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.

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.

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.

Migraine Headache Day Response Rates and the Implications to Patient Functioning: An Evaluation of 3 Randomized Phase 3 Clinical Trials of Galcanezumab in Patients With Migraine.

OBJECTIVE: This post hoc study investigated the relationship between patient response in terms of migraine headache day reduction and patient-reported outcomes of health-related quality of life (HRQoL) and disability categories. BACKGROUND: Migraine causes considerable disease-related disability and negatively impacts HRQoL of patients. Calcitonin gene-related peptide inhibitors improve these outcomes and may eliminate disability due to migraine in some patients. METHODS: Analyses used data from 3 double-blind, placebo (PBO)-controlled, phase 3 studies in adults with episodic migraine (EM) (EVOLVE-1: N = 858 and EVOLVE-2: N = 915) or chronic migraine (CM) (REGAIN: N = 1113). Patients were randomized 2:1:1 to subcutaneous injection of PBO, galcanezumab (GMB) 120 mg, or GMB 240 mg once monthly for 6 months in EVOLVE-1 and -2 and for 3 months in REGAIN. Primary endpoint was overall mean change from baseline in monthly migraine headache days. Patients were divided into 4 response-level groups based on percent change from baseline (<30%, ≥30% to <50%, ≥50% to <75%, ≥75%). Patient-reported outcomes included the 14-item Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) and Migraine Disability Assessment (MIDAS) questionnaire. RESULTS: Among patients with migraine, mean improvements from baseline in MSQ domain scores increased with each successive level of migraine headache day response. On a 100-pt scale, increases in Role Function-Restrictive score in EM were 16.8 and 36.0 at the <30% and ≥75% response levels, respectively, and for CM were 10.7 and 46.5. Similar patterns in scores were observed for the Role Function-Preventive and Emotional Function domains. Examination of improvement in MSQ item score by treatment group showed that, in patients with EM, approximately 10 to 20% more GMB-treated patients (N = 796 for GMB 120 mg and GMB 240 mg) had improvements in all 14 MSQ items compared with PBO-treated patients (N = 773) (all P < .001). In patients with CM, 3 to 16% more GMB-treated patients (N = 507) had improvements in the 14 MSQ items compared with PBO (N = 494), though differences were statistically significant in only 19 of 28 comparisons. At baseline, mean MIDAS scores (EM, 33.1; CM, 67.2) indicated severe mean disability for patients with EM and very severe disability for patients with CM. Among patients with EM, 215 of 425 (50.6%) of those treated with GMB 120 mg and 212 of 413 (51.3%) treated with 240 mg had little/no disability due to migraine after 6 months (PBO: 277 of 832 (33.3%), P < .001 for both). Among patients with CM, 50 of 254 (19.7%) of those treated with GMB 120 mg and 54 of 258 (20.9%) treated with 240 mg reached the level of little/no disability after 3 months of treatment (PBO: 70 of 504 (13.9%), P = .045 for 120 mg, P = .017 for 240 mg). CONCLUSIONS: Because migraine greatly impairs an individual's ability to participate in activities of daily living, measurements of HRQoL are essential in clinical research. This study showed that function in daily life, as measured by MSQ score, improved as migraine headache days were reduced and that GMB-treated patients were more likely to see improvement in MSQ item scores compared with PBO-treated patients. Elimination of migraine-related disability was also more frequent in GMB-treated patients compared with placebo-treated patients.

Efficacy of galcanezumab in patients with chronic migraine and a history of preventive treatment failure.

BACKGROUND: Efficacy of galcanezumab in chronic migraine has been demonstrated in a pivotal Phase 3 study. Here, we assess efficacy in patients who have failed ≥2 and ≥1 prior migraine preventives for efficacy and/or safety reasons, and in those who never failed. STUDY DESIGN/METHODS: REGAIN (NCT02614261) was a Phase 3, randomized, double-blind, placebo-controlled study in patients with chronic migraine. Patients were randomized 2:1:1 to receive placebo, galcanezumab 120 mg/240 mg once monthly during a double-blind treatment period lasting three months. Subgroup analyses were conducted among patients who failed ≥2 and ≥1 prior preventives and who never failed previously. Outcomes assessed were change from baseline in number of monthly migraine headache days, proportion of patients with ≥50% and ≥75% response (reduction in monthly migraine headache days), change in number of monthly migraine headache days with acute medication use and change in patient functioning per Migraine-Specific Quality of Life Questionnaire Role Function Restrictive (MSQ RF-R) domain score. RESULTS: Treatment with galcanezumab versus placebo resulted in significant improvements (p < 0.01) in overall reduction (Months 1-3) from baseline in the number of monthly migraine headache days in patients with prior failures (LS mean change [SE]: ≥2 prior failures: galcanezumab 120 mg: -5.35 (0.71); galcanezumab 240 mg: -2.77 (0.66); placebo: -1.01 (0.54); ≥1 prior failures: galcanezumab 120 mg: -5.53 (0.60), galcanezumab 240 mg: -3.53 (0.59); placebo: -2.02 (0.49). Similarly, significant results were seen with galcanezumab versus placebo for ≥50% and ≥75% response rates, reductions in acute medication use and improvements in MSQ RF-R domain score. In the subgroup with no prior preventive failures, results were statistically significant for the 240 mg galcanezumab group versus placebo on all outcome measures, and for the 120 mg group on the reduction in migraine headache days with acute medication use. There was also a higher placebo response observed in the patients with no prior preventive failures. CONCLUSION: Galcanezumab is consistently efficacious versus placebo in reducing monthly migraine headache days and several other key outcomes in patients with chronic migraine who have failed ≥2 or ≥1 preventives previously. In the subgroup with no prior failures, greater numerical differences were seen with galcanezumab, but statistical separation from placebo varied by dose and outcome. CLINICALTRIALS.GOV IDENTIFIER NUMBER: NCT02614261.

Psychometric Validation of the Role Function Restrictive Domain of the Migraine Specific Quality-of-Life Questionnaire Version 2.1 Electronic Patient-Reported Outcome in Patients With Episodic and Chronic Migraine.

OBJECTIVES: To assess the measurement properties of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) electronic patient-reported outcome (ePRO) Role Function-Restrictive (RFR) domain to evaluate the functional impact of migraine in patients with episodic (EM) or chronic migraine (CM) enrolled in clinical trials. METHODS: The 7-item MSQv2.1 ePRO RFR measures the functional impact of migraine on relationships with family and friends, leisure time, work or daily activities, productivity, concentration, tiredness, and energy. Measurement properties of the RFR were assessed using data from 2 EM (CGAG [n = 851] and CGAH [n = 909]) and 1 CM (CGAI [n = 1090]) Phase 3 galcanezumab clinical trials. Anchor- and distribution-based analyses were utilized to derive a responder threshold for clinical interpretation of change over time. The Migraine Disability Assessment (MIDAS), Patient Global Impression of Severity (PGI-S), Patient Global Impression of Improvement (PGI-I), and migraine headache days (MHD) served as anchors. Responsiveness and responder threshold analyses were completed from baseline to the average of months 4-6 for EM studies, and from baseline to month 3 for the CM study; timeframes selected were based on the primary endpoints in these studies. RESULTS: Cronbach's alpha values for internal consistency reliability were 0.93, 0.92, and 0.92, for CGAG, CGAH, and CGAI, respectively. Test-retest reliability intra-class correlation coefficients were 0.82 and 0.84 for CGAG and CGAH, and 0.85 for CGAI in stable patients. Convergent validity was supported by moderate to strong correlations (≥0.30) between the RFR and both MIDAS and PGI-S. Known-groups validity was established between subgroups stratified by baseline PGI-S and MHD (P < .05; δ = 0.35-1.96). For the EM studies, anchor variables suggested a change of ≥25 points (equivalent to 9 points/state changes on raw scale) in the RFR was an appropriate threshold to interpret a treatment benefit. For the CM study a change of ≥17.14 points (6 points/state changes on raw scale) was an appropriate threshold. In all 3 studies, significantly (P < .01) more galcanezumab patients achieved the responder definition thresholds, as compared to placebo (odds ratios of 1.98, 2.45, 2.27, 2.44, 1.64, and 1.66 for the 120 and 240 mg arms in the CGAG, CGAH, and CGAI trials, respectively). CONCLUSION: The MSQv2.1 ePRO RFR has sufficient reliability, validity, responsiveness, and appropriate interpretation standards for use in EM and CM clinical trials to assess the functional impact of migraine.

Measures of Functioning in Patients With Episodic Migraine: Findings From a Double-Blind, Randomized, Placebo-Controlled Phase 2b Trial With Galcanezumab.

Objective - To evaluate 12-week changes from baseline of 2 disease-specific patient-reported outcome (PRO) measures in adults with migraine treated with galcanezumab, an investigational humanized antibody binding calcitonin gene-related peptide (CGRP), or placebo. Background - Preventing headache-related functional impairment is an important goal of migraine preventive treatment and a measurement target for PROs. Understanding which drugs have the potential to improve patient functioning in addition to preventing migraine headaches is vital to lessening patient burden. Design/Methods - This Phase 2b double-blind, randomized, placebo-controlled study enrolled adults with episodic migraine. Galcanezumab (120 mg subcutaneous injection; n = 60) or placebo (n = 127) was administered every 28 days for 12 weeks. Post hoc secondary analyses were conducted for those who completed 12 weeks of treatment on 2 PROs: The Migraine-Specific Quality of Life Questionnaire (MSQ) v2.1 and the Headache Impact Test™ (HIT-6). Results - Analysis of covariance revealed significant differences in least square mean changes from baseline between galcanezumab and placebo for all MSQ domains including total mean change placebo of 18.63, galcanezumab of 27.36 (95% CI 2.449, 15.008; P-value of .0067); Role Function-Restrictive mean change placebo of 22.40, galcanezumab of 31.92 (95% CI 2.636, 16.518; P-value of .0071); Role Function-Preventive mean change placebo of 13.43, galcanezumab of 19.76 (95% CI 0.476, 12.185; P-value of .0342); and Emotional Function mean change placebo of 16.88, galcanezumab of 26.61 (95% CI 2.789, 16.674; P-value of .0063). At baseline, mean number of migraine headache days (MHDs) did not correlate with MSQ total scores or HIT-6. At 12 weeks post-treatment, MHD correlated with MSQ and HIT-6 scores (all P < .0001). Change in MHD was associated with change in MSQ domains and change in HIT-6 scores (all P < .0001). Conclusions - In comparison with placebo, treatment with galcanezumab was associated with significant functional improvements as reflected by changes in MSQ scores. Change in MHD was associated with improvements in MSQ and reductions in HIT-6 scores, indicating the clinical importance of these changes in relation to PROs that measure function.

A Real-World Analysis of Migraine: A Cross-Sectional Study of Disease Burden and Treatment Patterns.

OBJECTIVE: The purpose of this cross-sectional study was to assess the sociodemographics, disease burden, and treatment patterns of patients with episodic and chronic migraine in the United States. BACKGROUND: Migraine is a disabling neurological disease that places an enormous burden on patients. METHODS: Data were drawn from the Adelphi Migraine United States Disease Specific Programme (index period: January to March 2014). Physicians (N = 150) completed a patient report form on 10 consulting patients with migraine. Episodic migraineurs had ≤14 headache days per month (HDM) and those with chronic migraine had ≥15. Headache-related disability was assessed with the Migraine Disability Assessment (MIDAS) questionnaire. Disability was also compared across subgroups based on the number of HDM (≤3, 4-7, 8-14, and ≥15). RESULTS: A total of 1487 patient report forms were completed. Over 70% of the patients were female, 90.8% (n = 1350) were episodic migraineurs, and 9.2% (n = 137) were chronic migraineurs. Acute treatment was prescribed for >90% of the patients, and >50% had a current prescription for preventive treatment. Despite taking acute and/or preventive treatment, 29.2% of episodic migraineurs (including some patients with ≤3 headache days/month) and 73.2% of chronic migraineurs had moderate-to-severe headache-related disability (MIDAS total score ≥11). Preventive treatment was discontinued/switched at least once by 26.4% of episodic migraineurs and by 53.3% of chronic migraineurs. Of those patients (n = 382) who gave collective reasons for discontinuation/switching preventive treatment, over 70% selected lack of efficacy and tolerability/safety. CONCLUSIONS: This real-world analysis provides additional support for the unmet medical need for efficacious therapies that reduce migraine frequency and severity, headache-related disability, and have better tolerability for patients with migraine. In addition, further research is needed to better understand the burden of illness among patients with lower migraine frequency, and to implement treatment strategies to prevent progression of the disease.

Economics of Inhaled Oxygen Use as an Acute Therapy for Cluster Headache in the United States of America.

BACKGROUND: Cluster headache (CH) is a primary headache disorder associated with low levels of diagnosis and high unmet medical need. The pain attacks, associated anxiety, and fear in anticipation of the attacks are extremely debilitating to a patient with CH. For acute therapy, treatment guidelines recommend inhalation of high flow oxygen during the period of an attack. However, the use of oxygen for treatment of CH remains largely underutilized. OBJECTIVES: The objectives of the study, which covered each of the US states, were to map the current market landscape of medical grade oxygen for use in CH and to develop a cost simulator based on a patient's needs and geography. METHODS: Desk research was undertaken to obtain price lists and product catalogs from wholesale and retail suppliers of medical grade oxygen across all US states. Base case scenarios for chronic and episodic forms of CH were assumed. A cost simulator was used to calculate the cost of oxygen use using inputs including the state in USA, tank size and price, exacerbations per year, duration of exacerbation, attacks per day, flow rate and duration of flow. Information was also collected to determine if healthcare insurers covered the costs of home oxygen use for CH. RESULTS: Out of the 42 US states where pricing information of medical grade oxygen was available from suppliers, in 38 states the annual cost of high-flow oxygen for a patient with episodic CH was estimated to be <$1000. In 39 states, the annual cost of high-flow oxygen for a patient with chronic CH was estimated to be <$5000. Most of the home oxygen suppliers were familiar with CH and stocked the special non-rebreather masks and regulators necessary for this condition. It was found that many of the private commercial healthcare insurance providers reimbursed the cost of oxygen use for CH. However, the US Centers for Medicare and Medicaid Services (CMS) maintains there is insufficient evidence for coverage and continues to deny coverage for US Medicare and Medicaid patients. CONCLUSIONS: Results from our study showed that the current costs for oxygen use as an acute therapy in CH are not prohibitively expensive for patients and healthcare insurance providers. Apart from CMS, many insurers do reimburse the cost of oxygen use for CH. Our study suggests that further research is needed to determine if a lack of physician awareness about treatments and ways to prescribe are barriers for patients to access the high-flow oxygen treatment.

Clinical Characteristics and Treatment Patterns Among Patients Diagnosed With Cluster Headache in U.S. Healthcare Claims Data.

OBJECTIVE: To characterize demographics, clinical characteristics, and treatment patterns of patients with cluster headache (CH). BACKGROUND: CH is an uncommon trigeminal autonomic cephalalgia with limited evidence-based treatment options. Patients suffer from extremely painful unilateral headache attacks and autonomic symptoms with episodic and chronic cycles. DESIGN/METHODS: This retrospective analysis used insurance claims from Truven Health Analytics MarketScan® research databases from 2009 to 2014. Two cohorts were compared: CH patients (with ≥2 CH claims) were propensity score matched with 4 non-headache controls, all with continuous enrollment for 12 months before and after the date of first CH claim or matched period among controls. RESULTS: CH patients (N = 7589) were mainly male (57.4%) and 35-64 years old (73.2%), with significantly more claims for comorbid conditions vs controls (N = 30,341), including depressive disorders (19.8% vs 10.0%), sleep disturbances (19.7% vs 9.1%), anxiety disorders (19.2% vs 8.7%), and tobacco use disorders (12.8% vs 5.3%), with 2.5 times greater odds of suicidal ideation (all P < .0001). Odds of drug dependence were 3-fold greater among CH patients (OR = 2.8 [95% CI 2.3-3.4, P < .0001]). CH patients reported significantly greater use of prescription medications compared with controls; 25% of CH patients had >12 unique prescription drug claims. Most commonly prescribed drug classes for CH patients included: opiate agonists (41%), corticosteroids (34%), 5HT-1 agonists (32%), antidepressants (31%), NSAIDs (29%), anticonvulsants (28%), calcium antagonists (27%), and benzodiazepines (22%). Only 30.4% of CH patients received recognized CH treatments without opioids during the 12-month post-index period. These patients were less likely to visit emergency departments or need hospitalizations (26.8%) as compared to CH patients with no pharmacy claims for recognized CH treatments or opioids (33.6%; P < .0001). CONCLUSIONS: The burden of CH is associated with significant co-morbidity, including substance use disorders and suicidal ideation, and treatment patterns indicating low use of recognized CH treatments.

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.

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.

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.

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.

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.

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.

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.