Abstract
Background
Migraine is a prevalent and disabling condition affecting one billion people worldwide. calcitonin gene-related peptide (CGRP) inhibitors have transformed migraine management. We describe real-world trends in CGRP inhibitor treatment, switching, discontinuation, and migraine-related health care use (including emergency department, ED, and ambulatory care visits).
Methods
We used the Merative™ MarketScan® Research data, providing data on inpatient and outpatient healthcare use and drug dispensation from a large sample of individuals with employer-sponsored health insurance in the United States. We identified adults using CGRP inhibitors (comprising both monoclonal antibodies, mAbs, and small-molecule CGRP receptor antagonists, gepants) as preventive treatment for migraine between May 2018 and December 2022. We evaluated treatment patterns, including switching between CGRP agents or other prophylactic migraine treatments, and therapy discontinuation. Healthcare and migraine-related medication use were compared one year pre- and post-CGRP inhibitor initiation. Migraine-related medications included preventive migraine-specific treatments (e.g., onabotulinumtoxinA), non-specific preventives (e.g., antidepressants), and acute treatments—both migraine-specific (e.g., triptans) and non-specific (e.g., opioids).
Results
We studied 148,100 adults with at least one CGRP inhibitor dispensation. CGRP inhibitor use increased over time, with newer agents being more commonly dispensed in recent years. Within the first year, 10.3% of individuals switched between CGRP inhibitors, and an additional 13.5% discontinued their first CGRP inhibitor without switching to another. Post-initiation, there was a 4.5% reduction in migraine-related medication use (95% confidence interval, CI: -4.9% to -4.0%, and 12.8% reduction in healthcare use (95% CI: -13.2% to -12.3%).
Conclusions
CGRP inhibitors are increasingly used over time. About 10% switch between CGRP agents within the first year of initiation. There was reduction in other migraine-related medications and healthcare visits following CGRP initiation.
Trial registration
N/A.
Supplementary Information
The online version contains supplementary material available at 10.1186/s10194-025-02167-0.
Keywords: Migraine, Calcitonin gene-related peptide inhibitors, Treatment patterns, Administrative data
Background
Migraine is a highly prevalent and disabling neurological disorder affecting 1 billion people worldwide, representing the second most common disease globally [1, 2]. About 15% of adults in North America experience migraine, affecting 42 million individuals in the United States (US) and Canada [3–6]. Migraine thus imposes substantial economic costs on individuals, healthcare systems, and society. In the US alone, migraine-related healthcare expenses (drugs, physician and emergency department [ED] visits) exceed $36 billion annually [7].
The treatment of migraine typically involves both acute treatments and preventive (prophylactic) therapies [8, 9]. Acute treatments like triptans and ergot derivatives have traditionally been used, along with non-specific medications such as non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, etc. In recent years, calcitonin gene-related peptide (CGRP) inhibitors have transformed acute and preventive migraine management, providing a novel mechanism of action [10]. CGRP inhibitors include monoclonal antibodies (mAbs) such as erenumab, fremanezumab, galcanezumab, and eptinezumab (preventives), as well as small-molecule CGRP receptor antagonists, known as gepants (e.g., rimegepant and atogepant), which can be used as acute and/or preventives depending on the specific agent. Trials have demonstrated fewer adverse effects with CGRP inhibitors compared to traditional options, translating to better tolerability and adherence rates [11, 12]. Both the American and Canadian Headache Societies have recognized CGRP inhibitors as a first-line option for migraine prevention, particularly for frequent and debilitating attacks [13, 14].
Despite the promise of CGRP inhibitors, their high cost necessitates careful formulary consideration of policies governing access. In Canada, access to CGRP inhibitors is limited to patients with at least 4 monthly migraine days and documented failure with at least two prior preventive therapies [15, 16]. Similarly, in the US, most managed care organizations require at least two or three previous attempts with alternative medications before providing access to CGRP inhibitors [17].
To ensure that public spending is focused on individuals living with migraine who benefit from these drugs, tracking treatment persistence and adherence in the real world is critical to identifying this population [18]. We aimed to describe real-world trends in the use of CGRP inhibitors, including treatment patterns, switching, discontinuation, and association with healthcare resource use. This study was conducted in response to the needs of real-world policy makers and funded by the Post-Market Drug Evaluation program within Canada’s Drug Agency [19].
Methods
Design and data source
We conducted a retrospective cohort study using the US Merative™ MarketScan® Research Database, which includes de-identified patient-level claims data on in-hospital and outpatient resource use from various health insurance providers in the US. Our focus was on the Commercial Claims and Encounters database, encompassing employer-sponsored private health insurance records for employees, their spouses, and dependents, and Medicare supplemental insurance for retirees [20]. The database complies with the Health Insurance Portability and Accountability Act (HIPAA) to ensure patient privacy.
Population
The study included adult individuals (≥ 18 years) with at least one new claim of a CGRP inhibitor for migraine prevention, either a mAb (galcanezumab, eptinezumab, fremanezumab, or erenumab) or a gepant (atogepant, rimegepant) between May 17, 2018, and December 31, 2022. Rimegepant dispensations were included only if issued after May 2021 and indicated a supply of 30 days or more. This threshold was chosen to distinguish preventive use (often involving every other day dosing) from acute, needs-based dosing [21]. The date of the first qualifying claim was the index date. CGRP inhibitors were identified using National Drug Code (NDC) codes on pharmacy claims and Healthcare Common Procedure Coding System (HSPCS) codes on medical claims (Supplemental Table 1).
Baseline characteristics and medication use during the first year were described for CGRP users that had continuous medical and pharmacy coverage for at least one year before and after the index date. For subgroups describing CGRP utilization over fixed yearly follow-ups, individuals needed continuous coverage for one-, two-, three-, or four-years post-index.
Study variables
Trends in CGRP inhibitor prevalence (by 100,000 enrollees) from 2018 to 2022 were described based on individuals with at least one dispensation each year. Treatment patterns were assessed over fixed follow-up durations, including one-, two-, three-, and four-years post-initiation. Treatment periods of CGRP inhibitors, onabotulinumtoxinA, and other non-migraine-specific prophylactic medications (Supplemental Table 2) were identified. Each dispensation or claim was considered to last for the duration of the days’ supply, or 90 days in the case of eptinezumab infusions or onabotulinumtoxinA injections. Overlaps of ≤ 30 days between dispensations of the same medication were treated as early refills, with the end date of the subsequent dispensation adjusted to account for overlapping days. Early claims for eptinezumab and onabotulinumtoxinA were not adjusted.
A new treatment period, whether with a different CGRP inhibitor, onabotulinumtoxinA, or a non-migraine-specific prophylactic medication, was classified as a switch if the prior CGRP treatment period had ended with no additional dispensation or claim after the start of the new treatment. An overlap of ≤ 30 consecutive days between the prior and new treatment was allowed. Switching events were mutually exclusive and prioritized as follows: (i) CGRP; (ii) onabotulinumtoxinA; and (iii) other non-migraine-specific prophylaxis. Concomitant use events (overlapping of ≥ 30 days between dispenses) were classified as: (i) CGRP with onabotulinumtoxinA, with or without other non-migraine-specific prophylaxis; (ii) CGRP with other non-migraine-specific prophylaxis. A treatment break was defined as a gap of > 120 days from the end of the previous period followed by resumption of the same treatment. Discontinuation was recorded when the current CGRP treatment ended without a subsequent switch or resumption.
Baseline characteristics, medication use, and healthcare resource use were described for CGRP users meeting the coverage criteria. Characteristics included age, sex, residence (urban vs. rural), Charlson Comorbidity Index [22] (Supplemental Table 3) and relevant comorbidities, such as cardiovascular disease, depression, anxiety, asthma, epilepsy, hypertension, and obstructive sleep apnea (Supplemental Table 4).
Characteristics assessed for the one-year intervals before and after the index date included:
Use of migraine-related medications, including acute and prophylactic therapies.
Migraine-related healthcare encounters, including hospitalizations, ED visits, ambulatory care, and outpatient physician visits (Supplemental Table 5).
Statistical analysis
All individuals who met the inclusion criteria were included in the analysis. No observations were excluded. Outliers or other data points were not removed based on pre-defined criteria. The number of CGRP users was reported for each year from 2018 to 2022, with the proportion calculated per 100,000 insured individuals. The analysis was stratified by age group (18–44, 45–64, and 65+) and sex.
For treatment patterns with fixed follow-up durations, the number and proportions of switching, concomitant use, treatment break, and discontinuation were reported for the first, second, third, and fourth years. The denominator was the number of people who had health coverage for at least one, two, three, or four years post-index date. Treatment trajectories in the first year were depicted using a Sankey diagram.
Kaplan-Meier methods estimated the cumulative probability of first: (i) discontinuation, (ii) switch, or (iii) treatment break. Individuals were followed from CGRP inhibitor initiation until the event of interest, loss to follow-up (i.e., insurance plan disenrollment), or study period’s end, whichever occurred first.
Baseline characteristics were summarized as means (with standard deviations, SD) and medians (with first and third quartiles, Q1-Q3) for continuous variables, and as counts and percentages for categorical variables.
Migraine-related medication use, and healthcare encounters were described as frequencies and proportions for the one-year intervals before and after the index date. For medications, the average number of days supply (mean with SD and median with Q1-Q3) was also calculated. For healthcare encounters, the number of visits overall, and by type of encounter, the proportion of individuals with at least one visit, and the length of hospital stay were described using means and medians. Differences in proportions of migraine-related medication use and healthcare encounters between the post- and pre- intervals were calculated, along with their 95% confidence intervals (95% CI).
We conducted subgroup analyses limited to users of mAbs to account for potential differences in treatment patterns and clinical use compared to gepants. Individuals were classified as mAb users if they received at least one dispensation for erenumab, fremanezumab, or galcanezumab during the study period.
Results
We studied 148,100 unique individuals with at least one dispensation of CGRP inhibitor between 2018 and 2022, including 117,884 people initiating mAB medication in the same period. CGRP inhibitor users were predominantly female (85.9%) with a mean age of 43.1 (SD: 12.3) years. The median enrollment duration was 403 days (Q1-Q3: 185–795). Baseline characteristics of CGRP inhibitor users subgroup with continuous medical and pharmacy coverage for at least one year before and after the index date are presented in Supplemental Table 6.
The prevalence of CGRP inhibitor use increased substantially from 2018 to 2022 (Table 1). In 2022, the prevalence of users (per 100,000 enrollees) was almost 10 times higher than that observed in 2018 (the first year CGRP inhibitors became available). The highest use was observed among females and individuals aged 45–64 years, the demographics most characteristic of those with migraine. In 2018, among the three CGRP inhibitors available in the US market at that time, erenumab was dispensed the most. In more recent years, the most dispensed CGRP inhibitors were rimegepant and galcanezumab.
Table 1.
Frequency of calcitonin gene-related peptide (CGRP) inhibitors use, MarketScan, US, 2018–2022
| Calendar year | |||||
|---|---|---|---|---|---|
| 2018 | 2019 | 2020 | 2021 | 2022 | |
| All CGRP, n (rate per 100,000 enrollees) | |||||
| Overall | 10,316 (46.9) | 38,299 (187.2) | 53,377 (278.0) | 69,440 (364.4) | 82,624 (442.3) |
| By age | |||||
| 18–44 | 4,638 (39.1) | 18,578 (166.5) | 26,048 (256.2) | 34,512 (337.9) | 40,895 (411.7) |
| 45–64 | 5,383 (60.3) | 18,936 (229.5) | 26,064 (342.8) | 33,429 (453.3) | 39,400 (558.6) |
| 65+ | 295 (24.3) | 785 (74.4) | 1,265 (88.5) | 1,499 (102.4) | 2,329 (137.4) |
| By sex | |||||
| Female | 8,826 (77.0) | 32,772 (307.2) | 45,916 (459.0) | 59,932 (604.1) | 71,360 (730.6) |
| Male | 1,490 (14.2) | 5,527 (56.5) | 7,461 (81.1) | 9,508 (104.1) | 11,264 (126.4) |
| mAB* | |||||
| Overall | 10,316 (46.9) | 38,299 (187.2) | 53,377 (278.0) | 58,206 (305.5) | 52,761 (282.4) |
| By age | |||||
| 18–44 | 4,638 (39.1) | 18,578 (166.5) | 26,048 (256.2) | 28,456 (278.6) | 25,258 (254.3) |
| 45–64 | 5,383 (60.3) | 18,936 (229.5) | 26,064 (342.8) | 28,435 (385.6) | 25,802 (365.8) |
| 65+ | 295 (24.3) | 785 (74.4) | 1,265 (88.5) | 1,315 (89.8) | 1,701 (100.3) |
| By sex | |||||
| Female | 8,826 (77.0) | 32,772 (307.2) | 45,916 (459.0) | 50,053 (504.5) | 45,345 (464.3) |
| Male | 1,490 (14.2) | 5,527 (56.4) | 7,461 (81.1) | 8,153 (89.3) | 7,416 (83.2) |
| By agent, n (% of CGRP users) | |||||
| Erenumab | 7,918 (76.8) | 16,057 (42.0) | 22,674 (42.5) | 23,024 (33.2) | 15,449 (18.7) |
| Galcanezumab | 998 (9.7) | 13,966 (36.5) | 21,274 (39.9) | 23,320 (33.6) | 23,338 (28.3) |
| Fremanezumab | 1,400 (13.6) | 8,276 (21.6) | 9,321(17.5) | 11,210 (16.1) | 13,056 (15.8) |
| Eptinezumab | 0 (0) | 0 (0) | 108 (0.2) | 652 (0.9) | 918 (1.1) |
| Atogepant | 0 (0) | 0 (0) | 0 (0) | 216 (0.3) | 6,427 (7.8) |
| Rimegepant** | 0 (0) | 0 (0) | 0 (0) | 11,018 (15.9) | 23,436 (28.4) |
Abbreviations: CGRP Calcitonin Gene-Related Peptide, mAB monoclonal antibodies
*Includes erenumab, fremanezumab, galcanezumab, and eptinezumab
**Individuals on rimegepant were included as of May 27, 2021 onwards and only for dispenses with 30 or more days’ supply
Treatment patterns of CGRP inhibitor users considering fixed follow-up duration are described in Table 2. In the initial year of follow-up, 33.7% of the 73,258 initiators remained on their initial CGRP inhibitor and 10.3% switched to a different CGRP inhibitor. By the end of the four-year follow-up, 35.2% of the 3,477 initiators still being followed had switched to a different CGRP inhibitor. Among the CGRP inhibitor initiators, 10.2% switched to onabotulinumtoxinA injections in the first year, and 30.4% switched to another type of migraine prophylaxis. In the first year, 5.1% of CGRP inhibitor users concomitantly used onabotulinumtoxinA injections, while 13.7% used non-migraine-specific prophylactic medication. A treatment break of ≥ 120 consecutive days (without any CGRP inhibitor or other migraine prophylaxis) followed by resumption of the initial CGRP occurred in 1.8% of individuals in the first year. Complete discontinuation of CGRP treatment (i.e. with no resumption) occurred in 13.5% during the first year. Treatment trajectories (Fig. 1) indicate that a small portion of CGRP inhibitor users switched to a second CGRP during the first year, especially when compared to other treatment events such as switching to a non-CGRP prophylactic or discontinuing treatment altogether. Additional details of treatment patterns of individual CGRP inhibitors in the first year of follow-up are provided in Supplemental Table 7.
Table 2.
Treatment patterns of calcitonin gene-related peptide (CGRP) inhibitorusers across 1-, 2-, 3-, and 4-year fixed follow-up, MarketScan, US, 2018–2022
| Follow-up year | ||||
|---|---|---|---|---|
| Initial year | Over 2-year follow-up | Over 3-year follow-up | Over 4-year follow-up | |
| All CGRP | ||||
| N= | 73,258 | 38,385 | 17,263 | 3,477 |
| Remaining on the initial CGRP inhibitor, n (%) | 24,790 (33.7) | 8,057 (21.0) | 2,158 (12.5) | 119 (3.4) |
| Switching from an initial to a subsequent CGRP inhibitor, n (%) | 7,537 (10.3) | 6,077 (15.8) | 3,668 (21.3) | 1,224 (35.2) |
| Switching from a CGRP inhibitor to onabotulinumtoxinA injection, n (%) | 7,483 (10.2) | 4,645 (12.1) | 2,344 (13.6) | 568 (16.3) |
| Switching from a CGRP inhibitor to non-specific migraine prophylactic treatment, n (%) | 22,281 (30.4) | 11,983 (31.2) | 5,183 (30.0) | 843 (24.3) |
| Concomitant CGRP inhibitor treatment and onabotulinumtoxinA injection, n (%) | 3,741 (5.1) | 3,239 (8.4) | 2,017 (11.7) | 676 (19.4) |
| Concomitant use of CGRP inhibitor and non-migraine-specific prophylactic treatment, n (%) | 10,069 (13.7) | 6,802 (17.7) | 3,466 (20.1) | 783 (22.5) |
| Treatment break, n (%) | 1,301 (1.8) | 2,381 (6.2) | 1,939 (11.2) | 508 (14.5) |
| Discontinuation, n (%) | 9,866 (13.5) | 5,242 (13.7) | 1,971 (11.4) | 215 (6.2) |
| mAB* | ||||
| N= | 66,538 | 38,385 | 17,263 | 3,477 |
| Remaining on the initial mAB, n (%) | 22,098 (33.2) | 6,497 (16.9) | 2,158 (12.5) | 119 (3.4) |
| Switching from an initial to a subsequent mAB, n (%) | 6,784 (10.2) | 6,077 (15.8) | 3,668 (21.2) | 1,224 (35.2) |
| Switching from a mAB to onabotulinumtoxinA injection, n (%) | 6,644 (10.0) | 4,645 (12.1) | 2,344 (13.6) | 568 (16.3) |
| Switching from a mAB to non-specific migraine prophylactic treatment, n (%) | 20,516 (30.8) | 11,983 (31.2) | 5,183 (30.0) | 843 (24.2) |
| Concomitant mAB treatment and onabotulinumtoxinA injection, n (%) | 3,346 (5.0) | 3,239 (8.4) | 2,017 (11.7) | 676 (19.4) |
| Concomitant use of mAB and non-migraine-specific prophylactic treatment, n (%) | 9,493 (14.3) | 6,802 (17.7) | 3,466 (20.1) | 783 (22.5) |
| Treatment break, n (%) | 1,003 (1.5) | 2,381 (6.2) | 1,939 (11.2) | 508 (14.6) |
| Discontinuation, n (%) | 8,383 (12.6) | 5,242 (13.7) | 1,971 (11.4) | 215 (6.2) |
Abbreviations: CGRP Calcitonin Gene-Related Peptide, mAB monoclonal antibodies
*Includes erenumab, fremanezumab, galcanezumab, and eptinezumab
Fig. 1.
Treatment trajectories in the first year of follow-up for individual CGRP inhibitors, MarketScan, US, 2018 – 2022
When considering varying follow-up durations, the proportion of those switching from an initial CGRP inhibitor to a subsequent CGRP inhibitor in the first year was 11.3% (95% CI: 11.1%−11.5%) and increased to 16.8% (95% CI: 16.6%−17.1%) in the second year (Supplemental Table 8). The median time to these events, as well as for switching to onabotulinumtoxinA injections and treatment breaks could not be estimated due to a high censoring rate or insufficient events. The probability of discontinuation in the first and second years was 15.7% (95% CI: 15.4%−15.9%) and 29.3% (95% CI: 29.0%–29.7%), respectively, with a median time to first discontinuation of 1,575 days (4.3 years).
Overall, the dispensation of migraine-related medications (both acute and preventive) among CGRP inhibitor users tended to be lower in the one-year post-index when compared to the one-year pre-index interval (Table 3). For example, the proportion of individuals with at least one dispensation of any migraine-related medication decreased from 93.2% in the pre-index interval to 88.7% in the post-index interval (difference: −4.5%, 95% CI: −4.9% to −4.0%). A similar trend was observed for acute medication dispensations, including both non-specific (e.g., NSAIDs) and migraine-specific medications (e.g., triptans), and prophylactic medications, including onabotulinumtoxinA and non-specific treatment (e.g., antidepressants). A few exceptions in this trend were observed in medications within these classes, particularly gepants, which increased in the post-index interval (9.4% pre vs. 12.5% post; difference: 3.1%, 95% CI: 2.8% to 3.4%).
Table 3.
Migraine-related medication use pre- and post-index among calcitonin gene-related peptide (CGRP) inhibitor users, MarketScan, US, 2018–2022
| CGRP inhibitor users n = 55,212 | mAB* users n = 48,834 | |||||
|---|---|---|---|---|---|---|
| One-year Pre-index date† | One-year Post-index date† | Difference (95% CI) |
One-year Pre-index date†† | One-year Post-index date†† | Difference (95% CI) |
|
| Any migraine-related medication | ||||||
| Had ≥ 1 dispensation, n (%) | 51,435 (93.2) | 48,992 (88.7) | −4.5 (−4.9;−4.0) | 45,672 (93.5) | 43,978 (90.1) | −3.5 (−3.8;−3.2) |
| Acute medications, overall | ||||||
| Had ≥ 1 dispensation, n (%) | 47,614 (86.2) | 44,232 (80.1) | −6.1 (−6.5;−5.7) | 42,227 (86.5) | 40,095 (82.1) | −4.4 (−4.7;−4.0) |
| Number of days supplied | ||||||
| Mean (SD) | 162.5 (168.7) | 159.0 (171.3) | 165.6 (170.1) | 163.9 (172.8) | ||
| Median (Q1-Q3) | 101 (35–240) | 94 (30–240) | 105.0 (35.0–249.0) | 100.0 (32.0–245.0) | ||
| Non-specific acute medications | ||||||
| Had ≥ 1 dispensation, n (%) | 30,772 (55.7) | 28,970 (52.5) | −3.2 (−3.8;−2.6) | 27,869 (57.1) | 26,276 (53.8) | −3.3 (−3.8;−2.8) |
| By class, n (%) | ||||||
| NSAIDs | 17,153 (31.1) | 15,467 (28.0) | −3.1 (−3.5;−2.6) | 15,576 (31.9) | 14,098 (28.9) | −3.0 (−3.5;−2.6) |
| Opioids | 13,619 (24.7) | 13,503 (24.5) | −0.2 (−0.6;0.2) | 12,293 (25.2) | 12,178 (24.9) | −0.2 (−0.7;0.2) |
| Migraine-specific acute medications | ||||||
| Had ≥ 1 dispensation, n (%) | 37,223 (67.4) | 32,435 (58.8) | −8.6 (−9.2;−8.0) | 32,682 (66.9) | 27,064 (55.4) | −5.9 (−6.3;−5.4) |
| By class, n (%) | ||||||
| Triptans | 31,717 (57.4) | 25,165 (45.6) | −11.9 (−12.3;−11.5) | 30,099 (61.6) | 24,000 (49.1) | −12.5 (−12.9;−12.1) |
| Ergots | 292 (0.5) | 262 (0.5) | −0.1 (−0.1;0.0) | 289 (0.6) | 250 (0.5) | −0.1 (−0.2;0.0) |
| Ditans | 31 (0.1) | 124 (0.2) | 0.2 (0.1;0.2) | 23 (0.0) | 105 (0.2) | 0.2 (0.1;0.2) |
| Gepants | 5,183 (9.4) | 6,884 (12.5) | 3.1 (2.8;3.4) | 2,271 (4.7) | 5,466 (11.2) | 6.5 (6.3;6.8) |
| Prophylactic medications, overall | ||||||
| Had ≥ 1 dispensation, n (%) | 34,313 (62.2) | 30,151 (54.6) | −7.6 (−7.0;−8.2) | 31,059 (63.6) | 27,064 (55.4) | −8.2 (−8.6;−7.8) |
| Non-specific | ||||||
| Had ≥ 1 dispensation, n (%) | 30,976 (56.1) | 26,737 (48.4) | −7.7 (−7.1;−8.3) | 28,133 (57.6) | 24,124 (49.4) | −8.2 (−8.6;−7.8) |
| Number of days supplied | ||||||
| Mean (SD) | 282.1 (242.0) | 306.8 (223.9) | 281.6 (218.3) | 281.6 (218.3) | ||
| Median (Q1-Q3) | 210 (90–400) | 300 (120–390) | 270.0 (90.0–390.0) | 270.0 (90.0–390.0) | ||
| By class, n (%) | ||||||
| Antidepressants | 8,310 (15.1) | 6,760 (12.2) | −2.8 (−3.1;−2.5) | 7,475 (15.3) | 6,035 (12.4) | −2.9 (−3.3;−2.6) |
| Antiepileptics | 8,864 (16.1) | 8,913 (16.1) | 0.1 (−0.2;0.4) | 8,008 (16.4) | 8,048 (16.5) | 0.1 (−0.2;0.4) |
| Antihypertensives | 13,802 (25.0) | 11,064 (20.0) | −5.0 (−5.3;−4.7) | 12,650 (25.9) | 10,041 (20.6) | −5.3 (−5.7;−5.0) |
| OnabotulinumtoxinA | ||||||
| Had ≥ 1 procedure, n (%) | 8,478 (15.4) | 8,169 (14.8) | −0.6 (−1.0;−0.2) | 7,596 (15.6) | 7,210 (14.8) | −0.8 (−1.1;−0.5) |
| Number of procedures | ||||||
| Mean (SD) | 3.0 (1.3) | 2.9 (1.3) | 3.0 (1.3) | 2.8 (1.3) | ||
| Median (Q1-Q3) | 3 (2–4) | 3 (2–4) | 3.0 (2.0–4.0) | 3.0 (2.0–4.0) | ||
Abbreviations: CGRP Calcitonin Gene-Related Peptide, mAB monoclonal antibodies, NE Not Estimated, SD Standard Deviation, Q1-Q3 First and Third quartiles
*Includes erenumab, fremanezumab, galcanezumab, and eptinezumab
† Based on the earliest dispensation date of a CGRP inhibitor medication† Based on the earliest dispensation date of a CGRP inhibitor medication
†† Based on the earliest dispensation date of a mAB medication.† Based on the earliest dispensation date of a mAB medication
The analysis of migraine-related healthcare encounters (including hospitalizations, ambulatory visits, ED visits, and outpatient physician visits) revealed a significant decline in the proportion of individuals with at least one healthcare visit from the one-year pre-index to the post-index interval (Table 4). Specifically, the percentage of users who had any migraine-related healthcare encounter decreased from 81.0% to 68.2% (difference: −12.8% from post to pre-index intervals; 95% CI: −13.2% to −12.3%).
Table 4.
Pre- and post- migraine-related healthcare encounters in calcitonin gene-related peptide (CGRP) inhibitor users, MarketScan, US, 2018–2022
| CGRP inhibitor users n = 55,212 | mAB* users n = 48,834 | |||||
|---|---|---|---|---|---|---|
| One-year Pre-index date† | One-year Post-index date† | Difference (95% CI) | One-year Pre-index date†† | One-year Pos-tindex date†† | Difference (95% CI) |
|
| Any migraine-related healthcare encounter | ||||||
| Had ≥ 1 visit, n (%) | 44,701 (81.0) | 37,662 (68.2) | −12.8 (−13.2;−12.3) | 40,463 (82.9) | 34,375 (70.4) | −12.5 (−12.9;−12.0) |
| Number of visits | ||||||
| Mean (SD) | 3.5 (3.7) | 3.3 (3.8) | 3.6 (3.8) | 3.3 (3.9) | ||
| Median (Q1-Q3) | 3 (1–4) | 2 (1–4) | 3.0 (2.0–5.0) | 2.0 (1.0–4.0) | ||
| Migraine-related hospitalizations | ||||||
| Had ≥ 1 visit, n (%) | 301 (0.6) | 213 (0.4) | −0.2 (−0.2;−0.2) | 285 (0.6) | 207 (0.4) | −0.2 (−0.1; −0.2) |
| Length of hospital stay (day) | ||||||
| Mean (SD) | 4.6 (4.5) | 4.8 (4.2) | 4.7 (4.6) | 4.8 (4.3) | ||
| Median (Q1-Q3) | 3 (2–6) | 3 (2–6) | 3.0 (2.0–6.0) | 3.0 (2.0–6.0) | ||
| Migraine-related ED visits | ||||||
| Had ≥ 1 visit, n (%) | 4,582 (8.3) | 3,077 (5.6) | −2.7 (−2.9;−2.5) | 4,233 (8.7) | 2,864 (5.9) | −2.8 (−3.1;−2.5) |
| Number of visits | ||||||
| Mean (SD) | 1.7 (2.6) | 1.8 (3.0) | 1.7 (2.7) | 1.8 (3.1) | ||
| Median (Q1-Q3) | 1 (1–2) | 1 (1–2) | 1.0 (1.0–2.0) | 1.0 (1.0–2.0) | ||
| Migraine-related ambulatory care visits | ||||||
| Had ≥ 1 visit, n (%) | 11,383 (20.6) | 9,540 (17.3) | −3.3 (−3.7;−3.0) | 10,435 (21.4) | 8,774 (18.0) | −3.4 (−3.8;−3.0) |
| Number of visits | ||||||
| Mean (SD) | 2.2 (3.2) | 2.2 (3.3) | 2.2 (3.2) | 2.2 (3.3) | ||
| Median (Q1-Q3) | 1 (1–2) | 1 (1–2) | 1.0 (1.0–2.0) | 1.0 (1.0–2.0) | ||
| Migraine-related outpatient physician visits | ||||||
| Had ≥ 1 visit, n (%) | 42,573 (77.1) | 35,001 (63.4) | −13.7 (−14.1; −13.3;) | 38,655 (79.2) | 32,024 (65.6) | −13.6 (−14.0;−13.1) |
| Number of visits | ||||||
| Mean (SD) | 3.0 (2.5) | 2.8 (2.6) | 3.0 (2.5) | 2.8 (2.7) | ||
| Median (Q1-Q3) | 2 (1–4) | 2 (1–3) | 2.0 (1.0–4.0) | 2.0 (1.0–4.0) | ||
Abbreviations: CGRP Calcitonin Gene-Related Peptide, mAB monoclonal antibodies, SD Standard Deviation, Q1-Q3 First and Third quartile
*Includes erenumab, fremanezumab, galcanezumab, and eptinezumab
† Based on the earliest dispensation date of a CGRP inhibitor medication
†† Based on the earliest dispensation date of a mAB medication
Findings from the mAb-only subgroup analyses were consistent with those observed in the overall CGRP cohort, reflecting the fact that most users in our study were prescribed monoclonal antibodies rather than gepants. Given the recent approval of gepants for preventive use, their contribution to the cohort was smaller and limited to more recent years (2021–2022), with rimegepant representing the main agent in this group.
Discussion
We provide real-world insights into treatment patterns and healthcare use among individuals initiating CGRP inhibitors. The results describe the evolving landscape of CGRP inhibitor use. The main findings include: (i) a consistent increase in CGRP inhibitor use over the study period, (ii) a low frequency of switching between CGRP agents, particularly within the first year of initiation, and (iii) a reduction in the use of other migraine-related medications and healthcare encounters following CGRP initiation.
Across time, stratified analyses show the highest use occurred in females and individuals aged 45–64 years (which represents the demographics of individuals with migraine) [23]. One recently published paper showed a consistent uptake of CGRP inhibitor use when compared with other migraine medications [24]. However, our study provides more recent data and offers additional insights by examining trends for individual CGRP inhibitors rather than focusing solely on the class. In terms of specific CGRP inhibitors, we saw a decrease in erenumab use over time, coupled with an increase in galcanezumab and fremanezumab. Pricing, reimbursement policies and patient preferences may have influenced the dispensing patterns observed in our study. Erenumab, the first CGRP-targeted mAb approved in the US (May 2018), was launched at a list price of US $575/month (~ US $6,900/year) [25]. Galcanezumab and fremanezumab, approved shortly thereafter (September 2018), entered the market at comparable list and net prices to erenumab but offer patient-preferred features, such as quarterly dosing (fremanezumab [26]) and robust patient copay assistance programs that often reduced out-of-pocket costs for eligible commercial insurance patients [25]. The gradual uptake of alternative options over time may also reflect responses of the physician or patient to inadequate response and/or intolerance to an initial CGRP inhibitor, in the hopes that another agent in the same class might provide more benefit or be better tolerated. The increased use of rimegepant may be attributed to its amended approval for preventive use (May 2021) and its convenient oral administration, compared to the injectable forms of other CGRP inhibitors.
During the first year, 10.3% of individuals switched from their initial CGRP inhibitor to a second agent. These findings complement prior clinical studies, which have reported the safety and effectiveness of switching between CGRP inhibitors, for patients experiencing adverse effects or inadequate symptom control [27–29]. Unlike these smaller clinical studies, our analysis leverages a large, real-world claims database, offering a broader perspective on switching patterns over time. While we were unable to assess migraine symptom changes after switching due to the limitations of the data, we quantified switching rates and compared patterns across individual CGRP inhibitors, offering valuable insights into real-world prescribing trends and long-term treatment dynamics.
Our findings also indicate that 10.2% of CGRP inhibitor users transitioned to onabotulinumtoxinA injections within the first year, while 30.4% switched to other migraine prophylactics, such as antidepressants or antihypertensives (e.g., beta-blockers) in the same period. Among CGRP inhibitors, eptinezumab had the highest transition rate to onabotulinumtoxinA (15.6%), while erenumab had the highest transition rate to onabotulinumtoxinA (10.7%) among the three most used CGRP inhibitors. We speculate that these trends indicate that CGRP inhibitors alone may not provide sufficient relief for all patients, necessitating a switch or the addition of alternative therapies. In 5.1% of cases, patients used both CGRP inhibitors and onabotulinumtoxinA within the first year, highlighting the potential role of combination therapies, which have been shown to enhance treatment effectiveness [30].
Regarding discontinuation, 13.5% of patients ceased CGRP treatment in the first year. When accounting for varying follow-up durations, the probability of discontinuation was 15.7% and 29.3% within the first and second years, respectively. Potential reasons for discontinuation may include lack of effectiveness, intolerance to treatment, or changes in drug coverage. These rates appear lower than those observed in other studies, which may be attributed to differences in methodological design, such as the allowance for treatment gaps [31]. The median time to first discontinuation was approximately 4.3 years, indicating that CGRP inhibitors can provide relatively long-term relief for many, although the high substantial loss to follow-up inherent to the claims-based data used limits conclusions somewhat.
We showed a reduction in migraine-related medications and healthcare use after CGRP inhibitor initiation. These results align with previous studies [32–34]. However, most prior research has focused exclusively on erenumab, limiting generalizability to other CGRP inhibitors. Estimating direct economic impact was beyond the scope of this study, but this reduction might have real cost implications. For example, a US claims data analysis indicated that CGRP-monoclonal antibody users experienced significant reductions in migraine‐related medical costs (~ US $3,301) and outpatient acute medication costs (~ US $1,558) compared to standard‐of‐care users (~ US $2,279 and ~$1,200, respectively) [35].
Additionally, in our study, a significant proportion of CGRP inhibitor initiators also used onabotulinumtoxinA (15%), antidepressants (25%), antiepileptics (33%), and antihypertensives (41%). This suggests the potential benefit of combination therapy for managing migraine, at least in some patients [36]. Despite reductions in migraine-related medication use in the year after CGRP inhibitor initiation, dispensations of acute non-specific (e.g.: opioids) or migraine-specific medications (e.g.: triptan) remained high. In particularly, the use of gepants increased in the post-index intervals. This likely reflects residual migraine attacks, prompting healthcare providers to prescribe these medications as abortive options when other treatments fail or are contraindicated.
Strengths and potential limitations
The main strengths of this study include its large sample size and the ability to track healthcare use. We were also able to assess calendar year trends in CGRP inhibitor use, particularly as new agents emerged.
Potential limitations should be considered. First, the study population is specific to insured individuals in the US. As with all administrative health care databases, we had information only on medication dispensations, not actual drug consumption. This is especially relevant in assessing acute medication use, which could reflect a desire to keep backup supplies available, potentially underestimating the effectiveness of CGRP inhibitors. Furthermore, the database does not indicate the intended use of medications. For example, anti-depressants could be used for migraine prophylaxis, mood disorders, or other indications. The lack of information on the reason for prescribing posed a particular challenge when assessing the prophylactic use of rimegepant. In the US, rimegepant was approved exclusively as an acute medication until 2021, when it also gained approval for prophylactic use. After this date, there is no direct way, using claim data, to differentiate whether a rimegepant dispense was for acute or prophylactic purposes. Our approach was to consider it as prophylactic only when the dispensation record had a supply of 30 days or more. Given this limitation, some rimegepant acute use may have been misclassified as prophylactic, which could partially explain the high switching rate observed for this medication. Insurance-driven discontinuations, particularly due to changes in drug coverage, could also influence switching/discontinuation assessments. The study’s reliance on claims data also misses over-the-counter use of NSAIDs and/or acetaminophen to abort migraine. Despite these potential limitations, our study offers valuable insights for physicians, patients, and policymakers, and provides a foundation for further investigation into treatment trends and outcomes in real-world settings.
In conclusion, CGRP inhibitors demonstrated increasing use over time, with about 10% switching between CGRP agents (particularly within the first year of initiation). We saw reductions in other migraine-related medications and physician/ED visits following CGRP initiation. As new agents emerge, additional analyses will be needed to understand the long-term effectiveness and optimal use of CGRP inhibitors and other preventive treatments in real-world settings. From a health policy perspective, the costs of CGRP inhibitors need to be considered in relation to their potential to reduce healthcare utilization and associated expenses.
Supplementary Information
Acknowledgements
The authors would like to thank analysts Zhaoyu Liu, Karen Martins, Khanh Vu and Houssem Missaoui for their contributions to the development of the study protocol, interpretation of findings and review of the report. We thank Dr. Sarah Treit for her valuable contributions to this study, particularly for her expertise and assistance in preparing the Sankey diagram. We also thank Autumn Neville for her valuable support throughout the research and manuscript preparation stages.
Abbreviations
- CGRP inhibitors
Calcitonin gene-related peptide inhibitors
- ED
Emergency department
- CI
Confidence interval
- US
United States
- NSAIDs
Non-steroidal anti-inflammatory drugs
- mAbs
Monoclonal antibodies
- HIPAA
Health Insurance Portability and Accountability Act
- NDC
National Drug Code
- HSPCS
Healthcare Common Procedure Coding System
- SD
Standard deviations
- Q1-Q3
First and third quartiles
- Gepant
Small-Molecule CGRP Receptor Antagonists
Authors’ contributions
CSM, JRR, SK, J-LK, and SB contributed to the conception and design of the study; SB acquired the data; CSM, JRR, SK, HB, J-LK, HL, and SB contributed to analysis of data; CSM, JRR, SK, HB, HL, FA, J-LK, and SB contributed to drafting the text and preparing the figures. All authors copy edited and approved the final draft.
Funding
This work was supported by Canada’s Drug Agency (CDA-AMC) and its Post-Market Drug Evaluation Program through funding provided by Health Canada.
Data availability
This study used third-party data available through a licensing agreement and cannot be shared by the authors. Requests to access the data should be directed to the US Merative MarketScan® Research Databases. The analysis code is available upon request from the authors. Data were used in compliance with privacy and confidentiality requirements.
Declarations
Ethics approval and consent to participate
The study was approved by the Research Ethics Office of the Faculty of Medicine, McGill University (IRB Study Number A04-M47-12B). Informed consent is not applicable because the study used de-identified claims data.
Consent for publication
Not applicable.
Competing interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this manuscript: JRR, HL, 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). FA reports receiving research support from Eli Lilly, Allergan/Abbvie, Biohaven, Novartis, and Teva; consulting fees from Eli Lilly, Novartis, Teva, Lundbeck, ICEBM, and Pfizer; and speaker honoraria from Eli Lilly, Novartis, Teva, Allergan/Abbvie, ICEBM, and Aralez. All other authors report no conflict.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Ashina M, Katsarava Z, Do TP, Buse DC, Pozo-Rosich P, Özge A, Krymchantowski AV, Lebedeva ER, Ravishankar K, Yu S, Sacco S, Ashina S, Younis S, Steiner TJ, Lipton RB (2021) Migraine: epidemiology and systems of care. Lancet 397:1485–1495. 10.1016/S0140-6736(20)32160-7 [DOI] [PubMed] [Google Scholar]
- 2.Safiri S, Pourfathi H, Eagan A, Mansournia MA, Khodayari MT, Sullman MJM, Kaufman J, Collins G, Dai H, Bragazzi NL, Kolahi A-A (2022) Global, regional, and national burden of migraine in 204 countries and territories, 1990 to 2019. Pain 163:e293–e309. 10.1097/j.pain.0000000000002275 [DOI] [PubMed] [Google Scholar]
- 3.Burch R, Rizzoli P, Loder E (2018) The prevalence and impact of migraine and severe headache in the United States: figures and trends from government health studies. Headache 58:496–505. 10.1111/head.13281 [DOI] [PubMed] [Google Scholar]
- 4.Cohen F, Brooks CV, Sun D, Buse DC, Reed ML, Fanning KM, Lipton RB (2024) Prevalence and burden of migraine in the United States: a systematic review. Headache 64:516–532. 10.1111/head.14709 [DOI] [PubMed] [Google Scholar]
- 5.Graves EB, Gerber BR, Berrigan PS, Shaw E, Cowling TM, Ladouceur M-P, Bougie JK (2022) Epidemiology and treatment utilization for Canadian patients with migraine: a literature review. J Int Med Res 50:3000605221126380. 10.1177/03000605221126380 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ramage-Morin PL, Gilmour H (2014) Prevalence of migraine in the Canadian household population. Health Rep 25:10–16 [PubMed] [Google Scholar]
- 7.Bonafede M, Sapra S, Shah N, Tepper S, Cappell K, Desai P (2018) Direct and indirect healthcare resource utilization and costs among migraine patients in the united States. Headache 58:700–714. 10.1111/head.13275 [DOI] [PubMed] [Google Scholar]
- 8.Migraine | National Institute of Neurological Disorders and Stroke https://www.ninds.nih.gov/health-information/disorders/migraine. Accessed 5 Nov 2024
- 9.Puledda F, Silva EM, Suwanlaong K, Goadsby PJ (2023) Migraine: from pathophysiology to treatment. J Neurol 270:3654–3666. 10.1007/s00415-023-11706-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Wrobel Goldberg S, Silberstein SD (2015) Targeting CGRP: a new era for migraine treatment. CNS Drugs 29:443–452. 10.1007/s40263-015-0253-z [DOI] [PubMed] [Google Scholar]
- 11.Huang I-H, Wu P-C, Lin E-Y, Chen C-Y, Kang Y-N (2019) Effects of anti-calcitonin gene-related peptide for migraines: a systematic review with meta-analysis of randomized clinical trials. Int J Mol Sci 20:3527. 10.3390/ijms20143527 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Scuteri D, Adornetto A, Rombolà L, Naturale MD, Morrone LA, Bagetta G, Tonin P, Corasaniti MT (2019) New trends in migraine pharmacology: targeting calcitonin gene-related peptide (CGRP) with monoclonal antibodies. Front Pharmacol 10:363. 10.3389/fphar.2019.00363 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Charles AC, Digre KB, Goadsby PJ, Robbins MS, Hershey A, American Headache Society (2024) calcitonin gene-related peptide-targeting therapies are a first-line option for the prevention of migraine: an American Headache Society position statement update. Headache 64:333–341. 10.1111/head.14692 [DOI] [PubMed]
- 14.Medrea I, Cooper P, Langman M, Sandoe CH, Amoozegar F, Hussain WM, Bradi AC, Dawe J, Guay M, Perreault F, Reid S, Todd C, Skidmore B, Christie SN (2024) Updated Canadian headache society migraine prevention guideline with systematic review and Meta-analysis. Can J Neurol Sci J Can Sci Neurol 1–23. 10.1017/cjn.2024.285 [DOI] [PubMed]
- 15.Canadian Agency for Drugs and Technologies in Health (CADTH) (2020) CADTH Canadian drug expert committee recommendation: erenumab (Aimovig). Canadian Agency for Drugs and Technologies in Health (CADTH) [PubMed]
- 16.Canadian Agency for Drugs and Technologies in Health (CADTH) (2021) CADTH reimbursement recommendation: emgality (Galcanezumab). Canadian Agency for Drugs and Technologies in Health (CADTH)
- 17.Musial L, Kheloussi S (2023) Prior authorization requirements for calcitonin gene-related peptide antagonists. Am J Manag Care 29:e117–e123. 10.37765/ajmc.2023.89352 [DOI] [PubMed] [Google Scholar]
- 18.Varnado OJ, Manjelievskaia J, Ye W, Perry A, Schuh K, Wenzel R (2022) Treatment patterns for calcitonin gene-related peptide monoclonal antibodies including galcanezumab versus conventional preventive treatments for migraine: a retrospective US claims study. Patient Prefer Adherence 16:821–839. 10.2147/PPA.S346660 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Canadian Agency for Drugs and Technologies in Health (CADTH) (2023) CADTH health technology assessment report: HC0081. Canadian Agency for Drugs and Technologies in Health (CADTH)
- 20.MarketScan Research Databases for life sciences researchers https://www.merative.com/content/dam/merative/documents/brief/marketscan-research-databases-for-life-sciences-researchers.pdf. Accessed 20 Nov 2024
- 21.Ailani J, Lewis M, Dai F, Jenkins A, Cirillo J, Hygge Blakeman K, Abraham L, Brown J (2024) Evaluation of rimegepant utilization patterns and patient characteristics among new users: a united States administrative claims-based study. Curr Med Res Opin 40:1913–1920. 10.1080/03007995.2024.2410930 [DOI] [PubMed] [Google Scholar]
- 22.Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi J-C, Saunders LD, Beck CA, Feasby TE, Ghali WA (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130–1139. 10.1097/01.mlr.0000182534.19832.83 [DOI] [PubMed] [Google Scholar]
- 23.Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C (2020) Gender-related differences in migraine. Neurol Sci 41:429–436. 10.1007/s10072-020-04643-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Nguyen JL, Munshi K, Peasah SK, Swart ECS, Kohli M, Henderson R, Good CB (2022) Trends in utilization and costs of migraine medications, 2017–2020. J Headache Pain 23:111. 10.1186/s10194-022-01476-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Bucklan J, Ahmed Z (2020) CGRP antagonists for decreasing migraine frequency: new options, long overdue. Cleve Clin J Med 87:211–218. 10.3949/ccjm.87a.19048 [DOI] [PubMed] [Google Scholar]
- 26.Buse DC, Gandhi SK, Cohen JM, Ramirez-Campos V, Cloud B, Yang R, Cowan RP (2020) Improvements across a range of patient-reported domains with fremanezumab treatment: results from a patient survey study. J Headache Pain. 10.1186/s10194-020-01177-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Youn MS, Kim N, Lee MJ, Kim M (2024) Treatment outcome after switching from galcanezumab to fremanezumab in patients with migraine. J Clin Neurol Seoul Korea 20:300–305. 10.3988/jcn.2023.0311 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Suliman R, Santos V, Al Qaisi I, Aldaher B, Al Fardan A, Al Barrawy H, Bader Y, Supena JL, Alejandro K, Alsaadi T (2024) Effectiveness of switching CGRP monoclonal antibodies in non-responder patients in the UAE: a retrospective study. Neurol Int 16:274–288. 10.3390/neurolint16010019 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Overeem LH, Peikert A, Hofacker MD, Kamm K, Ruscheweyh R, Gendolla A, Raffaelli B, Reuter U, Neeb L (2022) Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine: a multi-center retrospective cohort study. Cephalalgia 42:291–301. 10.1177/03331024211048765 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Scuteri D, Tonin P, Nicotera P, Vulnera M, Altieri GC, Tarsitano A, Bagetta G, Corasaniti MT (2022) Pooled analysis of real-world evidence supports anti-CGRP mAbs and OnabotulinumtoxinA combined trial in chronic migraine. Toxins 14:529. 10.3390/toxins14080529 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Varnado OJ, Brady BL, Zagar AJ, Robles YP, Hoyt M (2024) Comparison of treatment patterns in patients with migraine initiating calcitonin gene-related peptide monoclonal antibodies: a retrospective real-world US study. Patient Prefer Adherence 18:69–88. 10.2147/PPA.S437396 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Tepper SJ, Fang J, Vo P, Shen Y, Zhou L, Abdrabboh A, Glassberg M, Ferraris M (2021) Impact of erenumab on acute medication usage and health care resource utilization among migraine patients: a US claims database study. J Headache Pain 22:27. 10.1186/s10194-021-01238-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Chandler D, Szekely C, Aggarwal S, Cyprien L, Bensink M (2021) Migraine characteristics, comorbidities, healthcare resource utilization, and associated costs of early users of erenumab in the USA: a retrospective cohort study using administrative claims data. Pain Ther 10:1551–1566. 10.1007/s40122-021-00319-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Urman R, Princic N, Vuvu F, Patel LB, Oh S, Chandler D, Hindiyeh N, Bensink ME (2024) Changes in use of migraine medications, healthcare resource utilization, and associated direct costs over 12 months following initiation of erenumab: a US retrospective real-world analysis. Pain Ther 13:1299–1313. 10.1007/s40122-024-00644-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Varnado OJ, Manjelievskaia J, Ye W, Perry A, Schuh K, Wenzel R (2022) Health care resource utilization and costs associated with treatment among patients initiating calcitonin gene-related peptide inhibitors vs other preventive migraine treatments in the united States. J Manag Care Spec Pharm 28:818–829. 10.18553/jmcp.2022.28.8.818 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Ailani J, Blumenfeld AM (2022) Combination CGRP monoclonal antibody and OnabotulinumtoxinA treatment for preventive treatment in chronic migraine. Headache 62:106–108. 10.1111/head.14244 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
This study used third-party data available through a licensing agreement and cannot be shared by the authors. Requests to access the data should be directed to the US Merative MarketScan® Research Databases. The analysis code is available upon request from the authors. Data were used in compliance with privacy and confidentiality requirements.