Persistence, Switching, and Healthcare Use after Initiating Calcitonin Gene-Related Peptide Inhibitors: A Real-world Assessment

Persistence, Switching, and Healthcare Use after Initiating Calcitonin Gene-Related Peptide Inhibitors: A Real-world Assessment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Persistence, Switching, and Healthcare Use after Initiating Calcitonin Gene-Related Peptide Inhibitors: A Real-world Assessment Cristiano S Moura, Jason R Randall, Scott Klarenbach, Hassan Behlouli, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7013231/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Dec, 2025 Read the published version in The Journal of Headache and Pain → Version 1 posted 10 You are reading this latest preprint version 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 United States Merative™ MarketScan® Research data to identify adults using CGRP inhibitors 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. Results: We studied 148,100 individuals 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 13.5% discontinued their first CGRP inhibitor. Post-initiation, the proportion of individuals with migraine-related medication use decreased by 4.5% (95% confidence interval, CI: 4.0%-4.9%), and healthcare use declined by 12.8% (95% CI: 12.3%-13.2%). Conclusions: CGRP inhibitors demonstrated increasing use over time, low frequency of switching between CGRP agents (particularly within the first year of initiation) and reduction in other migraine-related medications and physician/ED visits following CGRP initiation. Trial Registration: N/A migraine calcitonin gene-related peptide inhibitors treatment patterns administrative data Figures Figure 1 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 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 [15]. 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 [16]. Methods Design and data source We conducted a retrospective cohort study using the US Merative TM 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 [17]. 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. 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 [18] (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 pre- and post-intervals were calculated, along with their 95% confidence intervals (95% CI). Results We studied 148,100 unique individuals (median patient enrollment duration: 403 days; Q1-Q3: 185–795) with at least one dispensation of CGRP inhibitor between 2018 and 2022 (85.9% female; mean age: 43.1 years, SD: 12.3). 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 that 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) 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) CGRP = Calcitonin Gene-Related Peptide * 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, 10.3% of the 73,258 initiators switched to another 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) inhibitor users 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 N= 73,258 38,385 17,263 3,477 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) CGRP = Calcitonin Gene-Related Peptide 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 in the pre-index interval was 93.2%, compared to 88.7% in the post-index interval, reflecting a reduction of 4.5% (95% CI: 4.0%-4.9%). 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 opioids, which slightly increased in the post-index interval (46.6% vs. 44.3%, difference: -2.3%, 95% CI: -3.1% to -1.5%) and gepants (13.9% vs. 21.2%, difference: -7.3%, 95% CI: -7.9% to -6.7%). 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 One-year Pre-index One-year Post-index * Difference (95% CI) Any migraine-related medication Had ≥ 1 dispensation, n (%) 51,435 (93.2) 48,992 (88.7) 4.5 (4.0;4.9) Acute medications, overall Had ≥ 1 dispensation, n (%) 47,614 (86.2) 44,232 (80.1) 6.1 (5.7;6.5) Number of days supplied Mean (SD) 162.5 (168.7) 159.0 (171.3) Median (Q1-Q3) 101 (35–240) 94 (30–240) Non-specific acute medications Had ≥ 1 dispensation, n (%) 30,772 (55.7) 28,970 (52.5) 3.2 (2.6;3.8) By class, n (%) NSAIDs 17,153 (55.7) 15,467 (53.4) 2.3 (1.5;3.1) Opioids 13,619 (44.3) 13,503 (46.6) -2.3 (-3.1;-1.5) Migraine-specific acute medications Had ≥ 1 dispensation, n (%) 37,223 (67.4) 32,435 (58.8) 8.6 (8.0;9.2) By class, n (%) Triptans 31,717 (85.2) 25,165 (77.6) 7.6 (7.0;8.2) Ergots 292 (0.8) 262 (0.8) 0.0 (-0.1;0.1) Ditans 31 (0.1) 124 (0.4) -0.3 (-0.4;0.2) Gepants 5,183 (13.9) 6,884 (21.2) -7.3 (-7.9;-6.7) Prophylactic medications, overall Had ≥ 1 dispensation, n (%) 34,313 (62.2) 30,151 (54.6) 7.6 (7.0;8.2) Non-specific Had ≥ 1 dispensation, n (%) 30,976 (56.1) 26,737 (48.4) 7.7 (7.1;8.3) Number of days supplied Mean (SD) 282.1 (242.0) 306.8 (223.9) Median (Q1-Q3) 210 (90–400) 300 (120–390) By class Antidepressants 8,310 (26.8) 6,760 (25.3) 1.5 (0.8;2.2) Antiepileptics 8,864 (28.6) 8,913 (33.3) 4.7 (3.9;5.5) Antihypertensives 13,802 (44.6) 11.064 (41.4) 3.2 (2.4;4.0) OnabotulinumtoxinA Had ≥ 1 procedure, n (%) 8,478 (15.4) 8,169 (14.8) 0.6 (0.2;1.0) Number of days supplied Mean (SD) 3.0 (1.3) 2.9 (1.3) Median (Q1-Q3) 3 (2–4) 3 (2–4) Abbreviations: CGRP = Calcitonin Gene-Related Peptide; NE: Not Estimated; SD = Standard Deviation; Q1-Q3 = First and Third quartiles * Based on the earliest dispensation date of a CGRP inhibitor 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 81.0–68.2% (difference in proportions of 12.8% from pre- to post-index intervals; 95% CI: 12.3%-13.2%). Table 4 Pre- and post- migraine-related healthcare encounters in CGRP inhibitor users, MarketScan, US, 2018–2022 CGRP inhibitor users N = 55,212 One-year Pre-index One-year Post-index * Difference (95% CI) Any migraine-related healthcare encounter Had ≥ 1 visit, n (%) 44,701 (81.0) 37,662 (68.2) 12.8 (12.3;13.2) Number of visits Mean (SD) 3.5 (3.7) 3.3 (3.8) Median (Q1-Q3) 3 (1–4) 2 (1–4) Migraine-related hospitalizations Had ≥ 1 visit, n (%) 301 (0.6) 213 (0.4) 0.2 (0.2;0.2) Length of hospital stay (day) Mean (SD) 4.6 (4.5) 4.8 (4.2) Median (Q1-Q3) 3 (2–6) 3 (2–6) Migraine-related ED visits Had ≥ 1 visit, n (%) 4,582 (8.3) 3,077 (5.6) 2.7 (2.5;2.9) Number of visits Mean (SD) 1.7 (2.6) 1.8 (3.0) Median (Q1-Q3) 1 (1–2) 1 (1–2) Migraine-related ambulatory care visits Had ≥ 1 visit, n (%) 11,383 (20.6) 9,540 (17.3) 3.3 (3.0;3.7) Number of visits Mean (SD) 2.2 (3.2) 2.2 (3.3) Median (Q1-Q3) 1 (1–2) 1 (1–2) Migraine-related outpatient physician visits Had ≥ 1 visit, n (%) 42,573 (77.1) 35,001 (63.4) 13.7 (13.3;14.1) Number of visits Mean (SD) 3.0 (2.5) 2.8 (2.6) Median (Q1-Q3) 2 (1–4) 2 (1–3) ; Abbreviations: CGRP = Calcitonin Gene-Related Peptide; SD = Standard Deviation; Q1-Q3 = First and Third quartile Based on the earliest dispensation date of a CGRP inhibitor medications 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) [ 19 ]. One recently published paper showed a consistent uptake of CGRP inhibitor use when compared with other migraine medications [ 20 ]. 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. This uptake of alternative options over time may 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. Increased uptake of rimegepant may be attributed to its amended approval for preventive use 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 [ 21 – 23 ]. 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 [ 24 ]. 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 [ 25 ]. 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 [ 26 – 28 ]. However, most prior research has focused exclusively on erenumab, limiting generalizability to other CGRP inhibitors. 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 [ 29 ]. 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. Abbreviations Calcitonin gene-related peptide inhibitors, CGRP inhibitors Emergency department, ED Confidence interval, CI United States, US Non-steroidal anti-inflammatory drugs, NSAIDs Monoclonal antibodies, mAbs Health Insurance Portability and Accountability Act, HIPAA National Drug Code, NDC Healthcare Common Procedure Coding System, HSPCS Standard deviations, SD First and third quartiles, Q1-Q3 Declarations Ethics approval 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 Availability of data and materials 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. 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. 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. Author 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. 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. References Ashina M, Katsarava Z, Do TP, et al (2021) Migraine: epidemiology and systems of care. Lancet Lond Engl 397:1485-1495. Safiri S, Pourfathi H, Eagan A, et al (2022) Global, regional, and national burden of migraine in 204 countries and territories, 1990 to 2019. Pain 163:e293-e309. 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. Graves EB, Gerber BR, Berrigan PS, et al (2022) Epidemiology and treatment utilization for Canadian patients with migraine: a literature review. J Int Med Res 50:3000605221126380. Cohen F, Brooks CV, Sun D, et al (2024) Prevalence and burden of migraine in the United States: A systematic review. Headache J Head Face Pain 64:516-532. Ramage-Morin PL, Gilmour H (2014) Prevalence of migraine in the Canadian household population. Health Rep 25:10-16. Bonafede M, Sapra S, Shah N, et al (2018) Direct and Indirect Healthcare Resource Utilization and Costs Among Migraine Patients in the United States. Headache 58:700-714. National Institute of Neurological Disorders and Stroke (2025) Migraine. https://www.ninds.nih.gov/health-information/disorders/migraine. Accessed 01 Feb 2025. Puledda F, Silva EM, Suwanlaong K, et al (2023) Migraine: from pathophysiology to treatment. J Neurol 270:3654-3666. Wrobel Goldberg S, Silberstein SD (2015) Targeting CGRP: A New Era for Migraine Treatment. CNS Drugs 29:443-452. Huang IH, Wu PC, Lin EY, et al (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. Scuteri D, Adornetto A, Rombolà L, et al (2019) New Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies. Front Pharmacol 10:363. Charles AC, Digre KB, Goadsby PJ, et al (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. Medrea I, Cooper P, Langman M, et al (2024) Updated Canadian Headache Society Migraine Prevention Guideline with Systematic Review and Meta-analysis. Can J Neurol Sci J. doi: 10.1017/cjn.2024.285. Varnado OJ, Manjelievskaia J, Ye W, et al (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.\ Randall JR, Luu H, Vu K, et al (2025) Calcitonin Gene-Related Peptide Inhibitors for Migraine Prophylaxis. Available via Canada’s Drug Agency - L’Agence des medicaments du Canada . https://www.cda-amc.ca/sites/default/files/hta-he/HC0081-Report.pdf Merative (2022) 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. Quan H, Sundararajan V, Halfon P, et al (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130-1139. Allais G, Chiarle G, Sinigaglia S, et al (2020) Gender-related differences in migraine. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol 41:429-436. Nguyen JL, Munshi K, Peasah SK, et al (2022) Trends in utilization and costs of migraine medications, 2017-2020. J Headache Pain 23:111. Youn MS, Kim N, Lee MJ, et al (2024) Treatment Outcome After Switching From Galcanezumab to Fremanezumab in Patients With Migraine. J Clin Neurol Seoul Korea 20:300-305. Suliman R, Santos V, Al Qaisi I, et al (2024) Effectiveness of Switching CGRP Monoclonal Antibodies in Non-Responder Patients in the UAE: A Retrospective Study. Neurol Int 16:274-288. Overeem LH, Peikert A, Hofacker MD, et al (2022) Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine: A multi-center retrospective cohort study. Cephalalgia Int J Headache 42:291-301. Scuteri D, Tonin P, Nicotera P, et al (2022) Pooled Analysis of Real-World Evidence Supports Anti-CGRP mAbs and OnabotulinumtoxinA Combined Trial in Chronic Migraine. Toxins 14:529. Varnado OJ, Brady BL, Zagar AJ, et al (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. Tepper SJ, Fang J, Vo P, et al (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. Chandler D, Szekely C, Aggarwal S, et al (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. Urman R, Princic N, Vuvu F, et al (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. Ailani J, Blumenfeld AM (2022) Combination CGRP monoclonal antibody and onabotulinumtoxinA treatment for preventive treatment in chronic migraine. Headache 62:106-108. Additional Declarations Competing interest reported. 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. Supplementary Files SupplementalMaterial.pdf Cite Share Download PDF Status: Published Journal Publication published 12 Dec, 2025 Read the published version in The Journal of Headache and Pain → Version 1 posted Editorial decision: Revision requested 08 Jul, 2025 Reviews received at journal 07 Jul, 2025 Reviewers agreed at journal 07 Jul, 2025 Reviews received at journal 06 Jul, 2025 Reviewers agreed at journal 06 Jul, 2025 Reviewers agreed at journal 04 Jul, 2025 Reviewers invited by journal 04 Jul, 2025 Editor assigned by journal 03 Jul, 2025 Submission checks completed at journal 03 Jul, 2025 First submitted to journal 30 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7013231","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":482357771,"identity":"9b02a569-4b56-4e15-8e6e-1592c4fd5701","order_by":0,"name":"Cristiano S Moura","email":"","orcid":"","institution":"The Research Institute of the McGill University Health Centre","correspondingAuthor":false,"prefix":"","firstName":"Cristiano","middleName":"S","lastName":"Moura","suffix":""},{"id":482357781,"identity":"a4015874-6916-4b57-928a-6d92e459e913","order_by":1,"name":"Jason R Randall","email":"","orcid":"","institution":"University of Alberta","correspondingAuthor":false,"prefix":"","firstName":"Jason","middleName":"R","lastName":"Randall","suffix":""},{"id":482357787,"identity":"37d73b48-178c-43b9-98f9-899da70c96af","order_by":2,"name":"Scott Klarenbach","email":"","orcid":"","institution":"University of Alberta","correspondingAuthor":false,"prefix":"","firstName":"Scott","middleName":"","lastName":"Klarenbach","suffix":""},{"id":482357789,"identity":"240c13d5-d3cb-48bb-8115-0400669b1d33","order_by":3,"name":"Hassan Behlouli","email":"","orcid":"","institution":"The Research Institute of the McGill University Health Centre","correspondingAuthor":false,"prefix":"","firstName":"Hassan","middleName":"","lastName":"Behlouli","suffix":""},{"id":482357790,"identity":"87c57f6f-64aa-421b-a9cd-1f1b926bf818","order_by":4,"name":"Huong Luu","email":"","orcid":"","institution":"University of 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17:53:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7013231/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7013231/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s10194-025-02167-0","type":"published","date":"2025-12-12T15:59:02+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86327543,"identity":"f2c006f9-eb07-4baa-b680-1fa493c4ab58","added_by":"auto","created_at":"2025-07-09 11:20:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":173539,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment trajectories in the first year of follow-up for individual CGRP inhibitors, MarketScan, US, 2018 – 2022.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7013231/v1/226b31fda1dc156a22f02cbd.jpg"},{"id":98244774,"identity":"bfc3760f-a8d8-49b2-94cd-78f7971c87b3","added_by":"auto","created_at":"2025-12-15 16:15:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1011618,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7013231/v1/af8ec144-910e-4b85-b54a-efb1ecc51598.pdf"},{"id":86328497,"identity":"37a2b520-d79d-444d-8273-5c6ed923aef0","added_by":"auto","created_at":"2025-07-09 11:28:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":111260,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalMaterial.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7013231/v1/86d15299c8b374dbd7199660.pdf"}],"financialInterests":"Competing interest reported. 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.","formattedTitle":"Persistence, Switching, and Healthcare Use after Initiating Calcitonin Gene-Related Peptide Inhibitors: A Real-world Assessment","fulltext":[{"header":"Background","content":"\u003cp\u003eMigraine 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].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe 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].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite the promise of CGRP inhibitors, their high cost necessitates careful formulary consideration of policies governing access 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 [15]. We aimed to describe real-world trends in the use of CGRP inhibitors, including treatment patterns, switching, discontinuation, and association with healthcare resource use. \u0026nbsp;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\u0026rsquo;s Drug Agency [16].\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eDesign and data source\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a retrospective cohort study using the US Merative\u003csup\u003eTM\u003c/sup\u003e MarketScan\u0026reg; 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 [17]. The database complies with the Health Insurance Portability and Accountability Act (HIPAA) to ensure patient privacy.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePopulation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe study included adult individuals (\u0026ge;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. 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).\u003c/p\u003e\n\u003cp\u003eBaseline 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.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStudy variables\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTrends 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\u0026nbsp;one, two, three-, and four-years post-initiation.\u0026nbsp;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\u0026rsquo; supply, or 90 days in the case of eptinezumab infusions or onabotulinumtoxinA injections. Overlaps of \u0026le;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.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA 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\u0026nbsp;with no additional dispensation or claim after the start of the new treatment. An overlap of \u0026le;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.\u0026nbsp;Concomitant use events (overlapping of \u0026ge;30 days between dispenses)\u0026nbsp;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 \u0026gt;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.\u003c/p\u003e\n\u003cp\u003eBaseline 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\u0026nbsp;[18] (Supplemental Table 3) and relevant comorbidities, such as cardiovascular disease, depression, anxiety, asthma, epilepsy, hypertension, and obstructive sleep apnea (Supplemental Table 4).\u003c/p\u003e\n\u003cp\u003eCharacteristics assessed for the one-year intervals before and after the index date included:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eUse of migraine-related medications, including acute and prophylactic therapies.\u003c/li\u003e\n \u003cli\u003eMigraine-related healthcare encounters, including hospitalizations, ED visits, ambulatory care, and outpatient physician visits (Supplemental Table 5).\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll 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.\u0026nbsp;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\u0026ndash;44, 45\u0026ndash;64, and 65+) and sex.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor 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.\u0026nbsp;Treatment trajectories in the first year were depicted using a Sankey diagram.\u003c/p\u003e\n\u003cp\u003eKaplan-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\u0026nbsp;study period\u0026apos;s end, whichever occurred first.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBaseline 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.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMigraine-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 pre- and post-intervals were calculated, along with their 95% confidence intervals (95% CI).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe studied 148,100 unique individuals (median patient enrollment duration: 403 days; Q1-Q3: 185\u0026ndash;795) with at least one dispensation of CGRP inhibitor between 2018 and 2022 (85.9% female; mean age: 43.1 years, SD: 12.3). 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\u0026nbsp;6.\u003c/p\u003e\n\u003cp\u003eThe prevalence of CGRP inhibitor use increased substantially from 2018 to 2022 (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). 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\u0026ndash;64 years, the demographics that 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.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eFrequency of Calcitonin Gene-Related Peptide (CGRP) Inhibitors use, MarketScan, US, 2018\u0026ndash;2022\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eCalendar year\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll CGRP, n (rate per 100,000 enrollees)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10,316 (46.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38,299 (187.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53,377 (278.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e69,440 (364.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82,624 (442.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBy age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u0026ndash;44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,638 (39.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18,578 (166.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26,048 (256.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34,512 (337.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40,895 (411.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45\u0026ndash;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,383 (60.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18,936 (229.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26,064 (342.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33,429 (453.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39,400 (558.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e295 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e785 (74.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,265 (88.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1,499 (102.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2,329 (137.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBy sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8,826 (77.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32,772 (307.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45,916 (459.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59,932 (604.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71,360 (730.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,490 (14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,527 (56.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7,461 (81.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9,508 (104.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11,264 (126.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBy agent, n (% of CGRP users)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eErenumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7,918 (76.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16,057 (42.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22,674 (42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,024 (33.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15,449 (18.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGalcanezumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e998 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13,966 (36.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21,274 (39.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,320 (33.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,338 (28.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFremanezumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,400 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8,276 (21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9,321(17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11,210 (16.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13,056 (15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEptinezumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e652 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e918 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAtogepant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e216 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6,427 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRimegepant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11,018 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23,436 (28.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eCGRP\u0026thinsp;=\u0026thinsp;Calcitonin Gene-Related Peptide\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003e Individuals on rimegepant were included as of May 27, 2021 onwards and only for dispenses with 30 or more days\u0026rsquo; supply\u003c/p\u003e\n\u003cp\u003eTreatment patterns of CGRP inhibitor users considering fixed follow-up duration are described in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. In the initial year of follow-up, 10.3% of the 73,258 initiators switched to another 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 \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;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. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) 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\u0026nbsp;7.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eTreatment patterns of Calcitonin Gene-Related Peptide (CGRP) inhibitor users across 1-, 2-, 3-, and 4-year fixed follow-up, MarketScan, US, 2018\u0026ndash;2022\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eFollow-up year\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInitial year\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOver 2-year follow-up\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOver 3-year follow-up\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOver 4-year follow-up\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN=\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73,258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38,385\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17,263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,477\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSwitching from an initial to a subsequent CGRP inhibitor, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7,537 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,077 (15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,668 (21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,224 (35.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSwitching from a CGRP inhibitor to onabotulinumtoxinA injection, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7,483 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,645 (12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,344 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e568 (16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSwitching from a CGRP inhibitor to non-specific migraine prophylactic treatment, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22,281 (30.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11,983 (31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,183 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e843 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcomitant CGRP inhibitor treatment and onabotulinumtoxinA injection, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,741 (5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,239 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,017 (11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e676 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcomitant use of CGRP inhibitor and non-migraine-specific prophylactic treatment, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10,069 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6,802 (17.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,466 (20.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e783 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTreatment break, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,301 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2,381 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,939 (11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e508 (14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiscontinuation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9,866 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,242 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1,971 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e215 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eCGRP\u0026thinsp;=\u0026thinsp;Calcitonin Gene-Related Peptide\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eWhen 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).\u003c/p\u003e\n\u003cp\u003eOverall, 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 \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). For example, the proportion of individuals with at least one dispensation of any migraine-related medication in the pre-index interval was 93.2%, compared to 88.7% in the post-index interval, reflecting a reduction of 4.5% (95% CI: 4.0%-4.9%). 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 opioids, which slightly increased in the post-index interval (46.6% vs. 44.3%, difference: -2.3%, 95% CI: -3.1% to -1.5%) and gepants (13.9% vs. 21.2%, difference: -7.3%, 95% CI: -7.9% to -6.7%).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMigraine-related medication use pre- and post-index among Calcitonin Gene-Related Peptide (CGRP) inhibitor users, MarketScan, US, 2018\u0026ndash;2022\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eCGRP inhibitor users n\u0026thinsp;=\u0026thinsp;55,212\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eOne-year Pre-index\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOne-year Post-index\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDifference (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAny migraine-related medication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 dispensation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51,435 (93.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e48,992 (88.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 (4.0;4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eAcute medications, overall\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 dispensation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47,614 (86.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e44,232 (80.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.1 (5.7;6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNumber of days supplied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e162.5 (168.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e159.0 (171.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101 (35\u0026ndash;240)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e94 (30\u0026ndash;240)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNon-specific acute medications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 dispensation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30,772 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e28,970 (52.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2 (2.6;3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBy class, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNSAIDs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17,153 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e15,467 (53.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.3 (1.5;3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eOpioids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13,619 (44.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e13,503 (46.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2.3 (-3.1;-1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMigraine-specific acute medications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 dispensation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37,223 (67.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e32,435 (58.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.6 (8.0;9.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBy class, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTriptans\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31,717 (85.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e25,165 (77.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.6 (7.0;8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eErgots\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e292 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e262 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0 (-0.1;0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDitans\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e124 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.3 (-0.4;0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eGepants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5,183 (13.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e6,884 (21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-7.3 (-7.9;-6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eProphylactic medications, overall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 dispensation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34,313 (62.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e30,151 (54.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.6 (7.0;8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNon-specific\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 dispensation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30,976 (56.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e26,737 (48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.7 (7.1;8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNumber of days supplied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e282.1 (242.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e306.8 (223.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e210 (90\u0026ndash;400)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e300 (120\u0026ndash;390)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eBy class\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAntidepressants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8,310 (26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e6,760 (25.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 (0.8;2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAntiepileptics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8,864 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e8,913 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.7 (3.9;5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAntihypertensives\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13,802 (44.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e11.064 (41.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2 (2.4;4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eOnabotulinumtoxinA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 procedure, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8,478 (15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e8,169 (14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6 (0.2;1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eNumber of days supplied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e2.9 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003e3 (2\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eAbbreviations: CGRP\u0026thinsp;=\u0026thinsp;Calcitonin Gene-Related Peptide; NE: Not Estimated; SD\u0026thinsp;=\u0026thinsp;Standard Deviation; Q1-Q3\u0026thinsp;=\u0026thinsp;First and Third quartiles\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e* Based on the earliest dispensation date of a CGRP inhibitor medication\u003c/p\u003e\n\u003cp\u003eThe 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 \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). Specifically, the percentage of users who had any migraine-related healthcare encounter decreased from 81.0\u0026ndash;68.2% (difference in proportions of 12.8% from pre- to post-index intervals; 95% CI: 12.3%-13.2%).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ctable id=\"Tab4\" border=\"1\" class=\"fr-table-selection-hover\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePre- and post- migraine-related healthcare encounters in CGRP inhibitor users, MarketScan, US, 2018\u0026ndash;2022\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eCGRP inhibitor users\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;55,212\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOne-year Pre-index\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOne-year Post-index\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDifference (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAny migraine-related healthcare encounter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 visit, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44,701 (81.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37,662 (68.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.8 (12.3;13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of visits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.5 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (1\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMigraine-related hospitalizations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 visit, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e301 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e213 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2 (0.2;0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength of hospital stay (day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.6 (4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMigraine-related ED visits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 visit, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4,582 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3,077 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (2.5;2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of visits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.8 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMigraine-related ambulatory care visits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 visit, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11,383 (20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9,540 (17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3 (3.0;3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of visits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1\u0026ndash;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMigraine-related outpatient physician visits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHad\u0026thinsp;\u0026ge;\u0026thinsp;1 visit, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42,573 (77.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35,001 (63.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.7 (13.3;14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of visits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (Q1-Q3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1\u0026ndash;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e; Abbreviations: CGRP\u0026thinsp;=\u0026thinsp;Calcitonin Gene-Related Peptide; SD\u0026thinsp;=\u0026thinsp;Standard Deviation; Q1-Q3\u0026thinsp;=\u0026thinsp;First and Third quartile\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eBased on the earliest dispensation date of a CGRP inhibitor medications\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe 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.\u003c/p\u003e\u003cp\u003eAcross time, stratified analyses show the highest use occurred in females and individuals aged 45\u0026ndash;64 years (which represents the demographics of individuals with migraine) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. One recently published paper showed a consistent uptake of CGRP inhibitor use when compared with other migraine medications [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. 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. This uptake of alternative options over time may 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. Increased uptake of rimegepant may be attributed to its amended approval for preventive use and its convenient oral administration, compared to the injectable forms of other CGRP inhibitors.\u003c/p\u003e\u003cp\u003eDuring 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 [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. 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.\u003c/p\u003e\u003cp\u003eOur 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 [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRegarding 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 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. 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.\u003c/p\u003e\u003cp\u003eWe showed a reduction in migraine-related medications and healthcare use after CGRP inhibitor initiation. These results align with previous studies [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, most prior research has focused exclusively on erenumab, limiting generalizability to other CGRP inhibitors. 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 [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eStrengths and potential limitations\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe 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.\u003c/p\u003e\u003cp\u003ePotential 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\u0026rsquo;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.\u003c/p\u003e\u003cp\u003eIn 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.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCalcitonin gene-related peptide inhibitors, CGRP inhibitors\u003c/p\u003e\n\u003cp\u003eEmergency department, ED\u003c/p\u003e\n\u003cp\u003eConfidence interval, CI\u003c/p\u003e\n\u003cp\u003eUnited States, US\u003c/p\u003e\n\u003cp\u003eNon-steroidal anti-inflammatory drugs, NSAIDs\u003c/p\u003e\n\u003cp\u003eMonoclonal antibodies, mAbs\u003c/p\u003e\n\u003cp\u003eHealth Insurance Portability and Accountability Act, HIPAA\u003c/p\u003e\n\u003cp\u003eNational Drug Code, NDC\u003c/p\u003e\n\u003cp\u003eHealthcare Common Procedure Coding System, HSPCS\u003c/p\u003e\n\u003cp\u003eStandard deviations, SD\u003c/p\u003e\n\u003cp\u003eFirst and third quartiles, Q1-Q3\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis 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\u0026reg; Research Databases. The analysis code is available upon request from the authors.\u0026nbsp;Data were used in compliance with privacy and confidentiality requirements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Canada\u0026rsquo;s Drug Agency (CDA-AMC) and its Post-Market Drug Evaluation Program through funding provided by Health Canada.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthor Contributions\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCSM, 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.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe 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.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAshina M, Katsarava Z, Do TP, et al (2021) Migraine: epidemiology and systems of care. Lancet Lond Engl 397:1485-1495.\u003c/li\u003e\n \u003cli\u003eSafiri S, Pourfathi H, Eagan A, et al (2022) Global, regional, and national burden of migraine in 204 countries and territories, 1990 to 2019. Pain 163:e293-e309.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBurch 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.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGraves EB, Gerber BR, Berrigan PS, et al (2022) Epidemiology and treatment utilization for Canadian patients with migraine: a literature review. J Int Med Res 50:3000605221126380.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCohen F, Brooks CV, Sun D, et al (2024) Prevalence and burden of migraine in the United States: A systematic review. Headache J Head Face Pain 64:516-532.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRamage-Morin PL, Gilmour H (2014) Prevalence of migraine in the Canadian household population. Health Rep 25:10-16.\u003c/li\u003e\n \u003cli\u003eBonafede M, Sapra S, Shah N, et al (2018) Direct and Indirect Healthcare Resource Utilization and Costs Among Migraine Patients in the United States. Headache 58:700-714.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eNational Institute of Neurological Disorders and Stroke (2025) Migraine. https://www.ninds.nih.gov/health-information/disorders/migraine. Accessed 01 Feb 2025.\u003c/li\u003e\n \u003cli\u003ePuledda F, Silva EM, Suwanlaong K, et al (2023) Migraine: from pathophysiology to treatment. J Neurol 270:3654-3666.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWrobel Goldberg S, Silberstein SD (2015) Targeting CGRP: A New Era for Migraine Treatment. CNS Drugs 29:443-452.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHuang IH, Wu PC, Lin EY, et al (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.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eScuteri D, Adornetto A, Rombol\u0026agrave; L, et al (2019) New Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies. Front Pharmacol 10:363.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCharles AC, Digre KB, Goadsby PJ, et al (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.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMedrea I, Cooper P, Langman M, et al (2024) Updated Canadian Headache Society Migraine Prevention Guideline with Systematic Review and Meta-analysis. Can J Neurol Sci J. doi: 10.1017/cjn.2024.285.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eVarnado OJ, Manjelievskaia J, Ye W, et al (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.\\\u003c/li\u003e\n \u003cli\u003eRandall JR, Luu H, Vu K, et al (2025) Calcitonin Gene-Related Peptide Inhibitors for Migraine Prophylaxis. Available via\u0026nbsp;\u003cem\u003eCanada\u0026rsquo;s Drug Agency - L\u0026rsquo;Agence des medicaments du Canada\u003c/em\u003e. https://www.cda-amc.ca/sites/default/files/hta-he/HC0081-Report.pdf\u003c/li\u003e\n \u003cli\u003eMerative (2022) MarketScan Research Databases for life sciences researchers. https://www.merative.com/content/dam/merative/documents/brief/marketscan-research-databases-for-life-sciences-researchers.pdf. 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Toxins 14:529.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eVarnado OJ, Brady BL, Zagar AJ, et al (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.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTepper SJ, Fang J, Vo P, et al (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.\u003c/li\u003e\n \u003cli\u003eChandler D, Szekely C, Aggarwal S, et al (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.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eUrman R, Princic N, Vuvu F, et al (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.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAilani J, Blumenfeld AM (2022) Combination CGRP monoclonal antibody and onabotulinumtoxinA treatment for preventive treatment in chronic migraine. Headache 62:106-108.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-journal-of-headache-and-pain","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tjhp","sideBox":"Learn more about [The Journal of Headache and Pain](https://thejournalofheadacheandpain.biomedcentral.com/)","snPcode":"10194","submissionUrl":"https://submission.nature.com/new-submission/10194/3","title":"The Journal of Headache and Pain","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"migraine, calcitonin gene-related peptide inhibitors, treatment patterns, administrative data","lastPublishedDoi":"10.21203/rs.3.rs-7013231/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7013231/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003eMigraine 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).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003eWe used the United States Merative™ MarketScan® Research data to identify adults using CGRP inhibitors 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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eWe studied 148,100 individuals 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 13.5% discontinued their first CGRP inhibitor. Post-initiation, the proportion of individuals with migraine-related medication use decreased by 4.5% (95% confidence interval, CI: 4.0%-4.9%), and healthcare use declined by 12.8% (95% CI: 12.3%-13.2%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eCGRP inhibitors demonstrated increasing use over time, low frequency of switching between CGRP agents (particularly within the first year of initiation) and reduction in other migraine-related medications and physician/ED visits following CGRP initiation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration:\u003c/strong\u003e N/A\u003c/p\u003e","manuscriptTitle":"Persistence, Switching, and Healthcare Use after Initiating Calcitonin Gene-Related Peptide Inhibitors: A Real-world Assessment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-09 11:20:15","doi":"10.21203/rs.3.rs-7013231/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-08T11:50:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-07T15:27:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"109500289141007673698707362307482553995","date":"2025-07-07T05:33:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-06T10:23:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"291704398482419532685976509164240645957","date":"2025-07-06T09:23:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"205705518943888029016097931693521798005","date":"2025-07-04T14:08:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-04T12:11:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-03T07:07:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-03T07:03:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Journal of Headache and Pain","date":"2025-06-30T17:47:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-journal-of-headache-and-pain","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tjhp","sideBox":"Learn more about [The Journal of Headache and Pain](https://thejournalofheadacheandpain.biomedcentral.com/)","snPcode":"10194","submissionUrl":"https://submission.nature.com/new-submission/10194/3","title":"The Journal of Headache and Pain","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dc02980c-fc75-4254-ab5e-ca035d99bb3d","owner":[],"postedDate":"July 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:08:59+00:00","versionOfRecord":{"articleIdentity":"rs-7013231","link":"https://doi.org/10.1186/s10194-025-02167-0","journal":{"identity":"the-journal-of-headache-and-pain","isVorOnly":false,"title":"The Journal of Headache and Pain"},"publishedOn":"2025-12-12 15:59:02","publishedOnDateReadable":"December 12th, 2025"},"versionCreatedAt":"2025-07-09 11:20:15","video":"","vorDoi":"10.1186/s10194-025-02167-0","vorDoiUrl":"https://doi.org/10.1186/s10194-025-02167-0","workflowStages":[]},"version":"v1","identity":"rs-7013231","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7013231","identity":"rs-7013231","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}