Weight management treatment modalities in patients with overweight or obesity: A retrospective cohort study of administrative claims data.

Background: The purpose of this study was to describe demographic and clinical characteristics among patients who have medical encounters for weight management treatments and to investigate the association of those characteristics with treatment modality. Methods: This was a retrospective database study using medical claims, pharmacy claims, and enrollment information from commercial and Medicare Advantage with Part D members in the Optum Research Database from 01/01/2011-2/29/2020. Adult patients with a claim for a weight management treatment from 01/01/2012-2/28/2019 were categorized into cohorts according to the highest intensity intervention received. To examine the association between patient characteristics and treatment modality received, a multinomial logit model was performed. Results: Cohorts by increasing intensity included lifestyle intervention (LSI, n = 67,679), weight reduction pharmacotherapy (WRRx) with an anti-obesity medication (AOM, n = 6,905), weight reduction procedure (WRP, n = 1,172), and weight reduction surgery (WRS, n = 18,036). Approximately 32.1% and 16.6% of patients who received WRS or WRP had an LSI during the 12-month baseline, and only 0.6% and 0.4% had treatment with long-term AOMs. In a multinomial logit model, patients with type 2 diabetes (not including WRRx cohort), respiratory disorders, cardiovascular risk factors, pain disorders, and mental health conditions had increased odds of treatment with higher intensity intervention versus LSI. Patients who were male, received an intervention more recently (2016-2019), or had a Charlson comorbidity score of 1 (compared to 0) had decreased odds of treatment with higher intensity interventions. Conclusion: In this study, age, sex, body mass index, obesity-related complications, and Charlson comorbidity score appeared to influence the type of weight management treatment modality received. This study improves understanding of weight management treatment utilization and identifies gaps and opportunities to improve obesity care with the appropriate use of different treatment modalities.

Five-year morbidity and mortality rates in a U.S. population with obesity with and without prediabetes.

AIMS: This research examines the prevalence of morbidity and mortality among people with obesity with or without prediabetes. METHODS: This observational study uses Optum® Market Clarity deidentified data from 2007 to 2020. Individuals with obesity without prediabetes (obesity only) were matched 1:1 to adults with prediabetes plus obesity based upon age, sex, race, ethnicity, and region. Age and sex adjusted prevalence rates and 95 % CIs were calculated for morbidity and mortality for each 365-day period post index date and over the entire 5-year post-period. RESULTS: After 5-years, the adjusted mortality rate was 10.1 % for adults with obesity plus prediabetes and 6.9 % for adults with obesity only (p < 0.05). Five years post index date, the prevalence of type 2 diabetes was 25.3 % for people with obesity plus prediabetes and 9.2 % for people with obesity only (p < 0.05). Prevalence rates after 5 years for atherosclerotic cardiovascular disease (13.1 % v 8.1 %), composite cardiovascular outcome (7.0 % v 4.4 %) and composite cardio-renal outcome (8.9 % v 5.0 %) were significantly higher for adults with obesity plus prediabetes compared to adults with obesity only (all p < 0.05). CONCLUSIONS: Results of this study indicate that the presence of prediabetes contributes to the development of additional morbidity and mortality in adults with obesity.

Validation and meaningful within-patient change in work productivity and activity impairment questionnaire (WPAI) for episodic or chronic migraine.

BACKGROUND: No available studies demonstrate validity and meaningful change thresholds of Work Productivity and Activity Impairment (WPAI) questionnaire in patients with migraine. In this post-hoc analysis, we assessed reliability, validity, responsiveness, and meaningful within-patient change from baseline to Month 3 for Work Productivity and Activity Impairment (WPAI) domain scores in patients with episodic migraine (EM) or chronic migraine (CM). METHOD: The Phase 3, multicenter, randomized, double-blind, placebo-controlled CONQUER study (NCT03559257, N = 462) enrolled patients with EM or CM who failed two to four categories of prior preventive medication in past ten years. The analyses were performed for WPAI domain scores (absenteeism, presenteeism, overall work productivity, and non-work-related activity impairment). Migraine Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) domain scores (Role Function-Restrictive [RFR] and Role Function-Preventive [RFP]), and monthly migraine headache days were used as anchors. Responder criteria were changes from baseline to Month 3 for each of these anchors and were defined as: increase in MSQ-RFR by ≥ 25.71 points and MSQ-RFP by ≥ 20.00 points and a 50% reduction in monthly migraine headache days. Assessments were performed for overall population, and patients with EM or CM. The meaningful change threshold was determined based on Youden index, Phi coefficient and sensitivity. RESULTS: Of 462 randomized patients, 444 who completed WPAI questionnaire were included in post-hoc analysis. Test-retest reliability over 3 months in a stable subgroup revealed moderate correlations for non-work-related Activity Impairment (ICC = 0.446) presenteeism (ICC = 0.438) and a fair correlation for overall work productivity loss (ICC = 0.360). At baseline, all correlations between WPAI domain scores and continuous anchor variables exceeded recommended threshold of ≥ 0.30, except for WPAI domain scores with number of monthly migraine headache days. Patients achieving pre-specified responsiveness thresholds for monthly migraine headache days, and MSQ-RFP, MSQ-RFR from baseline to Month 3 (responders) showed significant improvements in WPAI domain scores compared with non-responders (P < 0.001). The meaningful change thresholds of -20 (% unit) were identified for WPAI domain scores. CONCLUSION: In conclusion, WPAI has sufficient validity, reliability, responsiveness, and appropriate interpretation standards to assess the impact of EM or CM on presenteeism and overall work productivity loss and non-work-related activity impairment. TRIAL REGISTRATION: NCT number of CONQUER study, NCT03559257.

Changes in migraine interictal burden following treatment with galcanezumab: Results from a phase III randomized, placebo-controlled study.

OBJECTIVE: To evaluate changes in interictal burden with galcanezumab versus placebo in patients with episodic (EM) or chronic migraine (CM). BACKGROUND: The disruptive effects of migraine occur both during attacks (ictal period) and between attacks (interictal period), affecting work, school, family, and social life. Migraine clinical trials typically assess ictal burden endpoints, neglecting interictal burden. METHODS: CONQUER was a 3-month, double-blind study that randomized adult patients with EM or CM who had experienced failure of two to four standard-of-care migraine preventive medication categories to receive monthly galcanezumab (n = 232) or placebo (n = 230), followed by 3 months of open-label galcanezumab. The mean change in interictal burden, a secondary objective, was measured using the four-item Migraine Interictal Burden Scale (MIBS-4). The total score for MIBS-4 can range from zero to 12, with scores ≥5 indicating severe interictal burden. Post hoc analyses evaluated shifts in MIBS-4 severity categories and item-level improvement. RESULTS: The MIBS-4 total score indicated severe interictal burden at baseline (mean [SD]: all patients, 5.5 [3.5]; EM, 5.0 [3.4]; CM, 6.2 [3.5]). Reductions in the MIBS-4 score were significantly greater with galcanezumab versus placebo at Month 3 (mean [SE]: all patients -1.9 [0.2] vs. -0.8 [0.2], p < 0.0001; EM, -1.8 [0.3] vs. -1.1 [0.3], p = 0.033; CM, -1.8 [0.4] vs. -0.3 [0.4], p < 0.001), with further improvement at Month 6 after all patients had received galcanezumab (mean [SE]: all patients, -2.4 [0.2] vs. -2.0 [0.2]; EM, -2.3 [0.3] vs. -2.2 [0.3]; CM, -2.1 [0.4] vs. -1.5 [0.4]). The percentage of patients with severe interictal burden decreased substantially for the galcanezumab-treated patients, from 59% (137/232) at baseline to 27% (58/217) at Month 6 (EM from 51% [70/137] to 23% [30/131]; CM from 71% [67/95] to 33% [28/86]). CONCLUSION: In addition to the known efficacy of galcanezumab in the ictal period, these findings suggest treatment with galcanezumab results in a significant reduction in interictal burden.

Real-World Treatment Patterns and Outcomes Among Patients with Episodic Migraine in China: Results from the Adelphi Migraine Disease Specific Programme™.

Objective: This study assessed treatment patterns, disease burden, outcomes, and unmet needs among patients with episodic migraine (EM) in China using Adelphi Migraine Disease Specific Programme™ (DSP) real-world data. Background: Migraine is a prevalent and debilitating neurological disorder which presents a major public health burden globally. Research on characteristics, disease burden, and treatment patterns in EM patients in China is limited. Methods: Data were drawn from an existing data set Adelphi Migraine DSP, a point-in-time survey conducted in China (January-June 2014). Internists/neurologists completed patient record forms for the next 9 patients who consulted them in clinical practice; these same patients completed the 'patient self-completion questionnaires'. Descriptive analyses were used to assess key variables: patient demographics, treatment patterns (current acute and preventive medication [AM/PM]), effectiveness, issues with existing treatment, Migraine Disability Assessment (MIDAS) scores, and Work Productivity and Activity Impairment scores. Results: Total of 125 internists/neurologists provided data on 1113 patients with EM (headache days/month <15). Mean (standard deviation [SD]) age was 43.8 (13.1) years; mean (SD) number of migraine days/month was 3.2 (1.7). AM was prescribed in 86.1% of patients (non-steroid anti-inflammatory drugs [NSAIDs]: 62.7%; triptans: 7.7%), PM in 38.5%, and both in 24.9% of patients. Approximately 55% of patients experienced ≥1 issue with their current AM or PM. Migraine-related symptoms (including nausea, photophobia, and phonophobia) were fully controlled in <50% of patients receiving NSAIDs (21.7-38.4%) or triptans (32.4-43.5%). Insufficient response to current AM (migraine headache fully resolved within 2 hours in ≤3/5 attacks) was reported by 42.5% of patients. Mild-to-severe disability was reported by 36.8% of patients with a mean (SD) MIDAS score of 5.8 (7.3). Overall, 58.0% of work time was impaired (including time missed and impairment while working). Conclusion: This analysis suggests, despite existing treatment options, disease burden and unmet medical needs remain substantial in Chinese patients with EM.

The Association Between Obesity and the 5-Year Prevalence of Morbidity and Mortality Among Adults with Type 2 Diabetes.

INTRODUCTION: This retrospective claims database study examined the prevalence of mortality and morbidity among adults with type 2 diabetes (T2D) and obesity. METHODS: The study used deidentified data from 2007 to 2021 from the Optum® Market Clarity Dataset. A cohort of adults with T2D and obesity were identified, and age- and sex-adjusted prevalence rates were calculated for mortality, a composite cardiovascular outcome (CCO), a composite microvascular outcome (CMO), and other complications. Results were examined overall and by obesity class (class 1, class 2, and class 3). RESULTS: For the 15,970 adults included in the study, the prevalence of CCO and CMO after 5 years was 15.3% and 60.7%, respectively. The 5-year prevalence of mortality was 10.9%. There were statistically significant differences in prevalence rates by obesity class, with obesity class 3 associated with higher rates of morbidity and mortality compared to obesity classes 1 or 2. Specifically, after 5 years, the prevalence of mortality was 9.4%, 10.3% and 13.6% for obese classes 1, 2 and 3, respectively (P < 0.05 between class 3 and class 2 or 1). Similarly, For obesity classes 1, 2 and 3, the 5-year prevalence of CCO was 13.0%, 14.5% and 18.4% and the rates for CMO were 58.0%, 57.9% and 64.8%, respectively (both P < 0.05 between class 3 and class 2 or 1). Regarding other complications, differences in the prevalence of atherosclerotic cardiovascular disease (ASCVD) and obstructive sleep apnea (OSA) were statistically significantly higher with increasing obesity class. CONCLUSIONS: The results indicate that for a cohort of adults with T2D and obesity, obesity class 3 is associated with significantly higher mortality and morbidity, including CCO, CMO, ASCVD and OSA. These findings suggest that treatment which reduces obesity among individuals with T2D may have significant health benefits, although additional studies are needed to confirm the results.

Reductions in acute medication use and healthcare resource utilization in patients with chronic migraine: a secondary analysis of a phase 3, randomized, double-blind, placebo-controlled study of galcanezumab with open-label extension (REGAIN).

AIMS: To analyze secondary objectives of the REGAIN study related to acute headache medication use and healthcare resource utilization (HCRU) in patients with chronic migraine treated with galcanezumab, a monoclonal antibody to calcitonin gene-related peptide. METHODS: Adults with chronic migraine (N = 1,113) were randomized (2:1:1) and treated with double-blind monthly injections of placebo, galcanezumab-120 mg, or galcanenzumab-240 mg for 3 months, followed by a 9-month open-label extension with 120 or 240 mg/month galcanezumab. Headache and medication information was collected by daily eDiary. HCRU was reported for the 6 months before randomization, monthly thereafter, and converted to rate per 100-patient-years. RESULTS: At baseline, 63-64% of patients met criteria for acute headache medication overuse. At Month 3, incidence of headache medication overuse in the galcanezumab groups (33% and 33%) was significantly lower than in the placebo group (46%, both p < .001) and was 16% and 23% in the previous-galcanezumab groups at Month 12. From a baseline of 14.5 to 15.5, reduction in mean number of monthly migraine headache days with acute headache medication use was also significantly greater in the galcanezumab groups at Month 3 (-4.2 and -4.9) than in placebo (-2.6, both p < .001), with reductions of -6.8 and -7.6 in the previous-galcanezumab groups at Month 12. Migraine-specific HCRU rates decreased for all groups, with no significant between-group differences at Month 3. At Month 12, in the two previous-galcanezumab groups, emergency room visits decreased by 58% and 75%, hospital admissions by 100%, and healthcare professional visits by 54% and 67%. LIMITATIONS: Only 3 months of double-blind, placebo-controlled data, a longer HCRU recall period for baseline than postbaseline, and patients receiving care in the clinical trial itself, may limit generalizability. CONCLUSIONS: Treatment with galcanezumab resulted in significant reductions in headache medication overuse and migraine headache days requiring acute medication use, with notable reductions in migraine-specific HCRU.

Annual indirect cost savings in patients with episodic or chronic migraine: post-hoc analyses from multiple galcanezumab clinical trials.

AIM: This post-hoc analysis estimated annual indirect cost savings with galcanezumab (GMB) treatment in patients with episodic migraine (EM) or chronic migraine (CM). METHODS: Data from 4 randomized, Phase 3, double-blind (DB), placebo (PBO)-controlled studies of GMB were analyzed: EVOLVE-1 and EVOLVE-2 (EM, 6-months DB), REGAIN (CM, 3-months DB), and CONQUER (previous failure of 2-4 migraine preventive medication categories, 3-months DB). Indirect costs were calculated at baseline and Month 3 using the first 2 items in Migraine Disability Assessment (MIDAS): (A + B)/60*country specific annual wage (A = days of missed work/school; B = days of reduced productivity at work/school; assuming 60 working days in 3 months). All costs were annualized and expressed in international dollars (Int$) in 2018. ANCOVA models estimated the indirect cost savings as a change from baseline. Secondary analyses determined cost savings by employment and responder status. RESULTS: Patients (>80% females) from EVOLVE-1 and -2 (n = 1,201; mean age 41.9 years), REGAIN (n = 759; mean age 41.3 years), and CONQUER (n = 453; mean age ∼46.0 years) were analyzed. GMB showed significant indirect cost savings for EM (Int$6256, p < .0001) and CM (Int$7129, p = .0002), with substantial savings for patients with previous failure of 2-4 migraine preventive medication categories (EM: Int$5664, p = .0030; CM: Int$5181, p = .1300). Compared with PBO, GMB showed significantly greater indirect cost savings for EM (p = .0156) and patients with previous failure of 2-4 migraine preventive medication categories (p = .0340). Employed patients with CM (p = .0018) and with previous failure of 2-4 migraine preventive medication categories (p < .0001) had significant cost savings after GMB treatment. GMB showed significant indirect cost savings in patients with a reduction in migraine headache days. CONCLUSION: GMB treatment resulted in annual indirect cost savings in patients with EM, CM, and with previous failure of 2-4 migraine preventive medication categories, with similar observations in the sensitivity analyses.

Barriers to the Provision of Preventive Care to People Living with Mental Health Conditions: Self-Report by Staff Working in an Australian Community Managed Organisation.

People living with mental health conditions experience a reduced life expectancy largely due to a higher prevalence of chronic diseases. Addressing health risk behaviours, including tobacco smoking, inadequate nutrition, harmful alcohol consumption, and physical inactivity (SNAP), through the provision of preventive care, is recommended to reduce this burden. Community Managed Organisations (CMOs) may play an important role in providing preventive care to consumers with mental health conditions, however, few studies have examined preventive care provision in CMO settings; and no studies have comprehensively assessed barriers to the provision of this care using a tool such as the Theoretical Domains Framework (TDF). To fill this research gap, we conducted an online survey among staff (N = 190) from one CMO in Australia to (1) identify barriers to preventive care provision (ask, advise, assist, connect) to address SNAP behaviours among consumers; and (2) explore associations between barriers and preventive care provision. Results demonstrate that while staff reported knowing how to provide preventive care and believed it would positively impact consumers; barriers including confidence in providing this care and consumer uptake of referrals, were identified. Further research among multiple CMOs is needed to identify care provision and associated barriers in the sector more widely.

Changes in acute headache medication use and health care resource utilization: Results from a randomized, double-blind, placebo-controlled clinical trial evaluating galcanezumab in adults with treatment-resistant migraine (CONQUER).

BACKGROUND: Patients with migraine, particularly with multiple prior preventive treatment failures, often have high rates of acute headache medication use and are at risk for overuse (acute or symptomatic headache medication use between 10 and 15 days per month [depending on the medication] for > 3 months). Furthermore, these patients have greater health care resource utilization (HCRU). OBJECTIVE: To examine acute headache medication use and HCRU with galcanezumab compared with placebo in a population with multiple prior migraine preventive treatment failures. METHODS: In the 3-month double-blind phase, patients with episodic or chronic migraine and treatment failures to 2 to 4 standard-of-care migraine preventive categories (lack of effectiveness or safety/tolerability) received galcanezumab 120 mg/month (following a 240-mg loading dose) or placebo; an optional 3 month open-label phase followed. Acute headache medication use (monthly days with acute headache medication utilization) was self-reported daily. The change from baseline in monthly days with acute headache medication used a mixed-model repeated measures analysis. HCRU was reported at baseline (for the previous 6 months) and at monthly visits. Migraine-related HCRU rates were evaluated in the total population per 100 patient-years. RESULTS: Of the 462 patients (galcanezumab n=232, placebo n=230), baseline mean days/month of acute headache medication was 12.3; 44.8% had acute headache medication overuse. Across months 1-3, least squares (LS) mean reductions in acute headache medication use were greater for the galcanezumab group (4.2) compared with placebo (0.9); the LS mean difference was 3.4 (95% CI = 2.7-4.1; P < 0.0001). Greater reductions in the galcanezumab group were observed as early as month 1; statistical separation continued at months 2 and 3 (all P < 0.0001). During the open-label phase, reductions from baseline ranged from 4.7 to 5.3 days and were similar in patients who transitioned from placebo to patients continuing galcanezumab. Reductions from baseline of migraine-specific health care visits (double-blind phase) were numerically greater with galcanezumab than placebo (215.5 vs 155.3). Patients switching to galcanezumab had reductions (212.9 days) similar to patients continuing galcanezumab (222.6 days). Migraine-specific emergency department visits decreased by two-thirds at month 3 in the galcanezumab group compared with nearly no reduction in the placebo group that experienced a similar reduction during the open-label phase. For both groups, migraine-specific hospitalizations were less than 2 per 100 patient-years. CONCLUSIONS: These results demonstrate that galcanezumab has the potential to reduce acute headache medication use and overuse and HCRU in patients with prior migraine preventive treatment failures. DISCLOSURES: Data were presented in part as a poster presentation at the 14th European Headache Congress (European Headache Federation), Virtual Meeting, July 3-5, 2020. Dr Ambrosini is on the advisory board for Eli Lilly and Company and received honorarium from Teva, Novartis, and Eli Lilly and Company. Dr Estemalik is on the advisory boards for Eli Lilly and Company, Lundbeck, and Allergan and the speakers' bureau for Teva, Lundbeck, Eli Lilly and Company, Allergan, and Biohaven. He received consulting fees from Eli Lilly and Company, Teva, Lundbeck, and Allergan and support for attending meetings and/or travel from Eli Lilly and Company, Allergan, Biohaven, Teva, and Lundbeck. Dr Pascual received research support from Instituto de Salud Carlos III, Ministry of Economy, Spain. He was also on advisory boards for Allergan, Amgen-Novartis, Eli Lilly and Company, and Stendhal and received consulting fees or honoraria from Allegan, Eli Lilly and Company, Novartis-Amgen, and Teva. Dr Rettiganti is an employee of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN. She is also a minor stock and restricted stockholder of Eli Lilly and Company. Mr. Stroud and Ms. Day are employees of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN. Dr Ford is an employee of and holds stock of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN. She also received support for attending meetings and/or travel from Eli Lilly and Company.

Effects of Galcanezumab on Health-Related Quality of Life and Disability in Patients with Previous Failure of 2-4 Migraine Preventive Medication Categories: Results from a Phase IIIb Randomized, Placebo-Controlled, Multicenter Clinical Trial (CONQUER).

BACKGROUND AND OBJECTIVES: Patients with migraine and prior preventive treatment failures have a significant burden on quality of life and disability. The CONQUER study evaluated the effects of galcanezumab on patient functioning, disability, and health status in episodic or chronic migraine with a previous failure of two to four migraine preventive medication categories. METHODS: Patients with two to four preventive migraine treatment category failures received galcanezumab 120 mg/month (240-mg loading dose) or placebo subcutaneously, for 3 months (double-blind period). In the 3-month open-label period, all patients received galcanezumab irrespective of the treatment received in the double-blind period. Changes in Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ), Migraine Disability Assessment (MIDAS), and European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) scores were assessed. RESULTS: A total of 462 patients were randomized to receive galcanezumab (N = 232) or placebo (N = 230). At month 3, improvement in the MSQ Role-Function-Restrictive score from baseline was significantly greater for galcanezumab (23.19 ± 1.34) vs placebo (10.66 ± 1.33) [p ≤ 0.0001]. Significant improvements in remaining MSQ domains and total MSQ scores were observed (p < 0.0001) during the double-blind period. MIDAS total scores were significantly (p ≤ 0.0001) reduced with galcanezumab (- 21.10 + 3.32) vs placebo (- 3.30 + 3.28). EQ-5D-5L visual analog scale scores improved for galcanezumab (3.40 + 1.31) vs placebo (- 0.09 + 1.29; p = 0.028). During the open-label period, quality of life continued to improve for galcanezumab, with patients previously assigned to placebo reaching similar results. During both study periods, similar findings were reported in subpopulations with episodic migraine and chronic migraine. CONCLUSIONS: Galcanezumab significantly improved functioning and reduced disability in patients with episodic migraine and chronic migraine and two to four migraine preventive treatment category failures. CLINICAL TRIAL REGISTRATION: NCT03559257, registration date: 6 June, 2018.

Patient Perspectives and Experiences of Preventive Treatments and Self-Injectable Devices for Migraine: A Focus Group Study.

BACKGROUND: Although several self-injectable preventive treatments for migraine have become available, they are not yet widely used. Thus, understanding patients' perceptions towards them is limited. OBJECTIVE: This study aimed to inform the design of a preference-elicitation instrument, which is being developed to quantify preventive treatment preferences of people with migraine. METHODS: We conducted a qualitative study involving nine in-person focus groups (three per country) in the United States, the United Kingdom, and Germany. Participants were adults (n = 47) with episodic or chronic migraine who were currently using or had used a prescription preventive treatment for migraine within the previous 5 years. During the focus groups, participants described their experiences of migraine and preventive treatments; handled and simulated self-injection using five different unbranded, fired demonstration auto-injectors and prefilled syringes; and ranked different aspects of preventive treatments by importance. Focus groups were analyzed with a focus on themes that would be feasible or meaningful to include in a subsequent preference-elicitation instrument. RESULTS: Reducing the frequency and severity of migraine attacks was consistently ranked as the most important aspect of preventive treatment. Participants expressed dissatisfaction with available daily oral preventive treatments for migraine they had previously used because they were ineffective or caused intolerable adverse events. Many participants were willing to self-inject a treatment that was effective and tolerable. When presented with devices for self-injecting a preventive treatment for migraine, participants generally preferred autoinjectors over prefilled syringes. Participants especially valued safety features such as the unlocking step and automated needle insertion, and audible and visual dose confirmation increased confidence in autoinjector use. Autoinjector needle protection mechanisms were also appreciated, especially by participants averse to needles, as the needles are not visible. CONCLUSIONS: This study highlights the fact that many people with migraine still lack access to a preventive treatment that is effective and tolerable. In addition to efficacy and safety considerations, treatment decisions may be guided by the mode of administration. In the case of self-injectable preventive treatments, key device characteristics affecting these decisions may be ease of use, comfort, and confidence in self-injection. Insights gained from this study were used to help develop a preliminary set of attributes and levels for a preference-elicitation instrument.

Direct cost and healthcare resource utilization of patients with migraine before treatment initiation with calcitonin gene-related peptide monoclonal antibodies by the number of prior preventive migraine medication classes.

OBJECTIVE: This study compared all-cause direct cost and healthcare resource utilization (HCRU) among preventive migraine medication (PMM)-naïve patients and patients with up to 3 PMM category switches before initiating calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). METHODS: This was a retrospective analysis of the IBM Marketscan database. Patients who initiated injectable CGRP mAbs between May 2018 and December 2019 (index period) were included in 4 groups based on the number of prior non-CGRP PMM classes used during the 24-month pre-index period: P0 = none; P1 = one; P2 = two; P3 ≥ three. All-cause direct cost and HCRU for groups were compared without adjustment and after generalized propensity score (GPS) matching. RESULTS: Of the 23,288 patients included (mean age ± standard deviation [SD] 45.4 ± 12.0 years), 85.6% were females, and the mean Charlson Comorbidity Index was 0.69 ± 1.2. P3 group had the highest average annual unadjusted total healthcare costs per patient ($50,274±$76,629); the highest costs attributed to procedure/imaging-related expenses ($20,105±$36,401) and pharmacy ($11,633±$29,763). P0 group had the lowest cost ($25,288±$41,427). Pairwise comparison of GPS matched costs showed significantly greater average annual direct costs per patient in the P3 group vs. P0 (p = .003), P1 (p = .014), and P2 (p = .021) groups. GPS matched HCRU also increased with the number of prior PMM classes used. Anti-epileptics (48.9%) were the most commonly used PMM class, with triptans (75.2%) being the most common acute medication class. CONCLUSIONS: Total direct healthcare cost and HCRU increased significantly with increasing use of PMM classes with the greatest cost difference existing between the P0 and the P3 groups.

Medications used for the prevention of migraine (PMM) are underused as they might cause adverse effects, intolerance, or may lack efficacy. This leads to the discontinuation of the current treatment and switching to other treatments. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are a new class of drugs for the prevention of migraine. Since 2018, four CGRP mAbs have been approved for use in the prevention of migraine. It is known that patients who use more preventive migraine treatments incur greater total direct (caused by a number of medical visits or increased healthcare resource utilization, surgery, drugs, equipment, etc.) annual healthcare costs and healthcare resource utilization (HCRU) in patients with migraine. In the current study, the annual average direct cost and HCRU were compared between patients who had not used preventive medicine and patients who had used 1, 2, or ≥3 preventive medicines for migraine before starting CGRP mAbs. We observed that the healthcare costs and HCRU increased with the use of a higher number of preventive medicines for migraine. Patients who started using injectable CGRP mAbs after at least 3 preventive medicines had the highest healthcare costs and HCRU compared with other groups.

Patient-Reported Outcomes for Migraine in the US and Europe: Burden Associated with Multiple Preventive Treatment Failures.

PURPOSE: To evaluate patient-reported outcomes (PROs) among patients with migraine, including those who were preventive-naïve 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 (DSP™). 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-naïve and preventive-treated patients defined by the number of treatment lines (1-2 or 3+ preventive regimens). Continuous variables were compared using t-test 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 (±14) years; 65% in full- or part-time employment). Of these, 2798 completed a PSC (preventive-naïve/1-2/3+ preventive lines, n=1707/1034/57). Preventive-treated patients had a greater patient-reported burden across multiple measures versus preventive-naïve 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-naïve 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.

Psychometric validation and meaningful within-patient change of the Migraine-Specific Quality of Life questionnaire version 2.1 electronic patient-reported outcome in patients with episodic and chronic migraine.

OBJECTIVE: To evaluate the measurement properties of all three domains of the Migraine-Specific Quality of Life questionnaire version 2.1 (MSQ v2.1) electronic patient-reported outcome (ePRO) to assess the functional impact of migraine in patients with episodic or chronic migraine (CM); and identify meaningful within-patient change thresholds for the Role Function-Restrictive (RFR), Role Function-Preventive (RFP), and Emotional Function (EF) domains. METHODS: Data were drawn from three double-blind, placebo-controlled, and randomized Phase 3 clinical studies (episodic migraine [EM]: EVOLVE-1 and EVOLVE-2; CM: REGAIN). The psychometric properties of the MSQ v2.1 ePRO domains were demonstrated by evaluating reliability (internal consistency and test-retest), construct validity (convergent and known groups), and responsiveness. Meaningful within-patient change thresholds for domains were estimated using anchor-based approaches, supplemented by empirical cumulative distribution function curves and probability density function plots to enable interpretation of meaningful change over 3 months. The Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Improvement served as anchors. RESULTS: A total of 2,850 patients with either EM (EVOLVE-1: 851; EVOLVE-2: 909) or CM (REGAIN: 1,090) were included. The Cronbach's alpha estimates of internal consistency exceeded the recommended threshold of ≥0.70 for all domains from the three studies, indicating adequate internal consistency. Test-retest reliability intraclass correlation coefficients were ≥0.80 for all domains across all three studies, demonstrating almost perfect agreement. Convergent validity was supported by moderate-to-strong correlation (r ≥ 0.30) between all domains of MSQ v2.1 ePRO and studied anchors (Migraine Disability Assessment Score and PGI-S scores) across all three studies. Known group validity was established between all domains and subgroups of patients stratified by baseline PGI-S scores and baseline number of monthly migraine headache days for all three studies. The 3-month meaningful within-patient change thresholds were the same for EM and CM for RFP: 20.00 and EF: 26.67; and for RFR: 25.71. CONCLUSIONS: These findings demonstrate that all three domains of the MSQ v2.1 ePRO have sufficient reliability, validity, responsiveness, and appropriate interpretation standards. Our results suggest that MSQ v2.1 ePRO is a well-defined and reliable patient-reported outcome instrument that is suitable for use in clinical studies for evaluating the impact of migraine on patient functioning in episodic and CM.

Trends in Depressed Mood and Suicidal Behaviors Among Female High School Students Who Engaged in Physical Fighting.

The objective of this article is to identify prevalence changes in depressed mood/suicidal behaviors among female high school students reporting physical fighting. This research analyzed the national combined data set of the Youth Risk Behavior Surveillance (YRBS) cross-sectional surveys from 2001 to 2015. Logistic regression analyzed the time trends. Two multiple logistic regression models were built. A quadratic trend was present with an initial decrease followed by an increase 2009 to 2015 (p < .001). The odds and severity of depressed mood/suicidal behaviors were greater among female youths with four or more fights and for other violent events, which were even greater when accounting for electronic bullying. The odds of depressed mood/suicidal behaviors among female adolescents engaged in physical fighting has been increasing with electronic bullying contributing to polyvictimization.

Changes in patient functioning and disability: results from a phase 3, double-blind, randomized, placebo-controlled clinical trial evaluating galcanezumab for chronic migraine prevention (REGAIN).

PURPOSE: To evaluate secondary outcomes including changes in functioning and disability associated with galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, in patients with chronic migraine. METHODS: Patients randomly received galcanezumab (120 mg n = 278, 240 mg n = 277) or placebo (n = 558) during 3 months of double-blind treatment, followed by a 9-month open-label extension. The Migraine-Specific Quality-of-Life Questionnaire v2.1 (MSQv2.1) measured the impact of migraine on patient functioning. The Migraine Disability Assessment (MIDAS) quantified headache-related disability. Changes from baseline were analyzed with mixed model repeated measures or analysis of covariance. RESULTS: Total MSQ score at baseline was 44.88 ± 18.02 (mean ± SD), indicating significant functional impairment. At Month 3, least squares (LS) mean change ± SE in total MSQ for galcanezumab-treated patients were 20.51 ± 1.49 (120 mg) and 20.49 ± 1.49 (240 mg), both statistically significantly greater vs placebo-treated patients (14.55 ± 1.21; both P < 0.001). Total MIDAS score at baseline was 67.24 ± 57.31 (mean ± SD). At Month 3, LS mean change ± SE from baseline in total MIDAS for galcanezumab-treated patients was statistically significantly greater than placebo for 120 mg group (placebo: - 11.53 ± 3.38 vs 120 mg: - 20.27 ± 4.07; P < 0.05) but not for 240 mg group (- 17.02 ± 4.05). At Month 12, within-group mean changes from baseline for total MSQ (28.56 ± 1.19 previous placebo; 29.53 ± 1.51 previous 120 mg; 25.83 ± 1.49 previous 240 mg) and MIDAS scores (- 28.47 ± 2.95 previous placebo; - 31.47 ± 3.69 previous 120 mg; - 31.13 ± 3.62 previous 240 mg) were statistically significant (P < 0.001) for the open-label treatment population regardless of previous double-blind treatment assignment. CONCLUSIONS: Galcanezumab-treated patients with chronic migraine reported statistically significant improvements in functioning and disability, representing a clinically significant change. TRIAL REGISTRATION: ClinicalTrials.gov registry: NCT02614261. Registered 25 November 2015.

Functional impairment and disability among patients with migraine: evaluation of galcanezumab in a long-term, open-label study.

PURPOSE: Migraine can negatively impact patient functioning and quality of life. Here, we report the effects of galcanezumab (GMB), a humanized monoclonal antibody that binds to calcitonin gene-related peptide, on patient-reported outcome (PRO) measures in migraine. METHODS: CGAJ was a Phase III, randomized, open-label study (12-month open-label and 4-month post-treatment follow-up) in patients with episodic or chronic migraine. Patients aged 18-65 years with diagnosis of migraine (≥ 4 migraine headache days per month) as defined by International Classification of Headache Disorders (ICHD)-3 beta guidelines were included in the study. Patients were randomized 1:1 with subcutaneous GMB 120 mg (with a loading dose of 240 mg) or GMB 240 mg given once monthly for 12 months. Changes from baseline in PRO measures such as Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ) and Migraine Disability Assessment (MIDAS) were assessed. RESULTS: A total of 135 patients were randomized to each galcanezumab dose group. Mean (SD) baseline MSQ total scores were 53.85 (20.34) [GMB 120 mg] and 53.69 (18.79) [GMB 240 mg]. For MIDAS, mean (SD) total scores were 45.77 (42.06) [GMB 120 mg] and 53.96 (61.24) [GMB 240 mg]. Within-group mean improvement from baseline on MSQ and MIDAS total scores and all individual item/domain scores were statistically significant for both GMB dose groups, at all-time points during the treatment phase (p < 0.001). For MSQ domain scores, greatest improvement was observed in the Role function-restrictive (RF-R) domain (overall least squares (LS) mean change ± SE: 31.55 ± 1.20 [GMB 120 mg] and 33.40 ± 1.16 [GMB 240 mg]). For MIDAS, the overall LS mean change ± SE from baseline across the entire 12-month treatment phase in total scores were: -33.58 ± 2.11 (GMB 120 mg) and -32.67 ± 2.04 (GMB 240 mg). CONCLUSION: Galcanezumab was associated with statistically significant changes from baseline in the PRO measures across the entire 12-month treatment period. These results indicate improved health-related quality of life and decreased disability among patients treated with galcanezumab.