Highlights
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The total mean direct healthcare cost of migraine was 1.5 times higher than matched controls, with a predicted incremental cost of $2,806 per person per year.
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Prescription medication was the primary cost driver.
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Migraine may account for an additional $1.05–1.29 billion in healthcare costs per year in Alberta.
Introduction
Migraine is a common neurological disorder characterized by recurrent headaches that are moderatetosevere in nature and lead to significant symptoms and disability. Reference Steiner, Stovner, Jensen, Uluduz and Katsarava1,Reference Steiner, Stovner, Vos, Jensen and Katsarava2 The 2021 Global Burden of Disease study ranked migraine as the second-leading disabling neurological condition in North America. 3 Migraine can be classified as episodic and chronic – episodic migraine (EM) is defined as having <15 headache days per month, and chronic migraine (CM) is defined as headache occurring on ≥15 days per month for >3 months that has the features of migraine headache on ≥8 days per month. 4 Based on data from the Canadian Community Health Survey, between 8.3% and 10.2% of Canadians have reported being diagnosed with migraine by a health professional, of whom females indicated having migraine more than twice as often as males. Reference Graves, Gerber and Berrigan5,Reference Ramage-Morin and Gilmour6 CM is less prevalent than EM, with estimates typically in the range of 1.4%–2.2% of the general population. Reference Natoli, Manack and Dean7
Previous studies have shown that persons living with migraine have higher healthcare resource use and costs than those not living with migraine. Reference Wolfson, Fereshtehnejad, Pasquet, Postuma and Keezer8–Reference Gilligan, Foster, Sainski-Nguyen, Sedgley, Smith and Morrow11 Additionally, those living with CM consistently display higher healthcare resource use and costs compared with those living with EM. Reference Messali, Sanderson and Blumenfeld12–Reference McMullen, Graves, Ekwaru, Pham, Mayer, Ladouceur, Hubert, Bougie and Amoozegar15 However, relatively few studies have been conducted on the healthcare cost of persons living with migraine, including CM and EM, in Canada. Reference Stokes, Becker and Lipton13–Reference Graves, Cowling and McMullen16 Two recent administrative data claims-based studies described the direct healthcare costs of adults with newly diagnosed/recurrent migraine, including CM and EM, in Alberta. Reference McMullen, Graves, Ekwaru, Pham, Mayer, Ladouceur, Hubert, Bougie and Amoozegar15,Reference Graves, Cowling and McMullen16 The authors found that during a follow-up period, the total mean annual direct healthcare cost of adults living with migraine was $6,403 per person (included costs: all-cause hospitalization, emergency department [ED], non-emergent ambulatory care, physician, diagnostic imaging and migraine-related medication); CM was $12,693, and EM was $4,251 per person (2020 Canadian dollars [$CDN]). Reference McMullen, Graves, Ekwaru, Pham, Mayer, Ladouceur, Hubert, Bougie and Amoozegar15,Reference Graves, Cowling and McMullen16 The additional cost that persons living with migraine may impose on the healthcare system compared with those not living with migraine that accounts for confounders remains to be elucidated within the Canadian healthcare system. The objective of this study was to compare total and incremental direct healthcare costs between adults living with migraine, including CM and EM, and those not living with migraine in Alberta, Canada; costs were also compared between CM and EM.
Methods
Ethics approval was received from the University of Alberta Research Ethics Board (Pro00083495) that granted an exemption from requiring written informed consent (a waiver of consent was applied). Data custodian approvals were received from Alberta Health and Alberta Health Services for the use of administrative health data for this study. This study was reported according to the Reporting of Studies Conducted Using Observational Routinely-Collected Health Data guidelines. Reference Benchimol, Smeeth and Guttmann17
Study design
This retrospective, observational, population-based cohort study was conducted using administrative health data from Alberta between April 1, 2014, and March 31, 2018, with an inclusion period between April 1, 2015, and March 31, 2017; a CM screening period from April 1, 2014, to March 31, 2017; an index date of April 1, 2017; and a 1-year observation period between April 1, 2017, and March 31, 2018.
Data source
Canadian provinces provide publicly funded healthcare for all residents. In Alberta, the fourth most populous province in Canada (4.2–4.3 million people in 2017/2018), healthcare is administered under the Alberta Health Care Insurance Plan (AHCIP), of which over 99% of Albertans participate. 18,Reference Jin, Elleho, Sanderson, Malo, Haan and Odynak19 A person-level data extract from the Discharge Abstract Database (DAD), National Ambulatory Care Reporting System (NACRS), Practitioner Claims, Pharmaceutical Information Network (PIN) and Vital Statistics was linked to the Population Registry using a unique individual identifier (Personal Health Number) and then deidentified and provided to the researchers by the data custodians. DAD and NACRS include demographic, administrative, diagnostic, procedural and resource intensity weight information on people discharged from the hospital (DAD) and ED and facility-based non-emergent ambulatory care clinics (NACRS). Diagnostic fields for each visit include the most responsible diagnosis and room for up to 24 (DAD) and 9 (NACRS) secondary International Classification of Disease Version 10 Canadian Enhancement (ICD-10-CA) codes. Physician visits were obtained from the Practitioner Claims database that include patient, provider and service information such as demographics, physician specialty, date of service, amount paid to the service provider (on fee-for-service, alternative payment plan physician billing and shadow billing) and health service and diagnostic codes; up to ICD – Version 9 – Clinical Modification (ICD-9-CM; Alberta specific) diagnostic codes can be used per visit. The PIN contains information on all dispensed prescription medications from community pharmacies. Vital statistics contains information on all events related to an individual’s entrance and departure from life. The Provincial Registry contains demographic information for all Albertans with AHCIP coverage; elements include migration in and out of the province and birth and death indicators. Variables were checked for inconsistencies; inconsistent data were corrected using information majority or most recent data, where applicable.
Cohort selection
The migraine cohort included those who (1) were aged 18–65 years and had ≥1 hospitalization, ED visit, ambulatory care visit (i.e., facility-based non-emergent ambulatory care clinic visit) or physician visit with a recorded diagnostic code for migraine (ICD-10-CA G43 or ICD-9-CM 346 located in any diagnostic field) during the inclusion period; Reference Widdifield, Ivers and Young20 (2) had AHCIP coverage ≥2 years before the index date and ≥1 year after the index or until death, whichever came first; and (3) were matched with three individuals in the control cohort. Among those within the migraine cohort, the CM group was defined as those who had (1) ≥1 botulinum toxin injection for the prophylaxis of CM (available in Alberta for eligible individuals aged 18–65 years; identified by the Health Service Procedure Code 13.59O) during the inclusion period or (2) had a predicted probability score ≥0.55 from a CM case-finding multivariable logistic regression model during the inclusion period (based on 4 predictors: female vs male sex, ≥24 vs <24 healthcare visits of any type, ≥15 vs <15 acute migraine medication dispensations and 1 or ≥2 vs 0 prophylactic migraine drug class dispensations measured over 1-year increments during the CM screening period). Reference Richer, Wong and Martins21 Individuals in the migraine cohort who did not meet the criteria for the CM group were included in the EM group. Age was restricted to allow for the identification of eligible individuals who received a botulinum toxin injection for the prophylaxis of CM during the inclusion period.
The control cohort was initially selected based on adult residents of Alberta who (1) did not have any healthcare encounters with a recorded diagnosis of migraine during the inclusion period and (2) had AHCIP coverage ≥2 years before the index date and ≥1 year after the index or until death, whichever came first. Individuals who met these criteria were then directly matched at a 3:1 ratio with individuals in the migraine cohort where possible. Exact matching factors included age, sex and residence (urban or rural) on the index date, along with the Charlson Comorbidity Index score that was determined during the 2-year pre-index period. Selection criteria for the control cohort and matching were performed by data custodians and provided to the researchers. The researchers conducted balance diagnostics to ensure that the matched groups were comparable on baseline characteristics, and the effectiveness of matching was assessed by examining standardized mean differences between the migraine and control cohorts post-matching.
Study measures
Baseline characteristics
Demographic characteristics included age, sex and residence (based on the second digit of the postal code) on the index date. Clinical characteristics included the Charlson Comorbidity Index and specific migraine-related comorbidities. A Charlson Comorbidity Index score was determined during the 2-year pre-index period that was based on ICD-10-CA and ICD-9-CM codes of 17 different specific medical conditions weighted according to their potential for influencing mortality (Supplementary Table 1). Reference Charlson, Pompei, Ales and MacKenzie22,Reference Lix, Smith and Pitz23 Migraine-related comorbidities included anxiety, Reference Marrie, Fisk and Yu24 asthma, Reference Tonelli, Wiebe and Fortin25 cardiovascular disease, Reference Tonelli, Wiebe and Fortin25–Reference Tu, Mitiku, Lee, Guo and Tu29 chronic pain, Reference Tonelli, Wiebe and Fortin25,Reference Tian, Zlateva and Anderson30 depression, Reference Doktorchik, Patten and Eastwood31,Reference Alaghehbandan, Macdonald, Barrett, Collins and Chen32 epilepsy, Reference Reid, St Germaine-Smith and Liu33 hypertension Reference Tonelli, Wiebe and Fortin25 and obstructive sleep apnea; Reference Laratta, Tsai, Wick, Pendharkar, Johannson and Ronksley34 each participant was classified with respect to the presence or absence of a condition determined during the 2-year pre-index period (Supplementary Table 2).
Healthcare resource utilization and cost
During the 1-year post-index observation period, all-cause and migraine-related (ICD-10-CA G43 located in the most responsible diagnostic field; ICD-9-CM 346 located in any diagnostic field) healthcare resource utilization and costs were determined for acute care (hospitalizations, ED visits), outpatient care (ambulatory care, physician visits) and community pharmacy dispensed prescription medications (all-cause and acute and prophylactic migraine [Supplementary Table 3]). Note that calcitonin gene-related peptide receptor (CGRP) antagonists were not available in Canada during the study period. Acute and ambulatory care costs were derived by multiplying the associated resource intensity weight with the Canadian Institute for Health Information (CIHI) standardized cost for Alberta in 2017/2018. 35,36 Resource intensity weight is a measure to estimate healthcare resource use and represents the relative value of resources that a given patient, contingent on diagnostic case-mix, would be expected to consume relative to a standard patient; CIHI provides standardized average costs incurred through the direct care of a standardized patient. 35 Physician visit costs were based on the actual amount paid. Drug costs were calculated using the drug product identification number and quantity dispensed, combined with the drug list price (from Alberta Blue Cross); a 3% per unit markup and a $12.15 dispensing fee were included. 37,38 Costs were reported in 2022 $CDN. 39
Medication use
The proportion of those who received ≥1 dispensation for an all-cause and migraine-related (acute and prophylactic [overall and type]) prescription medication was measured during the 1-year post-index observation period. Among those who received ≥1 dispensation (all-cause, migraine-related [acute and prophylactic]), the total number of dispensations was reported.
Statistical analysis
Descriptive statistics were reported as counts and percentages, means with standard deviations (SD) and/or medians with interquartile ranges (IQR), where appropriate. In accordance with data custodian privacy standards, outcomes with 1–9 individuals were reported as <10. To guide multivariable analyses, a conceptual framework was developed using a structural equation modeling-like directed acyclic graph (DAG) that described the role of covariates in the relationship between migraine and healthcare cost (Supplementary Figure 1). Reference Textor, van der Zander, Gilthorpe, Liskiewicz and Ellison40 The DAG suggested a minimal sufficient adjustment set for estimating the total effect of migraine on healthcare costs, including demographic characteristics (age, sex and residence), overall health burden (Charlson Comorbidity Index) and the migraine-related comorbidities of anxiety, asthma, cardiovascular disease, depression, epilepsy, hypertension and obstructive sleep apnea; these confounders were matched and/or adjusted for in the multivariable analyses. One- and two-part generalized linear models (GLM) with a gamma distribution and log link function were employed to examine cost differences. When minimal or absent zero cost values were present, a one-part GLM gamma model was used, producing cost ratios. When cost outcomes had prevalent zero values, a two-part GLM approach was adopted. Reference Duan, Manning, Morris and Newhouse41 The first part involved using logistic regression to predict the odds of observing a nonzero cost (i.e., having a healthcare encounter), yielding the odds ratios of having a nonzero cost. The second part, conditional on a nonzero cost, involved a GLM gamma model to produce the cost ratios and estimate costs. Incremental cost was presented by cost ratios (accompanied by odds ratios in two-part models) and the difference between predicted costs using an average marginal effect approach. 42 Incremental cost represents the additional healthcare costs incurred by the migraine cohort compared with matched controls (and CM vs EM) during the 1-year observation period. The healthcare cost attributable to persons living with migraine in Alberta was estimated by multiplying the per-person per-year incremental cost of the migraine cohort by the estimated prevalence of migraine (8.3%–10.2%) and the 2022 population of Alberta (N = 4,510,891). Reference Graves, Gerber and Berrigan5,18 Analyses were performed using R (v4.2.3; R Core Team 2021) and STATA software (v18; StataCorp LLC, College Station, TX, USA).
Results
Cohort selection
After applying selection criteria and conducting matching, a total of 100,502 were included in the migraine cohort (CM group: n = 47,739; EM group: n = 52,763); 301,506 were in the control cohort (Figure 1; Supplementary Figure 2). The matching rate was high – only 1.6% (n = 1,594) of those that met the criteria for the migraine cohort had <3 matched controls (Figure 1).
Migraine and control cohort selection flow diagram. AHCIP = Alberta Health Care Insurance Plan.
Baseline characteristics
Individuals within the control cohort were exactly matched on age, sex and residence to those in the migraine cohort (Table 1). The Charlson Comorbidity Index scores of the control cohort were not exactly matched to the migraine cohort (standardized mean difference = 0.10); to remove this potential residual confounding bias, the Charlson Comorbidity Index score was used as a covariate in the adjusted cost analysis models. Reference Nguyen, Collins and Spence43
Baseline characteristics
SD = standard deviation.
The average age of the migraine and control cohorts was 43 (SD 14) years, comprised predominately of females (76.8%) and mostly lived in urban areas (86.3%) (Table 1). The CM group (and their matched controls) was more likely to be older (45 [SD 15] vs 41 [SD 14] years of age) and had a higher proportion of females (97.1% vs 58.4%) compared with the EM group (and their matched controls) (Table 1). Persons living with migraine (migraine cohort, CM and EM) were more likely to have a higher proportion of migraine-related comorbidities (anxiety, depression, epilepsy, hypertension, obstructive sleep apnea, chronic pain and cardiovascular disease) compared with matched controls (Table 1). The CM group was more likely to have a larger proportion of migraine-related comorbidities compared with the EM group (Table 1).
Healthcare resource utilization and medication use
The migraine cohort was more likely to have had a higher proportion with ≥1 all-cause hospitalization (9.2% vs 7.4%), ED visit (37.9% vs 24.5%), ambulatory care visit (47.8% vs 33.6%) and physician visit (95.7% vs 84.1%) compared with the matched control cohort during the 1-year post-index observation period; the CM and EM groups were also more likely to have a larger proportion with ≥1 all-cause visit for all healthcare resources compared with matched controls (Table 2). Compared with EM, the CM group was more likely to have a larger proportion with ≥1 all-cause hospitalization (CM vs EM: 13.1% vs 5.7%), ED visit (45.9% vs 30.6%), ambulatory care visit (61.1% vs 35.7%) and physician visit (98.5% vs 93.1%) (Table 2). See Supplementary Table 4 for migraine-related healthcare resource utilization.
All-cause healthcare resource utilization during the 1-year post-index observation period
IQR = interquartile range; SD = standard deviation.
A higher proportion of persons living with migraine were more likely to have had ≥1 dispensation for any medication compared with matched controls (migraine cohort: 91.0% vs 75.5%; CM: 96.2% vs 80.2%; EM: 86.2% vs 71.2%) during the 1-year post-index observation period (Table 3). Overall, 52.3% of the migraine cohort (CM: 62.8%; EM: 42.8%) was dispensed an acute migraine medication (Table 3); the most common (>10%) types were opioids (migraine cohort: 28.4%; CM: 38.5%; EM: 19.3%), nonsteroidal anti-inflammatory drugs (migraine cohort: 22.7%; CM: 28.2%; EM: 17.7%) and triptans (migraine cohort: 22.0%; CM: 25.6%; EM: 18.8%) (Figure 2). During the 1-year post-index observation period, 31.3% of the migraine cohort (CM: 44.7%; EM: 19.2%) received ≥1 dispensation for a prophylactic migraine medication (Table 3). The most common types were antidepressants (migraine cohort: 15.1%; CM: 21.1%; EM: 9.6%) and antiseizure medications (migraine cohort: 12.2%; CM: 19.2%; EM: 5.9%); botulinum toxin (12.1%) and antihypertensives (11.0%) were also common among the CM group (Figure 2).
Types of acute and prophylactic migraine medication used during the 1-year post-index observation period. Less than 0.5% received an ergot (migraine cohort: 0.2%; CM group: 0.3%; EM group: 0.1%; matched control groups: 0.0% each), calcium antagonist (migraine cohort: 0.3%; CM group: 0.4%; EM group: 0.1%; matched control groups: 0.0% each) or antihistamine (migraine cohort: 0.0%; CM group: 0.1%; EM group: 0.0%; matched control groups: 0.0% each). NSAID = nonsteroidal anti-inflammatory drug.
Medication use during the 1-year post-index observation period
Note that calcitonin gene-related peptide (CGRP) inhibitors were not available in Canada during the observation period. IQR = interquartile range; SD = standard deviation.
Healthcare cost of migraine
After matching and adjusting for confounding factors, the fully adjusted total healthcare cost was 1.5 times higher (cost ratio: 1.53 [95% confidence interval [CI]: 1.50, 1.55) in the migraine cohort ($8,126 [95% CI: $7,914, $8,339] per person per year) compared with the matched control cohort ($5,320 [95% CI: $5,197, $5,443] per person per year), with persons living with migraine having a predicted incremental cost of $2,806 (95% CI: $2,664, $2,948) per person per year (Table 4). The total healthcare cost of the CM group was 1.9 times higher (cost ratio: 1.88 [95% CI: 1.84, 1.92]) than matched controls ($10,796 [95% CI: $10,513, $11,078] vs $5,736 [95% CI: $5,602, $5,870] per person per year), with persons living with CM having a predicted incremental cost of $5,059 (95% CI: $4,836, $5,283) per person per year (Table 4). The total healthcare cost of the EM group was 1.1 times higher (cost ratio: 1.14 [95% CI: 1.11, 1.18]) than matched controls ($5,394 [95% CI: $5,112, $5,676] vs $4,725 [95% CI: $4,507, $4,943] per person per year), with persons living with EM having a predicted incremental cost of $669 (95% CI: $512, $827) per person per year (Table 4). The full multivariable regression model is shown in Supplementary Table 5. Similar patterns were observed in sensitivity analysis that did not adjust for migraine-related comorbidities, with an increased effect size; for example, the incremental cost of persons living with CM was $6,644 (95% CI: $6,358, $6,930) compared with $5,059 (Supplementary Table 6). Hospitalization, ED, ambulatory care, physician and prescription drug costs all significantly contributed to the higher cost of persons living with migraine (migraine cohort, CM and EM [with the exception of hospitalization for EM]); prescription drugs were the primary cost driver, especially for the CM group (Table 5).
Total healthcare cost comparisons between those living with migraine and matched controls, and between chronic and episodic migraine, measured during the 1-year post-index observation period
Estimated by one-part generalized linear model with log link and gamma distribution. Individuals in the control cohort were exactly matched with individuals in the migraine cohort on age, sex and urban/rural residence; the Charlson Comorbidity Index was not exactly matched and therefore further adjusted in the cost analysis model. Adjustments for the migraine-related comorbidities of anxiety, asthma, depression, epilepsy, cardiovascular disease, hypertension and obstructive sleep apnea were included. CDN = Canadian; CI = confidence interval.
Comparison of healthcare cost components between those living with migraine and matched controls and between chronic and episodic migraine, measured during the 1-year post-index observation period
Estimated by two-part gamma hurdle models (hospitalizations, emergency department visits and ambulatory care visits) or a one-part generalized linear model with log link and gamma distribution (physician visits and outpatient medication) and matched on or adjusted for age, sex, residence, Charlson Comorbidity Index score and the migraine-related comorbidities of anxiety, asthma, depression, epilepsy, cardiovascular disease, hypertension and obstructive sleep apnea. CI = confidence interval, NA = not applicable (for the one-part model).
After adjusting for confounding factors (age, sex, residence, overall health burden [Charlson Comorbidity Index] and migraine-related comorbidities), the total healthcare cost was higher (all-cause cost ratio: 2.25 [95% CI: 2.19, 2.31]; migraine-related cost ratio: 4.10 [95% CI: 3.97, 4.24]) in the CM group (all-cause: $8,367 [95% CI: $8,207, $8,526]; migraine-related: $870 [95% CI: $852, $888]) compared with the EM group (all-cause: $3,721 [95% CI: $3,638, $3,804]; migraine-related: $212 [95% CI: $207, $217]); the CM group had a predicted all-cause incremental cost of $4,646 (95% CI: $4,478, $4,813) and migraine-related incremental cost of $658 (95% CI: $639, $677) per person per year versus the EM group (Table 4).
Discussion
In this retrospective, observational, population-based cohort study of adults living with and without migraine in Alberta, the incremental direct healthcare cost of persons living with migraine (overall, CM and EM) and cost by migraine classification between CM and EM was determined between April 1, 2017, and March 31, 2018, using administrative health data (reported in 2022 $CDN). After adjusting for confounders, the annual total mean healthcare cost of persons living with migraine was 1.5 times higher than matched controls, with a predicted incremental cost of $2,806 per person per year; the CM group was 1.9 times higher, and the EM group was 1.1 times higher than respective matched controls. While all healthcare cost categories contributed to the higher cost of persons living with migraine (overall, CM and EM), prescription medication was the primary cost driver. The cost of the CM group was 2.3 times higher than the EM group, with a predicted incremental cost of $4,646 per person per year. Findings show that persons living with migraine had greater direct healthcare costs than those without, particularly for those living with CM, which persisted after matching and adjustment for confounders, including comorbid conditions commonly observed in persons living with migraine.
Previous studies indicate that persons living with migraine have higher healthcare costs compared with those not living with migraine. Reference Wolfson, Fereshtehnejad, Pasquet, Postuma and Keezer8–Reference Gilligan, Foster, Sainski-Nguyen, Sedgley, Smith and Morrow11 Findings from a large commercial administrative claims database in the USA (Truven Health MarketScan; covers approximately 38 million employees and their dependents) showed that adults living with migraine had a higher total all-cause mean annual direct healthcare cost compared with propensity score matched individuals who were not living with migraine ($13,032 [95% CI: $12,919, $13,144] vs $3,234 [95% CI: $3,202, $3,266] per person; 2016 $USD). Reference Gilligan, Foster, Sainski-Nguyen, Sedgley, Smith and Morrow11 Relatively few studies have been conducted on the healthcare cost of persons living with migraine in Canada. Reference Stokes, Becker and Lipton13–Reference Graves, Cowling and McMullen16 McMullen et al. (2023) and Graves et al. (2023) described the total direct healthcare cost of a retrospective population-based cohort living with incident (newly diagnosed/recurrent) migraine among adults between 2012 and 2018 using administrative data from Alberta. Reference McMullen, Graves, Ekwaru, Pham, Mayer, Ladouceur, Hubert, Bougie and Amoozegar15,Reference Graves, Cowling and McMullen16 During a follow-up period after the incident date, the total all-cause mean annual direct healthcare cost was $6,403 (SD $39,880) for persons living with migraine, $12,693 (SD $40,644) for CM and $4,251 (SD $40,637) for EM per person (2020 $CDN). Reference McMullen, Graves, Ekwaru, Pham, Mayer, Ladouceur, Hubert, Bougie and Amoozegar15,Reference Graves, Cowling and McMullen16 Results of the current study extend findings by reporting the annual incremental all-cause direct healthcare cost of adults living with migraine ($2,806), including CM ($5,059) and EM ($669) per person, compared with matched controls. With an estimated migraine prevalence of 8.3%–10.2%, this condition may account for an additional $1.05–1.29 billion in healthcare costs per year in Alberta.
Among the different types of migraine, individuals living with CM consistently display higher healthcare resource use and costs compared with those living with EM. Reference Messali, Sanderson and Blumenfeld12–Reference McMullen, Graves, Ekwaru, Pham, Mayer, Ladouceur, Hubert, Bougie and Amoozegar15 Based on survey responses from Canadian participants of the International Burden of Migraine Study (n = 679), those living with CM reported higher healthcare resource use and had a total direct healthcare cost that was 2.7 times higher than EM as determined during a 3-month period. Reference Stokes, Becker and Lipton13 McMullen et al. (2023) described higher rates of healthcare use and an average annual total direct healthcare cost that was 3.0 times higher for those living with CM compared with EM in Alberta. Reference McMullen, Graves, Ekwaru, Pham, Mayer, Ladouceur, Hubert, Bougie and Amoozegar15 Collectively, findings from previous reports and the current study help elucidate the economic burden associated with CM and EM; this has implications for guiding treatment decisions and the management of persons living with migraine. To this end, opioids were the most common migraine-related drug used by persons living with migraine in this study, particularly CM; higher use of opioids has been shown to be associated with higher healthcare use and costs among persons living with migraine. Reference Bonafede, Cai and Cappell44 While opioids may be helpful in some persons living with migraine, routine use is not recommended as it increases the propensity of developing medication-overuse headache, the risk of developing new-onset CM and the likelihood of becoming more refractory to other acute migraine medications and may lead to misuse or abuse resulting in dependence. Reference Becker45–Reference Shao, Rascati, Lawson, Barner, Sonawane and Rousseau49 Providing care management and effective treatments for migraine that result in reduced opioid use may represent a potentially modifiable factor that could facilitate a reduction in healthcare costs and an improvement in quality of life for those living with migraine.
The period over which this study was conducted occurred before CGRP antagonists were available in Canada. This new class of drug for the prophylactic treatment of CM and EM has a favorable safety and tolerability profile and displays promising efficacy in a significant number of persons living with migraine. Reference Ford, Foster, Stauffer, Ruff, Aurora and Versijpt50–Reference Vernieri, Altamura and Brunelli53 However, these drugs are costly. Considering that prescription medication was the primary direct healthcare cost driver of persons living with migraine in this study, the use of CGRP antagonists may additionally increase this cost category if widely used. Therefore, the rationale use of this new drug class will need to consider possible reductions in other healthcare cost categories and the benefits in quality of life that may be realized, as well as the societal cost of migraine. To this end, CGRP antagonists have shown improved quality of life and productivity and reduced the number of monthly migraine days and the use of acute migraine medication in persons living with migraine. Reference Ford, Foster, Stauffer, Ruff, Aurora and Versijpt50–Reference Vernieri, Altamura and Brunelli53 Health economic and cost-effectiveness models have shown that treatment with CGRP antagonists has the potential to reduce both direct healthcare costs and the societal burden of migraine. Reference Pozo-Rosich, Poveda, Crespo, Martinez, Rodriguez and Irimia54–Reference Siersbaek, Kilsdal, Jervelund, Antic and Bendtsen56 This is important as direct non-healthcare costs (e.g., transportation for medical appointments, childcare costs) and indirect costs (e.g., productivity loss) may account for the majority (52%–64%) of the overall economic burden of migraine in Canada; Reference Amoozegar, Khan, Oviedo-Ovando, Sauriol and Rochdi14 indirect costs have been reported to account for 87% of the annual cost of migraine in Canada among those living with moderate-to-severe migraine. Reference Lambert, Carides, Meloche, Gerth and Marentette57
Important strengths of this study are the large population-based design, high-quality source of administrative health data that contains information on comprehensive healthcare resources in Alberta and analytical approach (multivariable analyses guided by a pre-defined conceptual framework). However, this study is also subject to several limitations that should be taken into consideration when interpreting results. Retrospective administrative claims-based studies use administrative data as opposed to medical records, and therefore, there is a potential for misclassification of the study groups or measures. Previously detailed, although migraine diagnostic codes from administrative claims data have been shown to reliably detect migraine status, this strategy may have missed a large number of persons living with migraine in the population, as many persons living with migraine either do not seek medical care for their condition or are not properly diagnosed. Reference Richer, Wong and Martins21 As a validated case-finding algorithm was not available at the time of this study for the identification of individuals living with CM using Canadian administrative data, adaptation of a case definition from the USA was used. Reference Pavlovic, Yu and Silberstein58 This case definition does preferentially include females. While receipt of ≥1 botulinum toxin injection for the prophylaxis of CM was an inclusion criterion for the CM group, some individuals living with CM who respond to botulinum toxin treatment will convert to EM. Reference Andreou, Trimboli and Al-Kaisy59,Reference Ahmed, Buture, Tanvir and Khalil60 Therefore, the misclassification of some individuals within the CM and EM groups may have occurred. The PIN database only provides information on prescription medication dispensations (over-the-counter medications excluded) from community pharmacies and may not represent actual medication uptake by individuals. This study was conducted from the perspective of the Canadian healthcare system and did not include costs borne by individuals or indirect costs. Previous studies have shown that when a societal perspective is considered, costs outside the healthcare system account for the majority of the economic burden of migraine in Canada. Reference Amoozegar, Khan, Oviedo-Ovando, Sauriol and Rochdi14,Reference Lambert, Carides, Meloche, Gerth and Marentette57
Conclusions
This study provides insights into the direct healthcare costs associated with persons living with migraine, including CM and EM in Alberta. Adults living with migraine, particularly those living with CM, used greater healthcare resources and incurred higher incremental costs compared with those not living with migraine that was primarily driven by prescription medication cost. Findings from this study support the rationale for strategies to prevent and effectively manage migraine that reduce associated healthcare and societal costs, along with improving the quality of life for persons living with migraine.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/cjn.2025.40.
Data availability statement
The data that support the findings of this study are available from Alberta Health Services and Alberta Health, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
Acknowledgments
We thank the participants of this study. This study is based in part on anonymized raw data from Alberta Health and Alberta Health Services, which was provided by the Alberta Strategy for Patient-Oriented Research Unit housed within Alberta Health Services. The interpretation and conclusions contained herein are those of the researchers and do not necessarily represent the views or opinions of the Government of Alberta or Alberta Health Services. Scott Klarenbach was supported by the Kidney Health Research Chair and the Division of Nephrology at the University of Alberta.
Author contributions
KV, HL, KM and SK contributed to the study concept and design. PUN, HL and KV conducted the analyses. HS and PUN created the tables and figures, and HS and KM prepared the draft manuscript. All authors contributed to the interpretation of the data and critical revision of the report for intellectual content. SK provided study supervision.
Funding statement
Funding was not received for this research study.
Competing interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this manuscript: PUN, HL, HS, KV, KM, LR, TW and SK are members of the Alberta Real World Evidence Consortium (ARWEC) and the Alberta Drug and Therapeutic Evaluation Consortium (ADTEC); these entities (comprised of individuals from the University of Alberta, University of Calgary and Institutes of Health Economics) conduct research including investigator-initiated industry-funded studies (ARWEC) and government-funded studies (ADTEC). WB reports receiving consulting fees from Allergan/AbbVie, Linpharma, Novartis, Lundbeck, Eli Lilly, Teva, Pfizer and McKesson; honoraria from Allergan/AbbVie, Novartis, Weber and Weber, Lundbeck and Teva. FA reports receiving research support from Eli Lilly, Allergan/AbbVie, Biohaven, Novartis, Teva and Lundbeck; consulting fees from Eli Lilly, Novartis, Teva, Lundbeck, ICEBM and Pfizer; and speaker honoraria from Eli Lilly, Novartis, Teva, Allergan/Abbie, ICEBM and Aralez. LR reports receiving research support from Allergan/AbbVie. All authors of this study had complete autonomy over the content and submission of the manuscript, as well as the design and execution of the study.
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