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.
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.
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).
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.
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.
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.
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.
To evaluate changes from baseline in patient-reported outcomes for measures of functioning and disability among patients with migraine treated with galcanezumab or placebo.
Patients with episodic ...migraine (4-14 monthly migraine headache days) were treated with either galcanezumab (Evaluation of LY2951742 in the Prevention of Episodic Migraine EVOLVE-1: 120 mg n = 210, 240 mg n = 208; EVOLVE-2: 120 mg n = 226, 240 mg n = 220) or placebo (EVOLVE-1 n = 425; EVOLVE-2 n = 450) during 6 months of treatment. Migraine-Specific Quality of Life Questionnaire v2.1 (MSQv2.1) measured the effect of migraine on patient functioning (physical and emotional) in 3 domains, and the Migraine Disability Assessment (MIDAS) quantified headache-related disability associated with missed or reduced productivity at work or home and social events. Both were collected at baseline and during the treatment period (MSQv2.1 = monthly; MIDAS = months 3 and 6 only).
Differences in MSQv2.1 total score least squares (LS) mean change from baseline (month 4-6) for galcanezumab (120 and 240 mg, respectively) were superior to placebo (EVOLVE-1 = 7.3 and 6.7 both
< 0.001; EVOLVE-2 = 8.5 and 7.3 both
< 0.001). Differences were similar for all domain scores (
< 0.001 for both galcanezumab doses compared with placebo), were observed as early as month 1, and were sustained for 6 months for most domains. Differences of MIDAS LS mean change from baseline (month 6) for galcanezumab (120 and 240 mg, respectively) compared with placebo were: EVOLVE-1 = -6.3 (
< 0.001) and -5.2 (
= 0.002); EVOLVE-2 = -9.2 and -8.2 (both
< 0.001).
Patients with episodic migraine treated with galcanezumab reported significant and clinically meaningful improvements in daily functioning and decreased disability compared with patients who received placebo.
This study provides Class II evidence that for patients with migraine, galcanezumab (120 mg or 240 mg) given once monthly improved functioning and reduced disability.
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.
This research examines the prevalence of morbidity and mortality among people with obesity with or without prediabetes.
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.
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).
Results of this study indicate that the presence of prediabetes contributes to the development of additional morbidity and mortality in adults with obesity.
•Obesity and prediabetes are both widespread in the United States.•The study examines prevalence for those with obesity with and without prediabetes.•Both cohorts had a high morbidity and mortality burden over 5 years.•Prediabetes and obesity had significantly higher morbidity and mortality prevalence.•Prediabetes contributes to added morbidity and mortality in adults with obesity.
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.
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.
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.
Migraine is a common and disabling neurological disease associated with substantial economic burden. Among patients with migraine, it is unknown if cost differences exist when preventive migraine ...medication (PMM) switches occur.
To understand the cost burden and health care resource utilization of patients who discontinue or cycle through 1 (PMM1), 2 (PMM2), or ≥ 3 (PMM3) unique PMM drug classes over a 12-month period versus patients who adhere persistently to their initial PMM class.
This retrospective observational study used the Truven Health Analytics MarketScan databases to identify adult patients with migraine initiating their first PMM class (antidepressants, antiepileptics, beta blockers, or neurotoxins) from 2011-2013 (index date = first PMM claim). Patients were required to have ≥ 2 outpatient (1 if inpatient) migraine diagnosis codes (ICD-9-CM 346.xx) from 1 year pre-index to 1 year post-index with ≥ 1 code occurring pre-index. Inclusion criteria also required 12 months of pre- and post-index continuous medical and prescription enrollment. All-cause and migraine-specific total direct costs (outpatient, inpatient, emergency department, and prescriptions), based on the 2014 Consumer Price Index, were estimated for each PMM versus a persistent subgroup during the 12-month post-index period. Propensity score bin bootstrapping, controlling for patient baseline characteristics, was used to adjust separate cost comparisons between each PMM subgroup and the persistent subgroup; bootstrap simulations yielded propensity score-adjusted P values.
The study population included 55,402 patients who received a PMM. The study population was mainly female (85%) with a mean age of 39.2 years and mean Charlson Comorbidity Index of 0.31. Antiepileptics were the most common drug class chosen at index across all subgroups; however, lower use of antiepileptics was observed in PMM2 and PMM3 subgroups, which were more likely to be prescribed either antidepressants or beta blockers at index. Mean all-cause total direct costs, including prescription costs, were significantly higher in PMM2 ($13,429) and PMM3 ($18,394) subgroups versus the persistent subgroup ($11,941; each adjusted pairwise comparison, P < 0.001). Mean migraine-specific total direct costs were significantly lower for the persistent subgroup ($2,420) versus PMM2 and PMM3 subgroups and escalated with increasing numbers of drug class discontinuations or switches, from a mean of $2,997 to $5,004 (both adjusted pairwise comparisons, P < 0.001). Subgroup differences in all-cause and migraine-specific direct costs were primarily due to variations in outpatient and emergency department services.
All-cause total direct costs rose with increasing number of PMM switches over the 12-month post-index period, and were significantly higher than in the persistent subgroup, with the exception of PMM1. Additional analyses indicated that the lack of increase between PMM-persistent and PMM1 costs was due to higher pharmacy costs that were likely related to continuous use of medication in the PMM-persistent subgroup. These data suggest an increased cost burden among patients with migraine who cycle through ≥ 2 PMMs versus those who continue to receive their initial medication class.
Eli Lilly and Company was the sole sponsor and funder for this study and was responsible for the study design, data collection, data analysis, interpretation of data, and decision to publish the findings. All authors are employees and minor stockholders of Eli Lilly and Company. Nyhuis was employed by Eli Lilly and Company at the time of this study. The findings of this study were presented in part at the 18th Congress of the International Headache Society; September 7-10, 2017; Vancouver, Canada.
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