribed only steroid therapy, and 25.3% of patients were prescribed an IVIG therapy during the 2-year follow-up. The median time to the initial treatment was shortest for patients receiving plasma exchange alone (0.03 months) or in combination with a steroid (0.03 months), followed by IVIG plus another therapy (0.53 months), and then IVIG alone (0.71 months). Initiating therapy with steroids alone took the longest mean time (6.51 months) to start the treatment. The median length of time to receive therapy was longest for the steroid plus plasma exchange cohort (21.8 months), followed by the steroid plus immunosuppressant cohort (10.1 months), and the 2 IVIG cohorts (9.04 months for IVIG alone and 9.82 months for IVIG plus another therapy). The mean total CIDP-specific 2-year follow-up costs were highest for the cohort that received IVIG alone ($119,928) or with an additional therapy ($133,334) and lowest for patients who received active surveillance ($3723) or steroids alone ($3101). CONCLUSIONS: Steroid therapy was initiated later and resulted in a shorter duration of treatment than other treatment options for patients with CIDP, which may reflect diagnostic uncertainty, disease severity or remission, therapeutic challenge to determine diagnosis, or the side-effect profile of steroids. The use of steroids alone was the most common prescribed treatment for CIDP. Further research is needed to understand the rationale for treatment decisions in this patient population and their potential impact on patients and health plans.

Two comparative assessments of intravenous immunoglobulin therapy switching patterns in the treatment of chronic inflammatory demyelinating polyneuropathy in the US.

Purpose: For chronic inflammatory demyelinating polyneuropathy (CIDP) patients, each branded intravenous immunoglobulin (IVIG) treatment differs in production processes, virus elimination, formulation, and composition. Given the limited availability of real-world data comparing IVIGs for CIDP, this study evaluated switching patterns between IVIG products in 2 separate retrospective databases. Patients and methods: Two independent analytic teams retrospectively evaluated IVIG treatment-naïve patients with an ICD diagnosis code for CIDP. Study 1 used integrated healthcare claims from IMS LifeLink PharMetrics Plus™ and Study 2 used the Truven MarketScan® Database. All analyses were descriptive, with outcomes assessed during the 2-year post-index period. Results: One-quarter of IVIG patients switched therapies within the 2-year study period. In both studies, switching rates were lowest for IVIG-G (Gamunex®-C) (Study 1: 9.8%, Study 2: 8.9%), followed by IVIG-F (Flebogamma®) (Study 1: 25.0%, Study 2: 18.2%), and highest for IVIG-other (Octagam®/Gammaplex®) (Study 1: 50.0%, Study 2: 33.3%). When patients were switched, most switched to IVIG-G (Study 1: 51.6%, Study 2: 54.3%). Conclusion: The small proportion of CIDP switchers in 2 independent studies suggests that IVIG therapy is generally well tolerated. However, differences existed in switch rates for different IVIG products. The reason for low switching rates could not be assessed in this study; therefore, further studies are required to detect possible relevant differences in effectiveness and tolerability.

Cost analysis of plasma-derived factor VIII/von Willebrand factor versus recombinant factor VIII for treatment of previously untreated patients with severe hemophilia A in the United States.

BACKGROUND: Inhibitor development to factor VIII (FVIII) hemophilia therapy results in increased complications and substantial economic costs. The SIPPET study, the first randomized controlled trial to compare the immunogenicity of plasma-derived FVIII (pdFVIII)/von Willebrand factor (VWF) and recombinant-DNA-derived FVIII (rFVIII), demonstrated higher inhibitor rates in previously untreated patients (PUPs) treated with rFVIII than in PUPs treated with pdFVIII/VWF. OBJECTIVE: To quantify the economic impact of treating PUPs with pdFVIII/VWF vs rFVIII. METHODS: An Excel-based clinical and economic model was developed from a US healthcare payer perspective and run over a 5-year period. The analysis utilized a cohort approach to model patient treatment and outcomes over a monthly cycle to quantify differences in costs of FVIII, bypassing agents, and hospitalizations for serious bleeds. Rates of high-titer inhibitor development were obtained from the SIPPET study. Patients developing high-titer inhibitors were treated with immune tolerance induction (ITI). Patients who developed low-titer inhibitors and those who did not develop inhibitors continued their usual FVIII treatment. Patients who were successfully treated with ITI returned to FVIII treatment, while unsuccessfully treated patients received bypassing agents. Total costs per treated patient were estimated and a one-way sensitivity analysis was conducted to quantify the impact of parameter uncertainty on the model outcomes. RESULTS: Total cumulative costs per patient over 5 years were $834,621 for pdFVIII/VWF patients and $1,237,163 for rFVIII patients, representing a total saving of $402,542 per patient over the 5-year period, for an average annual saving of $80,508 per patient. CONCLUSIONS: Based on data from the SIPPET study, this analysis found that initiating FVIII treatment in severe hemophilia A PUPs with pdFVIII/VWF has the potential to offer substantial cost savings to healthcare payers, amounting to a one-third reduction in costs.

The dilemma of diabetes in chronic inflammatory demyelinating polyneuropathy.

PURPOSE: We reviewed the literature on chronic inflammatory demyelinating polyneuropathy (CIDP) in diabetes mellitus (DM) and explored real-world data on the prevalence and treatment of CIDP within DM. METHODS: A literature search of Scopus was performed for the terms chronic inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyneuropathy, CIDP, and prevalence, incidence, epidemiology, or diabetes; peripheral neuropathy and prevalence or diabetes. We also searched through the reference lists of the resulting publications for additional findings that may have been missed. Additional publications on guidelines for the diagnosis of CIDP and diabetic neuropathy were also included. A descriptive analysis of the 2009-2013 PharMetrics Plus™ Database was performed to estimate the prevalence and treatment of CIDP within the DM population. RESULTS: There is an increasing body of literature suggesting that the prevalence of CIDP tends to be higher in diabetic patients, especially in those of older age. Our real-world data seem to support published findings from the literature. For the total cohort (N=101,321,694), the percent prevalence of CIDP (n=8,173) was 0.008%; DM (n=4,026,740) was 4%. The percent prevalence of CIDP without DM (n=5,986) was 0.006%; CIDP with DM (n=2,187) was 9-fold higher at 0.054%. For patients >50years old, there was a significantly higher percentage of CIDP with DM than CIDP without DM. Approximately 50% of CIDP patients were treated with IVIg, 23%-24% with steroids, 1%-2% with PE, and 20%-23% received no treatment. CONCLUSIONS: In addition to the growing evidence of higher prevalence of CIDP in DM, our findings reinforce the need for heightened awareness of the association of CIDP and DM.

Migraine-related healthcare resource use and costs for subjects prescribed fixed-dose combination sumatriptan/naproxen sodium vs. single-entity oral triptans in a managed care population in the USA.

BACKGROUND: Randomized clinical trials have demonstrated that the efficacy of a fixed-dose single-tablet combination containing sumatriptan and naproxen sodium (S/NS) was greater than either of its individual components. Simplifying drug regimens (e.g., via a fixed-dose combination) has been shown to improve "real-world" outcomes by reducing pill burden and treatment regimen complexity, improving adherence, and reducing healthcare resource use and associated costs; however, no studies assessing such outcomes have been conducted to date for the acute treatment of migraine. OBJECTIVE: To assess migraine-related healthcare resource use and associated costs for subjects prescribed S/NS vs. subjects prescribed single-entity oral triptans (SOTs) within a managed care population in the USA. METHODS: In this retrospective analysis of administrative claims data from July 1, 2008 to December 31, 2009 (IMS LifeLink), subjects meeting the following criteria were selected: one or more pharmacy claim(s) for either S/NS or SOT (index date), aged 18-64 years; at least one migraine diagnosis, and continuous enrollment in the 6 months prior to and post the index date. The study population was subsequently stratified for two analyses: triptan-naïve (triptan naïve in the 6-month period prior to the index date) and triptan-switch (triptan user in the 6-month period prior to the index date and switching to another triptan). Subjects prescribed S/NS were propensity-score matched with subjects prescribed SOT (triptan-naïve analysis: 1:3; triptan-switch analysis: 1:1) to assess differences in healthcare resource use and associated costs (2009 US$) between the S/NS and SOT groups. RESULTS: Results from the triptan-naïve and triptan-switch analyses suggest that subjects prescribed S/NS are likely to have similar healthcare resource use patterns as those either newly initiated on an SOT or switching SOTs, as measured by migraine medication use, migraine-related healthcare resource use, and all-cause healthcare resource use. One exception was the observed increased use of opioids in the SOT group compared with the S/NS group (change in mean number of tablets pre-index vs. post-index, S/NS vs. SOT; triptan-naïve analysis: 8.6 vs.18.3, p = 0.045; triptan-switch analysis: -8.2 vs. 17.7; p = 0.120). Total costs from the triptan-naïve analysis indicated that the S/NS group had lower migraine-related (US$744 vs. US$820; p = 0.067) and all-cause healthcare costs (US$4,391 vs. US$4,870; p = 0.040) when compared with the SOT group, driven by savings in medical costs (migraine-related: US$252 vs. US$380; p = 0.001; all-cause: US$3,023 vs. US$3,599; p = 0.014). However, no significant differences were observed for total costs from the triptan-switch analysis (migraine-related healthcare costs, S/NS vs. SOT: US$1,159 vs. US$1,117; p = 0.929; all-cause healthcare costs: US$5,128 vs. US$4,788; p = 0.381). CONCLUSION: Study results suggest similar healthcare resource use patterns and associated costs when comparing S/NS and SOT across a triptan-naïve and triptan-experienced population. While the current study focuses on direct medical costs, future studies should extend beyond such a perspective to explore functional status, productivity, and health-related quality of life and satisfaction, attributes not captured in administrative claims data, but nonetheless important treatment goals.

Consistency of return to normal function, productivity, and satisfaction following migraine attacks treated with sumatriptan/naproxen sodium combination.

OBJECTIVES: To assess the consistency of improved functioning, productivity, and medication satisfaction in migraines treated with a single tablet of sumatriptan 85 mg/naproxen sodium 500 mg (S/NS) using an early intervention approach. METHODS: Two randomized, double-blind, placebo-controlled, 4-period crossover, multi-attack, multi-center, outpatient studies of moderate to severe adult migraineurs were conducted to compare S/NS with placebo. Participants recorded outcome assessments in a diary during the 24 hours following study medication. Analyses were conducted on the intent-to-treat population who treated at least 1 attack. Statistical significance between treatment groups used analysis of variance repeated measures models and the intent-to-treat population. There were no corrections for multiplicity. RESULTS: Almost half (48.5%) of migraineurs treated with S/NS returned to normal functioning at 2 hours and 73.3% at 4 hours postdose, compared with 28.7% (2 hours) and 43.3% (4 hours) of placebo-treated attacks. Total productivity loss over the 24 hours postdose was significantly reduced following S/NS treatment (2.5 hours on average) compared with placebo (4.0 hours). Sumatriptan/naproxen treatment resulted in significantly higher medication satisfaction scores on the efficacy, functionality, and total efficacy subscales compared with placebo in all attacks in both studies. Sumatriptan/naproxen treatment also provided significantly greater ease of use in 7 of the 8 attacks. Although tolerability was high in both treatment groups (over 90%), the placebo group was significantly less bothered by side effects in 6 of 8 attacks. CONCLUSION: Results from these 2 randomized, double-blind, placebo-controlled, multi-attack, crossover studies demonstrated the rapid and consistent restoration of patients' functioning, the consistent reduction in productivity loss, and high satisfaction ratings from patients treating multiple migraine attacks with S/NS using an early intervention approach.

Impact of NSAID and Triptan use on developing chronic migraine: results from the American Migraine Prevalence and Prevention (AMPP) study.

OBJECTIVES: To assess the influence of triptan or nonsteroidal anti-inflammatory drug (NSAID) use on the likelihood of developing chronic migraine (CM) among persons with episodic migraine (EM). BACKGROUND: CM is common in tertiary headache care, and relative to EM, CM is associated with a number of deleterious outcomes, including higher headache-related disability, reduced health-related quality of life, and increased direct and indirect costs. Symptomatic medication use has emerged as an important risk factor for the development of CM. Limited evidence based on a single year of follow up suggests that the association between NSAID and triptan use with the onset of CM varies in a dose-dependent manner that interacts with headache frequency. However, this interaction has never been explicitly studied. Herein, we evaluate results from a large-scale, 5-year, population-based observational study to characterize these relationships and test the hypothesis that NSAID use may modify the effect of triptan use on CM onset. METHODS: In the American Migraine Prevalence and Prevention (AMPP) study, 11,249 participants had EM in 2005 and provided up to 5 years of annual follow-up data. We analyzed the characteristics of persons with EM 1 year that predicted new onset CM in the subsequent year, focusing on treatment with NSAIDs and triptans as exposures. These adjacent years of data provide the basis for analysis and are termed "couplets." Repeated measures logistic regression with a subject-specific random intercept was used to model the likelihood of transition from EM to CM as a function of NSAID or triptan dose while controlling for a number of covariates including headache features, use of other medications, and the number of couplets per individual. RESULTS: The analysis included 9031 individuals with EM contributing up to 5 years of data and up to 4 couplets each. Results indicated that on average, 55% of the participants used NSAIDs in any given year and 2% transitioned to CM over subsequent years. Among the 20% using triptans, 3% per year transitioned to CM. Among persons with less than 10 headache days per month, frequency of NSAID use was associated with dose-dependent reductions in risk of CM onset. Among those with 10-14 headache days per month, increasing days per month of NSAID use was associated with increasing risk of CM onset. Increasing days per month of triptan use was associated with increased risk of transitioning to CM. Combination use of NSAIDs and triptans was not protective against transition to CM, but was also not statistically significantly associated with increased risk of CM onset. CONCLUSION: Triptan use in EM is associated with an increased risk of CM onset that increases with days of medication use. For NSAIDs, effects depend on headache days per month. NSAIDs are protective in individuals with less than 10 headache days per month but associated with increased risk with 10 or more headache days per month. Combining a triptan and NSAID was not associated with a statistically significant increased risk of CM onset, whereas increased risk of CM onset was significantly associated with triptan monotherapy.

A cross-sectional survey to assess the migraineur's medication decision-making beliefs: determining when a migraine is triptan-worthy.

OBJECTIVES: To investigate the factors that influence a migraineur's beliefs regarding oral triptans for the acute treatment of migraines and to provide further insight into patients' decision-making process when faced with migraine. METHODS: A multicenter, cross-sectional, observational study of subjects currently prescribed an oral triptan medication for the acute treatment of migraine headaches. Subjects were recruited from 6 headache clinics and one primary care practice in the United States. Enrolled subjects completed a questionnaire that could be completed either at the site as part of the visit or at home. The questionnaire comprised 27 questions assessing demographic characteristics, migraine history, migraine frequency and severity, and general beliefs about migraine treatments. The study population was stratified into 2 cohorts (Early Treatment and Delayed Treatment) based on how they typically use their oral triptan to treat a typical migraine. RESULTS: A total 506 subjects were enrolled in the study, of which 502 were stratified into the Early Treatment cohort (41.2%) and Delayed Treatment cohort (58.8%). Demographic and clinical characteristics were generally similar between the 2 cohorts. In terms of general treatment patterns, there were notable differences between the Delayed and Early Treatment cohorts, with the Delayed Treatment cohort significantly more likely to take an over-the-counter (OTC) or non-triptan medication first (P ≤ .001) and only take a triptan if the OTC or non-triptan medication did not work (P ≤ .001). Furthermore, 55% of the Delayed Treatment cohort delayed taking a triptan to be certain that the headache was a migraine (vs 32% of the Early Treatment cohort; P ≤ .001). When asked to specify the reasons for delaying treatment with a triptan, the Delayed Treatment cohort had, in general, greater concerns about using their oral triptan in comparison with the Early Treatment cohort. In particular, respondents were primarily concerned with running out of their triptan medication with 35% of the Delayed Treatment cohort expressing this concern compared with 22% of the Early Treatment cohort (P ≤ .001). Statistically significant differences were also noted for concerns about taking medications (P ≤ .001), side effects (P ≤ .05), expense (P ≤ .01), and taking prescription medications (P ≤ .001). CONCLUSIONS: Results build upon previously published studies and suggest that patient beliefs directly influence how migraineurs manage their migraines and have implications for patient outcomes. Such insights should be used to facilitate physician-patient communication and reinforce the need for patient-centered care to improve patient outcomes.

Randomized trial of sumatriptan and naproxen sodium combination in adolescent migraine.

BACKGROUND: Treatment of adolescent migraine remains a significant unmet medical need. We compared the efficacy and safety of 3 doses of sumatriptan and naproxen sodium (suma/nap) combination tablets to placebo in the acute treatment of adolescent migraine. METHODS: This randomized, parallel group study in 12 to 17 year olds required 2 to 8 migraines per month (typically lasting >3 hours untreated) for ≥ 6 months. Subjects entered a 12-week run-in phase, treating 1 moderate-to-severe migraine (attack 1) with single-blind placebo. Subjects reporting headache pain 2 hours after dosing were randomly assigned into a 12-week double-blind phase, treating 1 moderate-to-severe migraine (attack 2) with placebo (n = 145), suma/nap 10/60 mg (n = 96), 30/180 mg (n = 97), or 85/500 mg (n = 152). The primary end point was the percentage of subjects pain-free at 2 hours. RESULTS: The attack 2 adjusted (age; baseline pain severity) 2-hour pain-free rates were higher with suma/nap 10/60 mg (29%; adjusted P = .003), 30/180 mg (27%; adjusted P = .003), and 85/500 mg (24%; adjusted P = .003) versus placebo (10%). Posthoc primary end-point analyses did not demonstrate differences among the 3 doses or an age-by-treatment interaction. Statistically significant differences were found for 85/500 mg versus placebo for sustained pain-free 2 to 24 hours (23% vs 9%; adjusted P = .008), 2-hour photophobia-free (59% vs 41%; adjusted P = .008), and 2-hour phonophobia-free (60% vs 42%; adjusted P = .008). Analyses of other pain, associated symptoms, rescue medication use, and health outcome end points supported higher efficacy for active doses versus placebo. All active doses were well tolerated. CONCLUSIONS: All doses of suma/nap were well tolerated, providing similarly effective acute treatment of adolescent migraine pain and associated symptoms, as compared with placebo.

The development of a survey to measure completeness of response to migraine therapy.

OBJECTIVE: To assess the psychometric properties of a new patient-reported migraine instrument, the Completeness of Response Survey (CORS), which measures a comprehensive set of factors important to patients' decisions regarding the initiation and continuation of treatment. BACKGROUND: Traditionally, migraine treatments and the instruments used to demonstrate their efficacy have focused on the relief of headache pain. As new treatments emerge with the potential for more complete and consistent migraine relief, more comprehensive tools are needed to demonstrate these benefits. The CORS includes 2 modules, the static CORS, which comprehensively evaluates one treatment at one time point, and the comparative CORS, which provides a more global comparison between 2 treatments at one time point. Together, the 2 modules can measure unmet treatment needs and improvements over the course of a clinical study. METHODS: Data from an 8-site study comparing 147 patients' recent experiences with their current triptan therapy and 2 months of study treatment with a single-tablet formulation of sumatriptan/naproxen sodium were used to conduct a preliminary psychometric evaluation of the CORS. The study included both modules of the CORS, the Headache Impact Test, the revised Patient Perception of Migraine Questionnaire, and a migraine diary. RESULTS: The CORS response categories in both the static and comparative modules demonstrated limited floor or ceiling effects and few missing values (<3%). Inter-item correlations, principal components analysis (component loading range: 0.62 to 0.95), and high estimates of internal consistency (alpha range: 0.88 to 0.94) for each composite score supported the structure and proposed scoring algorithm for the static module. The pattern of correlations between the CORS static and comparative items and composites with the revised Patient Perception of Migraine Questionnaire items and subscales, as well as the relationships between responses to selected static CORS items and the migraine diary, supported the construct validity of the CORS. CONCLUSIONS: The CORS is capable of demonstrating advantages of more comprehensive migraine therapies over traditional therapies, which are primarily focused on the resolution of headache pain, by addressing the frequency and speed with which the most common migraine symptoms are resolved and patients' return to normal functioning. This research shows evidence for the value and utility for the CORS static and comparative items and components, and further evaluation is underway.

Examining the interrelationship of migraine onset, duration, and time to treatment.

OBJECTIVE: The objective of this study is to investigate migraines, both longitudinally and cross-sectionally, to understand the impact that time of treatment has on migraine duration and the patients' return to daily functioning. BACKGROUND: Several studies have explored the relationship between migraine treatment and its impact on migraine duration; however, the interrelationship of migraine onset and impact of treatment timing on migraine resolution is not completely understood. DESIGN/METHODS: Five hundred and nine migraineurs completed 1 online baseline survey and a diary survey after each of their next 3 migraines. All subjects were 18 or older and were employed full time. RESULTS: Migraine episodes treated within 1 hour were significantly shorter on average than those treated after 1 hour (9.1 hours vs 12.3 hours) (P < .05). Over-the-counter medication was the most frequently reported first-line treatment (44%) followed by an oral triptan (30%), another prescription medication (14%), and combination therapy (4%). Rescue treatment was reported in 57% of attacks. The majority of over-the-counter (69%) and another prescription (55%) treated attacks required rescue whereas only 39% of first-line triptan attacks required rescue. CONCLUSIONS: Treating migraines early with an oral triptan-containing therapy appears to be a very effective method for reducing migraine duration and preventing the need for additional medication. Our findings also suggest that physicians should spend more time educating patients how to identify migraines early. Understanding the relationship between these key factors will provide insight into appropriate treatment and management of migraines, and more importantly, equip patients with the tools necessary to improve their outcomes and overall impact on functioning.

Long-term evaluation of sumatriptan and naproxen sodium for the acute treatment of migraine in adolescents.

OBJECTIVES: To evaluate the long-term safety, tolerability, effectiveness, impact on quality of life, and medication satisfaction of sumatriptan/naproxen sodium in the acute treatment of migraine headache in adolescents. METHODS: This 12-month, multicenter, open-label, safety study was conducted in adolescents (aged 12-17 years) with an average of 2-8 migraines/month typically lasting >2 hours untreated for >6 months prior to initiation. Subjects were instructed to treat migraines as early as possible and were allowed to rescue 2 hours post dose with a single dose of a naproxen-containing product, over-the-counter pain reliever, or anti-emetics. Subjects were advised not to take a second tablet of sumatriptan/naproxen sodium without at least a 24-hour headache-free period. Safety evaluations included adverse events, laboratory tests, and vital signs and electrocardiogram evaluation. Other evaluations included freedom from pain, quality of life, and medication satisfaction. RESULTS: Of the 656 subjects enrolled, 622 (95%) treated at least 1 migraine with sumatriptan/naproxen sodium, of which 435 (70%) and 363 (58%) completed 6 and 12 months of the study, respectively. Overall, there were 12,927 exposures to sumatriptan/naproxen sodium: on average 2.5 tablets were taken per month per subject. The most common treatment-related adverse events were nausea (7%), dizziness (3%), muscle tightness (3%), and chest discomfort (3%). There were no deaths; 4 subjects had 5 serious adverse events (suicide attempt, hemolytic anemia and syncope, suicidal ideation, spontaneous abortion) unrelated to sumatriptan/naproxen sodium and resolved without sequelae. Seven percent of subjects discontinued participation in the study because of an adverse event; 5% of subjects discontinued due to lack of efficacy. Overall, 42% of the migraine attacks were pain-free within 2 hours of treatment with sumatriptan/naproxen sodium, subjects reported improvements from baseline in 2 of 3 quality of life domains over time, and were generally satisfied with the efficacy and overall treatment at the end of the study. CONCLUSION: In adolescent migraineurs, after up to 12 months and over 12,000 exposures to sumatriptan/naproxen sodium, there were no new or clinically significant findings in the safety parameters, including the frequency and nature of adverse events, as compared to the individual components or to the adverse event profile in adults. In addition, sumatriptan/naproxen sodium provided freedom from pain over time, improvements in quality of life and medication satisfaction.